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1. Development and Validation of Prediction Models of Adverse Kidney Outcomes in the Population With and Without Diabetes

Author

Morgan E, Grams, Nigel J, Brunskill, Shoshana H, Ballew, Yingying, Sang, Josef, Coresh, Kunihiro, Matsushita, Aditya, Surapaneni, Samira, Bell, Juan J, Carrero, Gabriel, Chodick, Marie, Evans, Hiddo J L, Heerspink, Lesley A, Inker, Kunitoshi, Iseki, Philip A, Kalra, H Lester, Kirchner, Brian J, Lee, Adeera, Levin, Rupert W, Major, James, Medcalf, Girish N, Nadkarni, David M J, Naimark, Ana C, Ricardo, Simon, Sawhney, Manish M, Sood, Natalie, Staplin, Nikita, Stempniewicz, Benedicte, Stengel, Keiichi, Sumida, Jamie P, Traynor, Jan, van den Brand, Chi-Pang, Wen, Mark, Woodward, Jae Won, Yang, Angela Yee-Moon, Wang, Navdeep, Tangri, John, Chalmers, Chi-Yuan, Hsu, Amanda, Anderson, Panduranga, Rao, Harold, Feldman, Alex R, Chang, Kevin, Ho, Jamie, Green, Moneeza, Siddiqui, Colin, Palmer, Varda, Shalev, Marie, Metzger, Martin, Flamant, Pascal, Houillier, Jean-Philippe, Haymann, John, Cuddeback, Elizabeth, Ciemins, Csaba P, Kovesdy, Marco, Trevisan, Carl Gustaf, Elinder, Björn, Wettermark, Philip, Kalra, Rajkumar, Chinnadurai, James, Tollitt, Darren, Green, Ron T, Gansevoort, Orlando, Gutierrez, Tsuneo, Konta, Anna, Köttgen, Andrew S, Levey, Kevan, Polkinghorne, Elke, Schäffner, Luxia, Zhang, Jingsha, Chen, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Kidney Center (GKC)

Subjects
Advanced and Specialized Nursing, Endocrinology, Diabetes and Metabolism, Internal Medicine, Diabetes Mellitus, Albuminuria, Humans, Renal Insufficiency, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], Renal Insufficiency, Chronic, Kidney, Glomerular Filtration Rate
Abstract

OBJECTIVE To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design. RESEARCH DESIGN AND METHODS In this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; ≥60 or RESULTS There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts. CONCLUSIONS Novel prediction equations for a decline of ≥40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR.

Published
2022

2. New insights into acute-on-chronic kidney disease in nephrology patients: the CKD-REIN study

Author

Christian Combe, Jarcy Zee, Denis Fouque, Ziad A. Massy, Maurice Laville, Sophie Liabeuf, Céline Lange, Bruce G. Robinson, Carole Ayav, Luc Frimat, Marie Metzger, Bénédicte Stengel, Aghilès Hamroun, Chronic Kidney Disease-Renal Epidemiology, Yves-Edouard Herpe, François Glowacki, and Christian Jacquelinet

Subjects
Male, Nephrology, medicine.medical_specialty, medicine.medical_treatment, Renal function, urologic and male genital diseases, Cohort Studies, Renal Dialysis, Risk Factors, Internal medicine, Diabetes mellitus, medicine, Humans, Renal Insufficiency, Chronic, Dialysis, Aged, Transplantation, business.industry, Hazard ratio, Acute kidney injury, Acute Kidney Injury, medicine.disease, Kidney Failure, Chronic, Female, business, Glomerular Filtration Rate, Kidney disease, Cohort study
Abstract

Background Acute-on-chronic kidney disease (ACKD) is poorly understood and often overlooked. We studied its incidence, circumstances, determinants and outcomes in patients with CKD. Methods We used the Kidney Disease: Improving Global Outcomes criteria to identify all-stage acute kidney injury (AKI) events in 3033 nephrology outpatients with CKD Stages 3–5 participating in the CKD-Renal Epidemiology and Information Network cohort study (2013–20), and cause-specific Cox models to estimate hazard ratios [HRs; 95% confidence intervals (CIs)] of AKI-associated risk factors. Results At baseline, 22% of the patients [mean age 67 years, 65% men, mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] had a history of AKI. Over a 3-year follow-up, 443 had at least one AKI event: 27% were Stage 2 or 3 and 11% required dialysis; 74% involved hospitalization including 47% acquired as hospital inpatients; and a third were not reported in hospital discharge reports. Incidence rates were 10.1 and 4.8/100 person-years in patients with and without an AKI history, respectively. In 2375 patients without this history, male sex, diabetes, cardiovascular disease, cirrhosis, several drugs, low eGFR and serum albumin levels were significantly associated with a higher risk of AKI, as were low birth weight ( Conclusions The study highlights the high rate of hospital-acquired AKI events in patients with CKD, and their underreporting at hospital discharge. It also reveals low birth weight and anaemia as possible new risk factors in CKD patients.

Published
2021
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3. Urinary Sodium-to-Potassium Ratio and Blood Pressure in CKD

Author

Natalia Alencar de Pinho, Jean Kaboré, Maurice Laville, Marie Metzger, Céline Lange, Christian Jacquelinet, Christian Combe, Denis Fouque, Luc Frimat, Carol Ayav, Bruce M. Robinson, Tilman Drueke, Ziad A. Massy, Bénédicte Stengel, Thierry Hannedouche, Bruno Moulin, Sébastien Mailliez, Gaétan Lebrun, Eric Magnant, Gabriel Choukroun, Benjamin Deroure, Adeline Lacraz, Guy Lambrey, Jean Philippe Bourdenx, Marie Essig, Thierry Lobbedez, Raymond Azar, Hacène Sekhri, Mustafa Smati, Mohamed Jamali, Alexandre Klein, Michel Delahousse, Séverine Martin, Isabelle Landru, Eric Thervet, Philippe Lang, Xavier Belenfant, Pablo Urena, Carlos Vela, Dominique Chauveau, Viktor Panescu, Christian Noel, François Glowacki, Maxime Hoffmann, Maryvonne Hourmant, Dominique Besnier, Angelo Testa, François Kuentz, Philippe Zaoui, Charles Chazot, Laurent Juillard, Stéphane Burtey, Adrien Keller, Nassim Kamar, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Agence de la biomédecine [Saint-Denis la Plaine], Service de Néphrologie Transplantation, Dialyse et Aphérèse [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Arbor Research Collaborative for Health, Hôpital Ambroise Paré [AP-HP], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Agence Nationale de la Recherche, ANR Agence Nationale de la Recherche, ANR, The CKD-REIN study is funded by the Agence Nationale de la Recherche through the 2010 «Cohortes-Investissements d’Avenir » program (ANR) and by the 2010 national Programme Hospitalier de Recherche Clinique . CKD-REIN is also supported through a public–private partnership with Amgen , Fresenius Medical Care , and GlaxoSmithKline (GSK) since 2012, Lilly France since 2013, Otsuka Pharmaceutical since 2015, Baxter and Merck Sharp & Dohme-Chibret (MSD France) from 2012 to 2017, Sanofi-Genzyme from 2012 to 2015, and Vifor Fresenius and AstraZeneca , since 2018. Inserm Transfert set up and has managed this partnership since 2011., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Chronic Kidney Disease - Réseau Epidémiologie et Information en Néphrologie (CKD REIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Urinary system, Population, 030232 urology & nephrology, 030204 cardiovascular system & hematology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, Excretion, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Interquartile range, Internal medicine, medicine, salt, 10. No inequality, education, sodium, education.field_of_study, business.industry, potassium, blood pressure, medicine.disease, 3. Good health, Blood pressure, Quartile, Nephrology, Albuminuria, medicine.symptom, business, chronic kidney disease, Kidney disease
Abstract

Introduction In the general population, urinary sodium-to-potassium (uNa/K) ratio associates more strongly with high blood pressure (BP) than either urinary sodium or potassium alone. Whether this is also the case among patients with chronic kidney disease (CKD) is unknown. Methods We studied the associations of spot urine sodium-to-creatinine (uNa/Cr), potassium-to-creatinine (uK/Cr), and uNa/K ratios with a single office BP reading in 1660 patients with moderate to severe CKD at inclusion in the CKD-REIN cohort. Results Patients' median age was 68 (interquartile range [IQR], 59–76) years; most were men (65%), had moderate CKD (57%), and albuminuria (72%). Mean systolic and diastolic BP was 142/78 mm Hg. Spot uNa/Cr and uNa/K ratios were positively associated with systolic, mean arterial, and pulse pressures. The mean adjusted difference in systolic BP between the highest and the lowest quartile (Q4 vs. Q1) was 4.24 (95% confidence interval [CI], 1.53–6.96) mm Hg for uNa/Cr and 4.79 (95% CI, 2.18–7.39) mm Hg for uNa/K. Quartiles of spot uK/Cr were not associated with any BP index. The higher the quartile of uNa/K, the higher the prevalence ratio of uncontrolled (Q4 vs. Q1, 1.43; 95% CI, 1.19–1.72) or apparently treatment-resistant hypertension (Q4 vs. Q1, 1.35; 95% CI, 1.14–1.60). Findings were consistent in a subset of 803 individuals with 2 BP readings. Conclusion In patients with CKD, higher urinary sodium excretion is associated with higher BP, but unlike in general population, lower potassium excretion is not. Urinary Na/K does not add significant value in assessing high BP risk, except perhaps for hypertension control assessment., Graphical abstract

Published
2020
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4. MO484ADVERSE OUTCOMES ASSOCIATED WITH ORAL ANTITHROMBOTIC USE IN PATIENTS WITH MODERATE-TO-ADVANCED CHRONIC KIDNEY DISEASE*

Author

Sophie Liabeuf, Luc Frimat, Oriane Lambert, Marie Metzger, Solène M. Laville, Ziad A. Massy, Maurice Laville, Bénédicte Stengel, Denis Fouque, Carole Ayav, Christian Combe, Christian Jacquelinet, Roberto Pecoits-Filho, and Aghilès Hamroun

Subjects
Transplantation, medicine.medical_specialty, Nephrology, business.industry, Internal medicine, Antithrombotic, Medicine, In patient, business, medicine.disease, Kidney disease
Abstract

Background and Aims The use of oral antithrombotics in patients with chronic kidney disease (CKD) is challenging because of altered pharmacodynamics/pharmacokinetics. Patients prescribed oral anticoagulant are at high risk of bleeding, and possibly also acute kidney injury (AKI) and progression to kidney failure. We assessed bleeding, AKI, and kidney failure risks associated with oral anticoagulant and/or antiplatelet agent prescription in patients with moderate-to-advanced CKD. Method CKD-REIN is a prospective cohort of 3022 nephrology outpatients with CKD stages 2-5 at inclusion. Drug prescriptions and their duration were collected prospectively. We used cause-specific Cox proportional hazard models to estimate hazard ratios (HR) for bleeding (identified through hospitalizations), AKI (as defined according to KDIGO 2012), and kidney failure. Prescriptions of oral antithrombotics were treated as a time dependent variable and models were adjusted for baseline comorbidities, laboratory data, and other medications. Results At baseline, 339 (11%) patients (65% men; median age 69 [interquartile range (IQR), 60-76] years; median eGFR 32 [IQR, 23-41] were prescribed oral anticoagulants only, 1095 (36%) antiplatelet only, and 101 (3%) both anticoagulant and antiplatelet. Over a median follow-up of 3 years (IQR, 2.8-3.1), 152 patients experienced a bleeding event requiring hospital visit/stay (crude incidence rate (IR): 1.9% person-years [95%CI,1.6-2.2]), 414 patients experienced AKI (crude IR: 5.4 % person-years [4.9-5.9]), and 270 experienced kidney failure (crude IR: 3.4 % person-years [3.0-3.8]). A significant interaction was found between oral antithrombotics and eGFR (interaction p=0.03). The adjusted HRs [95%CI] for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants only, and antiplatelet + oral anticoagulant were respectively 0.58 [0.30; 1.11], 2.62 [1.39; 4.93], and 5.76 [2.85; 11.66] in patients with a baseline eGFR < 30 mL/min/1.73m2. In patients with baseline eGFR ≥ 30 mL/min/1.73m2, the adjusted HRs [95%CI] for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants .......only, and antiplatelet + oral anticoagulant were respectively 0.98 [0.48; 1.98], 1.91 [0.87; 4.20], and 1.54 [0.46; 5.12] (Figure 1A). An increased risk of AKI risk was associated with the prescription of oral anticoagulants (adjusted HR [95%CI]: 1.91[1.48; 2.46]) but not the prescription of antiplatelets (1.24[0.98; 1.56], Figure 1B). No significant interactions were found between oral anticoagulants and eGFR or antiplatelet agents. Kidney failure was not associated with the prescription of oral antithrombotics of any type (Figure 1C). No significant interactions were found with eGFR and antiplatelet agents. Conclusion This study confirms the risk of AKI in CKD patients prescribed oral anticoagulants. It also highlights the potential aggravating effect of combining anticoagulants and antiplatelet on the risk of bleeding in this population.

Published
2021
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5. Consequences of oral antithrombotic use in patients with chronic kidney disease

Author

Solène M. Laville, Christian Jacquelinet, Carole Ayav, Roberto Pecoits-Filho, Luc Frimat, Marie Metzger, Aghilès Hamroun, Denis Fouque, Bénédicte Stengel, Maurice Laville, Ziad A. Massy, Christian Combe, Sophie Liabeuf, Oriane Lambert, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Agence de la biomédecine [Saint-Denis la Plaine], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Association pour l'Utilisation du Rein Artificiel Région Lyonnaise (AURAL), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Néphrologie Transplantation, Dialyse et Aphérèse [CHU Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB), Arbor Research Collaborative for Health, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, ANR-10-COHO-0001,CKD-REIN,Maladie Rénale Chronique - Réseau Epidémiologie et Information en Néphrologie(2010), LAVILLE, Solène, Cohortes - Maladie Rénale Chronique - Réseau Epidémiologie et Information en Néphrologie - - CKD-REIN2010 - ANR-10-COHO-0001 - COHO - VALID, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chronic Kidney Disease - Réseau Epidémiologie et Information en Néphrologie (CKD REIN), and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Nephrology, Male, 030213 general clinical medicine, medicine.medical_specialty, Administration, Oral, RM1-950, 030226 pharmacology & pharmacy, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antithrombotic, Atrial Fibrillation, medicine, Humans, Prospective Studies, General Pharmacology, Toxicology and Pharmaceutics, Medical prescription, Renal Insufficiency, Chronic, Prospective cohort study, Aged, business.industry, General Neuroscience, Research, Hazard ratio, Acute kidney injury, Anticoagulants, General Medicine, Articles, Acute Kidney Injury, Middle Aged, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Disease Progression, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, Therapeutics. Pharmacology, Public aspects of medicine, RA1-1270, business, Adverse drug reaction, Platelet Aggregation Inhibitors, Kidney disease
Abstract

International audience; We assessed the risks of bleeding, acute kidney injury (AKI) and kidney failure associated with the prescription of antithrombotic agents (oral anticoagulants and/or antiplatelet agents) in patients with moderate-to-advanced CKD. CKD-REIN is a prospective cohort of 3022 nephrology outpatients with CKD stages 2-5 at baseline. We used cause-specific Cox proportional hazard models to estimate hazard ratios (HRs) for bleeding (identified through hospitalizations), AKI and kidney failure. Prescriptions of oral antithrombotics were treated as time-dependent variables. At baseline, 339 (11%) patients (65% men; 69 [60-76] years) were prescribed oral anticoagulants only, 1095 (36%) antiplatelets only, and 101 (3%) both type of oral antithrombotics. Over a median [IQR] follow-up period of 3.0[2.8-3.1] years, 152 patients experienced a bleeding event, 414 patients experienced an episode of AKI and 270 experienced kidney failure. The adjusted HRs [95%CI] for bleeding associated with prescriptions of antiplatelets only, oral anticoagulants only, and antiplatelet + oral anticoagulant were respectively 0.74[0.46; 1.19], 2.38[1.45; 3.89], and 3.96[2.20; 7.12]. An increased risk of AKI risk was associated with the prescription of oral anticoagulants (adjusted HR [95%CI]: 1.90[1.47; 2.45]) but not the prescription of antiplatelets (1.24[0.98; 1.56]). Kidney failure was not associated with the prescription of oral antithrombotics of any type. This study confirms the high risk of AKI associated with oral anticoagulants prescription in CKD patients and also highlights the potential aggravating effect of combining VKA and antiplatelets on the risk of bleeding.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Published
2021
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6. Higher mortality risk among kidney transplant recipients than among estimated glomerular filtration rate-matched patients with CKD-preliminary results

Author

Lynda Cheddani, Marie Metzger, Ziad A. Massy, Maryvonne Hourmant, Marie Essig, Tilman B. Drüeke, C. Kerleau, Christian Jacquelinet, Renaud Snanoudj, Sophie Liabeuf, Beverley Balkau, Nantes Kidney, Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Foch [Suresnes], Agence de la biomédecine [Saint-Denis la Plaine], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Ambroise Paré [AP-HP], Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Risk Factors, Internal medicine, Risk of mortality, Humans, Medicine, Prospective Studies, Renal Insufficiency, Chronic, education, Dialysis, Kidney transplantation, Aged, Transplantation, education.field_of_study, business.industry, Mortality rate, Hazard ratio, Middle Aged, Prognosis, medicine.disease, Kidney Transplantation, Transplant Recipients, Survival Rate, Cardiovascular Diseases, Nephrology, Case-Control Studies, Female, business, Glomerular Filtration Rate, Kidney disease
Abstract

BackgroundAlthough kidney transplantation prolongs survival relative to dialysis, it is associated with a higher death rate than in the general population. The objective of the present study was to assess and compare the risk of mortality and frequency of non-lethal cardiovascular (CV) events in kidney transplant recipients (KTRs) beyond 1 year after successful transplantation versus patients with chronic kidney disease (CKD) using propensity score–matched analysis of estimated glomerular filtration rate (eGFR) and other parameters.MethodsAfter propensity score matching, we studied 340 KTRs from the French Données Informatisées et Validées en Transplantation cohort and 605 non-transplant patients with CKD (CKDps) from the French Chronic Kidney Disease–Renal Epidemiology and Information Network cohort. The mean ± standard deviation eGFR was 42 ± 13 and 41 ± 12 mL/min/ 1.73 m2, respectively (P = 0.649). Descriptive data were completed by a survival analysis with Cox regression models.ResultsAfter a median follow-up period of 2.8 years (KTRs 2.0 years, CKDp 2.9 years), 71 deaths were recorded (31 and 40 in the KTR and CKD groups, respectively). Univariate analysis showed that KTRs had a significantly greater risk of mortality than CKDps. In multivariable analysis, KTRs were found to have a 2.7-fold greater risk of mortality [hazard ratio 2.7 (95% confidence interval 1.6–4.7); P = 0.005]. There was no between-group difference concerning the risk of CV events (P = 0.448). CV death rates in KTRs (29.0%) approximated those of CKDps (22.5%), whereas death rates due to infections were higher in KTRs (19.4% versus 10.0%).ConclusionBeyond 1 year after transplantation, KTRs, who possibly had a longer CKD history, had a significantly greater mortality risk than eGFR-matched CKDps. The excess risk was not associated with CV events.

Published
2021
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7. Conversion of Urine Protein-Creatinine Ratio or Urine Dipstick Protein to Urine Albumin-Creatinine Ratio for Use in Chronic Kidney Disease Screening and Prognosis: An Individual Participant-Based Meta-analysis

Author

Keiichi, Sumida, Girish N, Nadkarni, Morgan E, Grams, Yingying, Sang, Shoshana H, Ballew, Josef, Coresh, Kunihiro, Matsushita, Aditya, Surapaneni, Nigel, Brunskill, Steve J, Chadban, Alex R, Chang, Massimo, Cirillo, Kenn B, Daratha, Ron T, Gansevoort, Amit X, Garg, Licia, Iacoviello, Takamasa, Kayama, Tsuneo, Konta, Csaba P, Kovesdy, James, Lash, Brian J, Lee, Rupert W, Major, Marie, Metzger, Katsuyuki, Miura, David M J, Naimark, Robert G, Nelson, Simon, Sawhney, Nikita, Stempniewicz, Mila, Tang, Raymond R, Townsend, Jamie P, Traynor, José M, Valdivielso, Jack, Wetzels, Kevan R, Polkinghorne, Hiddo J L, Heerspink, Aditya, Surapeneni, Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Centre de recherche en épidémiologie et santé des populations (CESP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay

Subjects
Male, musculoskeletal diseases, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Urology, Renal function, Urine, Urinalysis, 01 natural sciences, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Diabetes mellitus, Internal Medicine, Medicine, Albuminuria, Humans, Mass Screening, 030212 general & internal medicine, 0101 mathematics, Stage (cooking), Renal Insufficiency, Chronic, skin and connective tissue diseases, Reagent Strips, Kidney, business.industry, 010102 general mathematics, General Medicine, Dipstick, Middle Aged, medicine.disease, Prognosis, 3. Good health, Proteinuria, medicine.anatomical_structure, Creatinine, Female, medicine.symptom, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, Kidney disease
Abstract

BACKGROUND: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead.OBJECTIVE: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging.DESIGN: Individual participant-based meta-analysis.SETTING: 12 research and 21 clinical cohorts.PARTICIPANTS: 919 383 adults with same-day measures of ACR and PCR or dipstick protein.MEASUREMENTS: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g).RESULTS: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR.LIMITATION: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample.CONCLUSION: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis.PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

Published
2020
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8. P0789SERUM URIC ACID IS ASSOCIATED WITH CHRONIC KIDNEY DISEASE PROGRESSION AND MORTALITY: INSIGHTS FROM THE CKD-REIN COHORT

Author

Christian Combe, Karen Leffondré, Jérôme Harambat, Bénédicte Stengel, Céline Lange, Marie Metzger, Oriane Lambert, Ziad A. Massy, and Mathilde Prezelin-Reydit

Subjects
Nephrology, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Urology, Renal function, 030204 cardiovascular system & hematology, urologic and male genital diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Medicine, Renal replacement therapy, Hyperuricemia, Prospective cohort study, Transplantation, Creatinine, business.industry, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, chemistry, Uric acid, business, Kidney disease
Abstract

Background and Aims The association between hyperuricemia and CKD progression is not well established in Europe and, to our knowledge, has not yet been investigated using longitudinal measurements. Method We used data from CKD-REIN, a prospective cohort study conducted in 40 representative French nephrology clinics, which included 3033 patients with CKD stages 3 to 5 between 2013 and 2016. Patients who had no serum uric acid or no creatinine measure at within 6 months of their inclusion date in the CKD-REIN study were excluded. All uric acid measures were taken into account, from inclusion to the occurrence of renal replacement therapy (RRT), death, or end of follow-up, whichever came first. We used a shared random-effect model for the joint analysis of individual trajectories of uric acid and the hazard of the composite outcome (RRT or death before RRT) and each specific event separately. Hazard ratio were adjusted (aHR) for age, sex, primary kidney disease, metabolic syndrome, cardiovascular disease, proteinuria (< 30, 30-300, > 300 mg/day), and the CKD-EPI estimated glomerular filtration rate (eGFR) at baseline. In a sensitivity analysis, we further adjusted for individual eGFR trajectory. Results A total of 2781 patients (65.5% men, median age 69 years) were included. At baseline, the median eGFR was 31.8 mL/min/1.73m2 and the median uric acid value was 425 µmol/L. During a median follow-up of 3.2 years, 434 patients received RRT and 264 died before RRT. At any time of follow-up, an increase of 100 µmol/l of the current value of uric acid was associated with a 16% increased hazard of RRT or death before RRT (aHR 1.16, 95% CI 1.07-1.26). The estimated effect of uric acid was similar with RRT (aHR 1.18, 95% CI 1.04-1.34) and death before RRT (aHR 1.16, 95% CI 1.05-1.28). When further adjusted for eGFR trajectory, the estimated effect of uric acid on the composite outcome was much weaker (aHR 1.06, 95% CI 0.98-1.16). Conclusion A higher current level of uric acid is associated with a strong increase in the hazard of RRT or death before RRT in European patients with CKD stage 3 to 5. However, the association is much weaker after adjustment for eGFR trajectory. Further analyses are necessary to better understand the dynamic of the association between uric acid and GFR.

Published
2020
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9. MO072LONGITUDINAL SERUM BICARBONATE MEASUREMENTS AND RISK OF CHRONIC KIDNEY DISEASE PROGRESSION AND MORTALITY: INSIGHTS FROM THE CKD-REIN COHORT

Author

Céline Lange, Mathilde Prezelin-Reydit, Karen Leffondré, Oriane Lambert, Marie Metzger, Christian Combe, Bénédicte Stengel, Jérôme Harambat, and Ziad A. Massy

Subjects
Nephrology, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, urologic and male genital diseases, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Renal replacement therapy, 10. No inequality, Prospective cohort study, Transplantation, Creatinine, Proteinuria, business.industry, Metabolic acidosis, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, chemistry, Cohort, medicine.symptom, business, Kidney disease
Abstract

Background and Aims Metabolic acidosis is a common complication of CKD and may contribute to CKD progression. However, the association between serum bicarbonate and CKD progression has not yet been investigated using longitudinal measurements. Method We used data from CKD-REIN, a prospective cohort study conducted in 40 representative French nephrology clinics which included 3033 patients with CKD stages 3 to 5 between 2013 and 2016. Patients who had no serum bicarbonate or no creatinine measure at within 6 months of their inclusion date in the CKD-REIN study were excluded. All serum bicarbonate measurements were taken into account, from inclusion to the occurrence of renal replacement therapy (RRT), death, or end of follow-up, whichever came first. We used a shared random-effect model for the joint analysis of individual trajectories of serum bicarbonate and the hazard of the composite outcome (RRT or death before RRT) and each specific event separately. Hazard ratio were adjusted (aHR) for age, sex, primary kidney disease, metabolic syndrome, cardiovascular disease, proteinuria (< 30, 30-300, > 300 mg/day), and the CKD-EPI estimated glomerular filtration rate (eGFR) at baseline. Results A total of 2977 patients (65.4% men, median age 69 years) were included. At baseline, the median eGFR was 31.8 mL/min/1.73m2 and the median bicarbonate concentration was 25 mmol/L. During a median follow-up of 4.5 years, 615 patients received RRT and 378 died before RRT. At any time of follow-up, a decrease of 1 mmol/l of the current level of serum bicarbonate was associated with a significantly increased hazard of RRT or death before RRT (aHR 1.05, 95%CI 1.02-1.08). The estimated effect was stronger on death before RRT (aHR 1.05, 95% CI 1.00-1.09) than on RRT (aHR 1.02, 95% CI 0.99-1.06). Conclusion A lower current level of serum bicarbonate is associated with an increased mortality in patients with CKD stage 3 to 5.

Published
2020
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10. Letter: how can we reduce mortality in elderly patients with acute severe ulcerative colitis? Authors' reply

Author

Catherine Dong, Marie Metzger, Einar E. Holsbø, Franck Carbonnel, Vittorio Perduca, Evolution, adaptation et comportement, Département écologie évolutive [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre de recherche en épidémiologie et santé des populations (CESP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay

Subjects
medicine.medical_specialty, Hepatology, business.industry, Gastroenterology, MEDLINE, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Ulcerative colitis, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, 030220 oncology & carcinogenesis, Internal medicine, medicine, Humans, Colitis, Ulcerative, 030211 gastroenterology & hepatology, Pharmacology (medical), Colitis, business, Immunosuppressive Agents, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Aged
Abstract

International audience

Published
2020
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11. Trajectory of extracellular fluid volume over time and subsequent risks of end-stage kidney disease and mortality in chronic kidney disease: a prospective cohort study

Author

Bénédicte Stengel, Pascal Houillier, A L Faucon, Karen Leffondré, Martin Flamant, C. Proust‐Lima, Jean-Jacques Boffa, Marie Metzger, Eric Thervet, François Vrtovsnik, Emmanuelle Vidal-Petiot, Jean-Philippe Haymann, Guillaume Geri, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux Population Health Research Center, Inserm, Bordeaux, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Ministère des Affaires Sociales et de la Santé: AOM 09114 R0 8156LL Institut National de la Santé et de la Recherche Médicale, Inserm Roche, and The NephroTest CKD cohort study is supported by the following grants: INSERM GIS-IReSP AO 8113LS TGIR, French Ministry of Health AOM 09114, INSERM AO 8022LS, Agence de la Biom?decine R0 8156LL, AURA and Roche 2009-152-447G.

Subjects
0301 basic medicine, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Volume overload, Urology, Renal function, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, extracellular fluid volume, Extracellular fluid, Internal Medicine, medicine, Humans, Prospective Studies, Prospective cohort study, sodium, business.industry, Hazard ratio, Confounding, volume overload, joint modelling, Extracellular Fluid, Middle Aged, medicine.disease, Prognosis, 3. Good health, 030104 developmental biology, trajectory, Cohort, Disease Progression, Kidney Failure, Chronic, Female, business, chronic kidney disease, Kidney disease, Glomerular Filtration Rate
Abstract

International audience; Background: Extracellular fluid volume (ECF) is independently associated with chronic kidney disease (CKD) progression and mortality in patients with CKD, but the prognostic value of the trajectory of ECF over time beyond that of baseline value is unknown. Objectives: To characterize ECF trajectory and evaluate its association with the risks of end-stage kidney disease (ESKD) and mortality. Methods: From the prospective tricentric NephroTest cohort, we included 1588 patients with baseline measured glomerular filtration rate (mGFR) ≥15 mL min−1/1.73 m2 and ECF measurement. ECF and GFR were measured repeatedly using the distribution volume and clearance of 51Cr-EDTA, respectively. ESKD and mortality were traced through record linkage with the national registries. Adjusted shared random-effect joint models were used to analyse the association between the trajectory of ECF over time and the two competing outcomes. Results: Patients were mean age 58.7 years, 66.7% men, mean mGFR of 43.6 ± 18.6 mL min−1/1.73 m2 and mean ECF of 16.1 ± 3.6 L. Over a median follow-up of 5.3 [IQR: 3.0;7.4] years, ECF increased by 136 [95%CI 106;167] mL per year on average, whilst diuretic prescription and 24-hour urinary sodium excretion remained stable. ESKD occurred in 324 (20.4%) patients, and 185 (11.6%) patients died before ESKD. A higher current value of ECF was associated with increased hazards of ESKD (adjusted hazard ratio [aHR]: 1.12 [95%CI 1.06;1.18]; P

Published
2020
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12. Impact of age on cardiovascular drug use in patients with chronic kidney disease

Author

Sophie Liabeuf, Marie Metzger, Christian Jacquelinet, Denis Fouque, Ronald L. Pisoni, Luc Frimat, Ziad A. Massy, Cédric Villain, Nicolas Mansencal, Maurice Laville, Serge Briançon, Christian Combe, Bénédicte Stengel, Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], CHU Amiens-Picardie, Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Agence de la biomédecine [Saint-Denis la Plaine], Service de Néphrologie [Lyon], Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Arbor Research Collaborative for Health, Service de cardiologie et maladies vasculaires [CHU Ambroise Paré], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Vialaron, Sylvie

Subjects
medicine.medical_specialty, underuse, 030204 cardiovascular system & hematology, elderly, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antithrombotic, Medicine, atrial fibrillation, Stroke, Transplantation, business.industry, Atrial fibrillation, Odds ratio, Original Articles, medicine.disease, stroke, 3. Good health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Nephrology, Cardiovascular agent, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, 030217 neurology & neurosurgery, Fibrinolytic agent, chronic kidney disease, coronary artery disease, Kidney disease
Abstract

Background Elderly patients with chronic kidney disease (CKD) are often excluded from clinical trials; this may affect their use of essential drugs for cardiovascular complications. We sought to assess the impact of age on cardiovascular drug use in elderly patients with CKD. Methods We used baseline data from the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort including 3033 adult patients with CKD Stages 3 and 4. We studied the use of recommended drugs for coronary artery disease (CAD), stroke and atrial fibrillation by age, after adjusting for socio-demographic and clinical conditions. Results The patients’ mean age was 66.8 years (mean estimated glomerular filtration rate 32.9 mL/min/1.73 m2). The prevalence of CAD was 24.5% [81.3% receiving antiplatelet agents, 75.6% renin–angiotensin system (RAS) blockers, 65.4% β-blockers and 81.3% lipid-lowering therapy], that of stroke 10.0% (88.8% receiving antithrombotic drugs) and that of atrial fibrillation 11.1% (69.5% receiving oral anticoagulants). Compared with patients aged Conclusions In patients with CKD, older age per se was not associated with the underuse of antithrombotic drugs but was for other major drugs, with a potential impact on cardiovascular outcomes.

Published
2020
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13. Adverse Drug Reactions in Patients with CKD

Author

Valérie Gras-Champel, Luc Frimat, Solène M. Laville, Marie Metzger, Ziad A. Massy, Maurice Laville, Christian Combe, Christian Jacquelinet, Julien Moragny, Sophie Liabeuf, Bruce M. Robinson, Bénédicte Stengel, Denis Fouque, Épidémiologie des radiations, épidémiologie clinique des cancers et survie (U1018 (Équipe 3) ), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Hôpital Paul Brousse, CHU Amiens-Picardie, Service de dermatologie [CHU d'Amiens-Picardie], Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche en Nutrition Humaine Rhône - Alpes, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de néphrologie-hémodialyse-transplantation [CHRU Nancy], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Mécanismes physiologiques et conséquences des calcifications cardiovasculaires: rôle des remodelages cardiovasculaires et osseux, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Agence de la biomédecine [Saint-Denis la Plaine], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Arbor Research Collaborative for Health, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, LAVILLE, Solène, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay-Hôpital Paul Brousse, INSERM U1026 (INSERM, U1026), Institut National de la Santé et de la Recherche Médicale (INSERM), Association pour l'Utilisation du Rein Artificiel Région Lyonnaise (AURAL), Centre Hospitalier Universitaire Ambroise Paré (CHU Ambroise Paré), and Université de Picardie Jules Verne (UPJV)

Subjects
medicine.medical_specialty, pharmacoepidemiology, Drug-Related Side Effects and Adverse Reactions, Epidemiology, [SDV]Life Sciences [q-bio], adverse drug reaction, 030232 urology & nephrology, Critical Care and Intensive Care Medicine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Medical Records, Cohort Studies, Renin-Angiotensin System, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Humans, Medicine, risk factors, 030212 general & internal medicine, Renal Insufficiency, Renal Insufficiency, Chronic, Chronic, Transplantation, glomerular filtration rate, adverse drug reactions, business.industry, Incidence (epidemiology), renin-angiotensin system inhibitors, Original Articles, Pharmacoepidemiology, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, antithrombotic agents, diuretics, 3. Good health, Clinical trial, Pharmaceutical Preparations, Nephrology, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cohort, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Adverse drug reaction, chronic kidney disease, Cohort study, hospitalization
Abstract

International audience; BACKGROUND AND OBJECTIVES: Little is known about the burden of adverse drug reactions in CKD. We estimated the incidence of overall and serious adverse drug reactions and assessed the probability of causation, preventability, and factors associated with adverse drug reactions in patients seen by nephrologists. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Chronic Kidney Disease-Renal Epidemiology and Information Network cohort included 3033 outpatients (65% men) with CKD and eGFR\textless60 ml/min per 1.73 m(2), with follow-up for 2 years. Adverse drug reactions were identified from hospitalization reports, medical records, and participant interviews and finally assessed for causality, preventability, and immediate therapeutic management by experts in pharmacology. RESULTS: Median (interquartile range) age was 69 (60-76) years old; 55% had eGFR≥30 ml/min per 1.73 m(2), and 45% had eGFR\textless30 ml/min per 1.73 m(2). Participants were prescribed a median (range) of eight (five to ten) drugs. Over 2 years, 536 patients had 751 adverse drug reactions, 150 (in 125 participants) classified as serious, for rates of 14.4 (95% confidence interval, 12.6 to 16.5) and 2.7 (95% confidence interval, 1.7 to 4.3) per 100 person-years, respectively. Among the serious adverse drug reactions, 32% were considered preventable or potentially preventable; 16 caused death, directly or indirectly. Renin-angiotensin system inhibitors (15%), antithrombotic agents (14%), and diuretics (10%) were the drugs to which the most adverse drug reactions were imputed, but antithrombotic agents caused 34% of serious adverse drug reactions. The drug was discontinued in 71% of cases, at least temporarily. Adjusted hazard ratios for serious adverse drug reaction were significantly higher in patients with eGFR\textless30 versus ≥30 ml/min per 1.73 m(2) (1.8; 95% confidence interval, 1.3 to 2.6), in those prescribed more than ten versus less than five medications (2.4; 95% confidence interval, 1.1 to 5.2), or in those with poor versus good adherence (1.6; 95% confidence interval, 1.4 to 2.4). CONCLUSIONS: Adverse drug reactions are common and sometimes serious in patients with CKD. Many serious adverse drug reactions may be preventable. Some specific pharmacologic classes, particularly antithrombotic agents, are at risk of serious adverse drug reactions. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN), NCT03381950.

Published
2020
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14. Adverse outcomes of proton pump inhibitors in patients with chronic kidney disease: The CKD-REIN cohort study

Author

Sophie Liabeuf, Solène M Laville, Roberto Pecoits-Filho, Marie Metzger, Chronic Kidney Disease-Renal Epidemiology, Ziad A. Massy, Luc Frimat, Denis Fouque, Bénédicte Stengel, Maurice Laville, Oriane Lambert, Christian Jacquelinet, Aghilès Hamroun, CHU Amiens-Picardie, Université de Picardie Jules Verne (UPJV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Adaptation, mesure et évaluation en santé. Approches interdisciplinaires (APEMAC), Université de Lorraine (UL), Arbor Research Collaborative for Health, Université de Lyon, Agence de la biomédecine [Saint-Denis la Plaine], Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Chronic Kidney Disease - Réseau Epidémiologie et Information en Néphrologie (CKD REIN), Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and CarMeN, laboratoire

Subjects
Male, Nephrology, medicine.medical_specialty, pharmacoepidemiology, renal risk, [SDV]Life Sciences [q-bio], Population, 030226 pharmacology & pharmacy, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Interquartile range, Internal medicine, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Renal Insufficiency, Chronic, education, Pharmacology, education.field_of_study, business.industry, Hazard ratio, Acute kidney injury, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], acute kidney injury, Cohort, Kidney Failure, Chronic, Female, proton pump inhibitors, business, chronic kidney disease, Glomerular Filtration Rate, Cohort study, Kidney disease
Abstract

International audience; AIMS: Long-term use of proton pump inhibitors (PPIs) has been associated with adverse kidney events in the general population, but their impact among chronic kidney disease (CKD) patients is unclear. We studied the prevalence and incidence (new users) of PPI prescriptions and their relation to kidney outcomes and mortality in CKD patients. METHODS: We collected drug prescriptions prospectively in a cohort of 3023 nephrology outpatients with CKD stages 2-5 at inclusion. Hazard ratios (HR, 95% confidence intervals [95% CI]) for acute kidney injury (AKI), end-stage kidney disease (ESKD), and mortality associated with new PPI prescriptions as a time-dependent variable were estimated with cause-specific Cox models in 1940 non-users with eGFR ≥ 15 mL/min/1.73 m(2) at baseline, adjusted for comorbidities, laboratory data and drugs. RESULTS: There were 981/3023 (32%) prevalent users (67 ± 13 years, 65% men) at baseline, and 366/3023 (12%) were prescribed PPI (new users) over a median follow-up of 3.9 years (interquartile range, 3-4.2). Among these new users, their median cumulative duration of prescription was 1 year (interquartile range: 0.4-2.3). During follow-up, 354 patients developed ESKD and 216 died before ESKD. The adjusted HRs associated with PPI prescription were 1.74 (95% CI, 1.26-2.40) for ESKD and 2.42 (95% CI, 1.73-3.39) for all-cause mortality. Over the first 3 years of follow-up, 211 AKI events had occurred. The adjusted HR for AKI associated with PPI prescription was 2.89 (95% CI, 1.91-4.38). CONCLUSIONS: Long-term PPI prescription was common in CKD patients. Our results call attention to its potential risks of both acute and chronic kidney failure.

Published
2020
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15. A Predictive Model for Progression of CKD to Kidney Failure Based on Routine Laboratory Tests

Author

Philip A. Kalra, Peter J. Oefner, Anna Köttgen, Sahar Ghasemi, Peggy Sekula, Helena U. Zacharias, Ulla T. Schultheiss, Ibrahim Ali, Bénédicte Stengel, Kai-Uwe Eckardt, Johannes Raffler, Michael Altenbuchinger, Marie Metzger, Wolfram Gronwald, Florian Kronenberg, Matthias Schmid, Ziad A. Massy, Christian Combe, Fruzsina Kotsis, Inga Steinbrenner, Barbara Kollerits, Bioingénierie tissulaire (BIOTIS), and Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
German Chronic Kidney Disease Study, Chronic Kidney Disease, Kidney Failure Requiring Kidney Replacement Therapy, Machine Learning, Risk Equation, medicine.medical_specialty, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, end-stage kidney disease (ESKD), kidney failure risk equation, CKD progression, Concordance, 030232 urology & nephrology, Chronic kidney disease (CKD), kidney disease trajectory, kidney failure requiring kidney replacement therapy (KFRT), German Chronic Kidney Disease study, risk equation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Renal Insufficiency, 030212 general & internal medicine, Renal Insufficiency, Chronic, Creatinine, Framingham Risk Score, Proportional hazards model, business.industry, medicine.disease, machine learning, chemistry, Nephrology, Cohort, Disease Progression, Kidney Failure, Chronic, Observational study, business, Glomerular Filtration Rate, Cohort study, Kidney disease
Abstract

RATIONALE & OBJECTIVE: Stratification of chronic kidney disease (CKD) patients at risk for progressing to end-stage kidney disease (ESKD) requiring kidney replacement therapy (KRT) is important for clinical decision-making and trial enrollment. STUDY DESIGN: Four independent prospective observational cohort studies. SETTING & PARTICIPANTS: The development cohort was comprised of 4,915 CKD patients and three independent validation cohorts were comprised of a total of 3,063. Patients were followed-up for approximately five years. NEW PREDICTORS & ESTABLISHED PREDICTORS: 22 demographic, anthropometric and laboratory variables commonly assessed in CKD patients. OUTCOMES: Progression to ESKD requiring KRT. ANALYTICAL APPROACH: A Least Absolute Shrinkage and Selection Operator (LASSO) Cox proportional hazards model was fit to select laboratory variables that best identified patients at high risk for ESKD. Model discrimination and calibration were assessed and compared against the 4-variable Tangri (T4) risk equation. Both used a resampling approach within the development cohort and in the validation cohorts using cause-specific concordance (C) statistics, net reclassification improvement, and calibration graphs. RESULTS: The newly derived 6-variable (Z6) risk score included serum creatinine, albumin, cystatin C and urea, as well as hemoglobin and the urine albumin-to-creatinine ratio. Based on the resampling approach, Z6 achieved a median C value of 0.909 (95% CI, 0.868-0.937) at two years after the baseline visit, whereas the T4 achieved a median C value of 0.855 (95% CI, 0.799-0.915). In the three independent validation cohorts, Z6 C values were 0.894, 0.921, and 0.891, whereas the T4 C values were 0.882, 0.913, and 0.862. LIMITATIONS: The Z6 was both derived and tested only in White European cohorts. CONCLUSIONS: A new risk equation, based on six routinely available laboratory tests facilitates identification of patients with CKD who are at high risk of progressing to ESKD.

Published
2022
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16. Potential Surrogate Outcomes for Kidney Failure in Advanced CKD: Evaluation of Power and Predictive Ability in CKDopps

Author

Jarcy Zee, Daniel Muenz, Keith P. McCullough, Brian Bieber, Marie Metzger, Natalia Alencar de Pinho, Antonio A. Lopes, Danilo Fliser, Bruce M. Robinson, Eric Young, Ronald L. Pisoni, Bénédicte Stengel, Roberto Pecoits-Filho, Christian Combe, Johannes Duttlinger, Christian Jacquelinet, Gerhard Lonnemann, Antonio Lopes, Ziad Massy, Helmut Reichel, Takashi Wada, and Kunihiro Yamagata

Subjects
Nephrology, Internal Medicine
Abstract

Potential surrogate end points for kidney failure have been proposed in chronic kidney disease (CKD); however, they must be evaluated to ensure accurate, powerful, and harmonized research, particularly among patients with advanced CKD. The aim of the current study was to investigate the power and predictive ability of surrogate kidney failure end points in a population with moderate-to-advanced CKD.Analysis of longitudinal data of a large multinational CKD observational study (Chronic Kidney Disease Outcomes and Practice Patterns Study).CKD stage 3-5 patients from Brazil, France, Germany, and the United States.Reaching an estimated glomerular filtration rate (eGFR) 15 mL/min/1.73 mEach end point was used as a time-varying indicator in the Cox model to predict the time to kidney replacement therapy (KRT; dialysis or transplant) and was compared by the number of events and prediction accuracy.8,211 patients had a median baseline eGFR of 27 mL/min/1.73 mVariable visit frequency resulted in variable eGFR measurement frequency.The composite end point can be useful for CKD progression studies among patients with advanced CKD. Harmonized use of this approach has the potential to accelerate the translation of new discoveries to clinical practice by identifying risk factors and treatments for kidney failure.

Published
2022
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17. Evaluation of the adequacy of drug prescriptions in patients with chronic kidney disease: results from the CKD-REIN cohort

Author

Solène M. Laville, Bénédicte Stengel, Bruce M. Robinson, Denis Fouque, Marie Metzger, Ziad A. Massy, Luc Frimat, Christian Combe, Maurice Laville, Carole Ayav, Sophie Liabeuf, Elodie Speyer, and Christian Jacquelinet

Subjects
Pharmacology, medicine.medical_specialty, business.industry, 030232 urology & nephrology, Renal function, Odds ratio, urologic and male genital diseases, Inappropriate Prescriptions, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Cohort, Cardiovascular agent, Medicine, Pharmacology (medical), 030212 general & internal medicine, Medical prescription, business, Kidney disease
Abstract

Aims Drug prescription is difficult to manage in patients with chronic kidney disease (CKD). We assessed the prevalence and determinants of inappropriate drug prescriptions (whether contraindications or inappropriately high doses) with regard to kidney function in patients with CKD under nephrology care. We also assessed the impact of the equation used to estimate GFR on the prevalence estimates. Methods Results The CKD-REIN cohort includes 3033 outpatients with CKD (eGFR between 15 and 60 ml min(-1) 1.73 m(-2)). We examined the daily doses of pharmacological agents prescribed at study entry. Inappropriate prescription was defined as the reported prescription of either a contraindicated drug or an indicated drug at an inappropriately high dose level with regard to the patient's GFR, as estimated with the CKD-EPI equation, the de-indexed CKD-EPI equation, or the Cockcroft-Gault (CG) equation. Multivariate logistic regression was used to assess the determinants of inappropriate prescription risk. At baseline, patients' median [interquartile range] number of drugs prescribed per patient was 8 [5-10]. Half of the patients had been prescribed at least one inappropriate drug. Anti-gout, cardiovascular agents and antidiabetic agents accounted for most of the inappropriate prescriptions. The percentage of inappropriate prescriptions varied from one GFR equation to another: 52% when using the CKD-EPI equation, 47% when using the de-indexed CKD-EPI equation and 41% with the CG equation. A multiple logistic regression analysis showed significantly higher odds ratios [95% confidence interval] for inappropriate prescriptions in male patients (1.28 [1.07; 1.53]), patients with diabetes (1.34 [1.06; 1.70]), those with a high BMI (1.58 [1.25; 1.99]), and those with a low GFR (10.2 [6.02; 17.3]). The risk of having at least one inappropriate prescription increased with the number of drugs per patient (P for trend \textless 0.0001) and therefore the odds ratio was 5.88 [4.17; 8.28] for those who received at least 11 prescribed medications compared to those who received fewer than 5. Conclusion Appendix Our results emphasize the complexity of drug management for CKD patients, for whom inappropriate prescription appears to be common.

Published
2018
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18. Hypertension Control, Apparent Treatment Resistance, and Outcomes in the Elderly Population With Chronic Kidney Disease

Author

Tilman B. Drüeke, Claudine Berr, Bénédicte Stengel, Marie Metzger, Ziad A. Massy, Jean Kaboré, Christophe Tzourio, and Catherine Helmer

Subjects
medicine.medical_specialty, hypertension, Renal function, 030204 cardiovascular system & hematology, lcsh:RC870-923, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Internal medicine, Elderly population, medicine, 030212 general & internal medicine, Treatment resistance, Intensive care medicine, Stroke, Cardiovascular mortality, Hypertension control, business.industry, cardiovascular, Hazard ratio, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, female genital diseases and pregnancy complications, Nephrology, business, chronic kidney disease, Kidney disease
Abstract

Introduction Chronic kidney disease (CKD) is often associated with poor hypertension control and treatment resistance, but whether CKD modifies the effect of hypertension control on outcomes is unknown. Methods We studied 10-year mortality and cardiovascular events according to hypertension control status and CKD (glomerular filtration rate

Published
2017
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19. International variation in the management of mineral bone disorder in patients with chronic kidney disease: Results from CKDopps

Author

Jarcy Zee, Bénédicte Stengel, Friedrich K. Port, Keith McCullough, Sophie Liabeuf, Ziad A. Massy, Philipp A. Csomor, Roberto Pecoits-Filho, Marie Metzger, Ronald L. Pisoni, Helmut Reichel, Bruce G. Robinson, Eric W. Young, CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre de recherche en épidémiologie et santé des populations (CESP), and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Histology, Internationality, Bone disease, Physiology, medicine.drug_class, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Gastroenterology, vitamin D deficiency, Nephrologists, 03 medical and health sciences, Hyperphosphatemia, 0302 clinical medicine, Internal medicine, Surveys and Questionnaires, medicine, Vitamin D and neurology, Humans, Practice Patterns, Physicians', Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Aged, Probability, Chronic Kidney Disease-Mineral and Bone Disorder, Hyperparathyroidism, business.industry, Middle Aged, medicine.disease, 3. Good health, Phosphate binder, 030104 developmental biology, Female, business, Biomarkers, Kidney disease, Glomerular Filtration Rate
Abstract

Background and objectives Chronic kidney disease (CKD) is commonly associated with mineral and bone metabolism disorders, but these are less frequently studied in non-dialysis CKD patients than in dialysis patients. We examined and described international variation in mineral and bone disease (MBD) markers and their treatment and target levels in Stage 3–5 CKD patients. Design, setting, participants, and measurements Prospective cohort study of 7658 adult patients with eGFR Results Over two-thirds of the patients had MBD markers measured at time intervals in line with practice guidelines. P and iPTH increased and Ca decreased gradually from eGFR 60–20 mL/min/1.73m2 and more sharply for eGFR 5.5 mg/dL, phosphate binder use was 14% to 43% across the four countries. Among patients with PTH >300 pg/mL, use of active (calcitriol and related analogs) vitamin D was 12%–51%, and use of any (active or nutritional) vitamin D was 60%–87%. Conclusions Although monitoring of CKD-MBD laboratory markers by nephrologists in CKDopps countries is consistent with guidelines, target levels vary notably and prescription of medications to treat abnormalities in these laboratory markers is generally low in these cross-sectional analyses. While there are opportunities to increase treatment of hyperphosphatemia, hyperparathyroidism, and vitamin D deficiency in advanced CKD, the effect on longer-term complications of these conditions requires study.

Published
2019
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20. Prescription patterns of dialysate potassium and potassium binders and survival on haemodialysis-the French Renal Epidemiology and Information Network registry

Author

Bénédicte Stengel, Stéphane Edet, Marie Metzger, Oriane Lambert, Christian Jacquelinet, Lucile Mercadal, Sylvie Merle, and Cécile Couchoud

Subjects
Male, medicine.medical_specialty, Potassium, medicine.medical_treatment, chemistry.chemical_element, Gastroenterology, chemistry.chemical_compound, Renal Dialysis, Internal medicine, Dialysis Solutions, Epidemiology, medicine, Potassium binder, Humans, Registries, Medical prescription, AcademicSubjects/MED00340, Survival analysis, Aged, Transplantation, business.industry, Hazard ratio, Editorials, Middle Aged, Prognosis, Confidence interval, Survival Rate, Prescriptions, chemistry, Nephrology, Kidney Failure, Chronic, Female, Hemodialysis, business
Abstract

Background Management of potassium disorders in patients on haemodialysis (HD) is complex. We studied prescription patterns of dialysate potassium and potassium binders, and their associations with patient survival. Methods This national registry-based study included 25 629 incident adult patients alive after 3 months of HD from 2010 through 2013 and followed-up through 31 December 2014. We used Cox proportional hazard models to estimate multiadjusted mortality hazard ratios (HRs) associated with time-dependent exposure to facility-level dialysate potassium concentrations and patient-level potassium binder exposure. Results Almost all dialysis units used, and generally most often, dialysate potassium concentrations of 2 mmol/L. During this period, use of concentrations Conclusions Diversity in facility-level use of dialysate potassium concentrations and potassium binder use at an appropriate dose appear to be associated with better survival in HD patients.

Published
2019

21. Achievement of Low-Density Lipoprotein Cholesterol Targets in CKD

Author

Ziad A. Massy, Jean Ferrières, Eric Bruckert, Céline Lange, Sophie Liabeuf, Maja Velkovski-Rouyer, Bénédicte Stengel, Carole Ayav, Christian Combe, Denis Fouque, Luc Frimat, Yves-Edouard Herpe, Maurice Laville, Ziad Massy, Karine Legrand, Marie Metzger, Elodie Speyer, Bruno Moulin, Gaétan Lebrun, Éric Magnant, Gabriel Choukroun, Jean Philippe Bourdenx, Marie Essig, Raymond Azar, Mustafa Smati, Mohamed Jamali, Alexandre Klein, Michel Delahousse, Séverine Martin, Eric Thervet, Xavier Belenfant, Pablo Urena, Carlos Vela, Dominique Chauveau, Viktor Panescu, François Glowacki, Maxime Hoffmann, Maryvonne Hourmant, Dominique Besnier, Angelo Testa, Philippe Zaoui, Charles Chazot, Laurent Juillard, Stéphane Burtey, Adrien Keller, Nassim Kamar, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], Service d'Endocrinologie, Métabolisme et Prévention des Maladies Cardio-vasculaires [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut E3M [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence de la biomédecine [Saint-Denis la Plaine], CHU Amiens-Picardie, Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service d’Endocrinologie, Métabolisme et Prévention des Risques Cardio-Vasculaires [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Nephrology, medicine.medical_specialty, Statin, medicine.drug_class, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 030204 cardiovascular system & hematology, lcsh:RC870-923, lipids, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Ezetimibe, Clinical Research, cardiovascular disease, Diabetes mellitus, Internal medicine, medicine, Prospective cohort study, Kidney transplantation, low-density lipoprotein cholesterol, lipid-regulating agents, business.industry, Cholesterol, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, chronic kidney diseases, 3. Good health, chemistry, business, medicine.drug, Kidney disease
Abstract

Introduction: We describe the characteristics of patients with moderate/advanced chronic kidney disease (CKD) according to receipt of lipid-lowering therapy (LLT), and whether they achieved low-density lipoprotein cholesterol (LDL-C) targets for high- and very high-risk patients. Methods: CKD-REIN (NCT03381950), a prospective cohort study conducted in 40 nephrology clinics in France, enrolled 3033 patients with moderate (stage G3) or advanced (stage G4/G5) CKD (2013−2016) who had not been on chronic dialysis or undergone kidney transplantation. Data were collected from patients’ interviews and medical records. Patients were followed up at 1 year. Results: Among 2542 patients (mean [SD] age 67 [13] years, 34% women) with LDL-C measurements at baseline (mean [SD] LDL-C 2.7 [1.1] mmol/l; cholesterol 4.8 [1.3] mmol/l), 63% were on LLT; 24% were at high (CKD stage G3, no cardiovascular disease [CVD] or diabetes) and 74% at very high (CKD stage G3 with diabetes or CVD, or CKD stage G4/5) cardiovascular risk. Among high-risk patients, 45% of those on statin and/or ezetimibe achieved the LDL-C treatment target (

Published
2019
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22. FP376INCIDENCE AND DETERMINANTS OF ADVERSE DRUG REACTIONS IN PATIENTS WITH CKD FROM THE CKD-REIN COHORT STUDY

Author

Marie Metzger, Bénédicte Stengel, Ziad A. Massy, Maurice Laville, Christian Jacquelinet, Solène M. Laville, Julien Moragny, Ronald L. Pisoni, Luc Frimat, Christian Combe, Denis Fouque, Valérie Gras, and Sophie Liabeuf

Subjects
Transplantation, medicine.medical_specialty, Nephrology, business.industry, Internal medicine, medicine, In patient, Drug reaction, business, Cohort study
Published
2019
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23. Impact of sex and glucose-lowering treatments on hypoglycaemic symptoms in people with type 2 diabetes and chronic kidney disease. The French Chronic Kidney Disease – Renal Epidemiology and Information Network (CKD-REIN) Study

Author

L. Frimat, Christian Jacquelinet, Serge Briançon, Denis Fouque, Elodie Speyer, Fabrizio Andreelli, R. Pisoni, Carole Ayav, Ziad A. Massy, Bénédicte Stengel, Maurice Laville, Beverley Balkau, Marie Metzger, Christian Combe, University of Versailles St.-Quentin, UMRS 1018, Villejuif, Service de Diabétologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Arbor Research Collaborative for Health, CKD REIN, Service de diabétologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and CCSD, Accord Elsevier

Subjects
Male, medicine.medical_specialty, Databases, Factual, Epidemiology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Renal function, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, Chronic kidney disease, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Diabetic Nephropathies, Renal Insufficiency, Chronic, ComputingMilieux_MISCELLANEOUS, Aged, Information Services, business.industry, Insulin, General Medicine, medicine.disease, 3. Good health, Metformin, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Albuminuria, Drug Therapy, Combination, Female, Sex, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, medicine.symptom, Glucose lowering treatments, business, Hypoglycaemia, medicine.drug, Kidney disease
Abstract

Aim To describe current practices of glucose-lowering treatments in people with diabetes and chronic kidney disease (CKD), the associated glucose control and hypoglycaemic symptoms, with an emphasis on sex differences. Methods Among the 3033 patients with CKD stages 3–5 recruited into the French CKD-REIN study, 645 men and 288 women had type 2 diabetes and were treated by glucose-lowering drugs. Results Overall, 31% were treated only with insulin, 28% with combinations of insulin and another drug, 42% with non-insulin glucose-lowering drugs. In CKD stage 3, 40% of patients used metformin, 12% at stages 4&5, similar for men and women; in CKD stage 3, 53% used insulin, similar for men and women, but at stages 4&5, 59% of men and 77% of women used insulin. Patients were reasonably well controlled, with a median HbA1c of 7.1% (54 mmol/mol) in men, 7.4% (57 mmol/mol) in women (P = 0.0003). Hypoglycaemic symptoms were reported by 40% of men and 59% of women; they were not associated with the estimated glomerular filtration rate, nor with albuminuria or with HbA1c in multivariable analyses, but they were more frequent in people treated with insulin, particularly with fast-acting and pre-mixed insulins. Conclusion Glucose-lowering treatment, HbA1c and hypoglycaemic symptoms were sex dependent. Metformin use was similar in men and women, but unexpectedly low in CKD stage 3; its use could be encouraged rather than resorting to insulin. Hypoglycaemic symptoms were frequent and need to be more closely monitored, with appropriate patient-education, especially in women.

Published
2019
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24. Predicting kidney failure from longitudinal kidney function trajectory: A comparison of models

Author

Ron T. Gansevoort, Bénédicte Stengel, Marie Metzger, Hiddo J.L. Heerspink, Jack F.M. Wetzels, Jan A.J.G. van den Brand, Peter J. Blankestijn, Tjeerd M. H. Dijkstra, Department of nephrology [Nimègue, Pays-Bas], Radboud Institute for Health Sciences [Nimègue, Pays-Bas], Radboud University Medical Center [Nijmegen]-Radboud University Medical Center [Nijmegen], Max Planck Institute for Developmental Biology, Max-Planck-Gesellschaft, Center for Integrative Neuroscience [Tubingue, Allemagne], University of Tübingen, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Department of Nephrology [Utrecht, Pays-Bas], University Medical Center [Utrecht], Department of Clinical Pharmacy and Pharmacology [Groningue, Pays-Bas], University Medical Center Groningen [Groningen] (UMCG), Department of Nephrology [Groningue, Pays-Bas], JAJGvdB is supported by grant DKF14OKG07 from the Dutch Kidney Foundation (www.nierstichting.nl), TD was supported by CogIMon H2020 ICT-644727. (https://ec.europa.eu/programmes/horizon2020/en/). The MASTERPLAN Study was supported by grant number PV01 from the Dutch Kidney Foundation (www.nierstichting.nl) and grant 2003B261 from the Netherlands Heart Foundation (Nederlandse Hartstichting, (www.hartstichting.nl). In addition, unrestricted grants were provided by Amgen, Genzyme, Pfizer and Sanofi-Aventis for the MASTERPLAN study. The NephroTest cohort study was supported by the following grants: INSERM (www.inserm.fr) GIS-IReSP AO 8113LS TGIR (B.S.), French Ministry of Health AOM 09114 (M.Fr.), INSERM AO 8022LS (B.S.), Agence de la Biomédecine R0 8156LL (B.S.), AURA (M.Fr.) and Roche 2009-152-447G (M.Fr.)., Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Bodescot, Myriam, Groningen Kidney Center (GKC), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Cardiovascular Centre (CVC)

Subjects
Oncology, Male, Physiology, 030232 urology & nephrology, Blood Pressure, Kidney Function Tests, Vascular Medicine, Biochemistry, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Mathematical and Statistical Techniques, Skeletal Joints, Chronic Kidney Disease, Medicine and Health Sciences, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Musculoskeletal System, Multidisciplinary, Agricultural and Biological Sciences(all), Statistics, Middle Aged, Prognosis, Nephrology, Creatinine, Cohort, Physical Sciences, Disease Progression, Medicine, Female, medicine.symptom, Anatomy, Research Article, Glomerular Filtration Rate, medicine.medical_specialty, Science, Renal function, Research and Analysis Methods, Risk Assessment, 03 medical and health sciences, Diagnostic Medicine, Internal medicine, medicine, Journal Article, Humans, Statistical Methods, Renal Insufficiency, Chronic, General, Survival analysis, Renal Physiology, Models, Statistical, Proportional hazards model, business.industry, Biochemistry, Genetics and Molecular Biology(all), Data Science, Repeated measures design, Biology and Life Sciences, Kidneys, Renal System, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Albuminuria, Kidney Failure, Chronic, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, Biomarkers, Mathematics, Kidney disease, Forecasting, Genetics and Molecular Biology(all)
Abstract

Contains fulltext : 205516.pdf (Publisher’s version ) (Open Access) RATIONALE & OBJECTIVE: Early prediction of chronic kidney disease (CKD) progression to end-stage kidney disease (ESKD) currently use Cox models including baseline estimated glomerular filtration rate (eGFR) only. Alternative approaches include a Cox model that includes eGFR slope determined over a baseline period of time, a Cox model with time varying GFR, or a joint modeling approach. We studied if these more complex approaches may further improve ESKD prediction. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: We re-used data from two CKD cohorts including patients with baseline eGFR >30ml/min per 1.73m2. MASTERPLAN (N = 505; 55 ESKD events) was used as development dataset, and NephroTest (N = 1385; 72 events) for validation. PREDICTORS: All models included age, sex, eGFR, and albuminuria, known prognostic markers for ESKD. ANALYTICAL APPROACH: We trained the models on the MASTERPLAN data and determined discrimination and calibration for each model at 2 years follow-up for a prediction horizon of 2 years in the NephroTest cohort. We benchmarked the predictive performance against the Kidney Failure Risk Equation (KFRE). RESULTS: The C-statistics for the KFRE was 0.94 (95%CI 0.86 to 1.01). Performance was similar for the Cox model with time-varying eGFR (0.92 [0.84 to 0.97]), eGFR (0.95 [0.90 to 1.00]), and the joint model 0.91 [0.87 to 0.96]). The Cox model with eGFR slope showed the best calibration. CONCLUSION: In the present studies, where the outcome was rare and follow-up data was highly complete, the joint models did not offer improvement in predictive performance over more traditional approaches such as a survival model with time-varying eGFR, or a model with eGFR slope.

Published
2019
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25. Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies

Author

Fan F Hou, Kimberly Smith, David Shepherd, William G. Herrington, Andrew S. Levey, Keiichi Sumida, Marc Froissart, Kazunobu Ichikawa, Jamie A. Green, Mila Tang, John Chalmers, Paul L Drury, Jack F.M. Wetzels, Misghina Weldegiorgis, Laura E Clark, Enyu Imai, Di Xie, John K Cuddeback, Gabriel Chodick, Gordon Prescott, Tom Greene, Julia B. Lewis, Sankar D. Navaneethan, Thorsten Vetter, Sadayoshi Ito, Kaleab Z. Abebe, Staffan Schön, Dick de Zeeuw, Ronald D. Perrone, Rajiv Nadukuru, C Yenchih Hsu, Carl-Gustaf Elinder, Stephen J Bakker, James F Medcalf, John F. Collins, Aliza Thompson, Fumiaki Kobayashi, Raina C Elley, Edmund J. Lewis, Richard D. Rohde, Brad C. Astor, Hirofumi Makino, Miklos Z. Molnar, Mark J. Sarnak, Abdul Rashid Qureshi, Roger A. Rodby, Hrefna Gudmundsdottir, Nigel J. Brunskill, Adeera Levin, Caroline S. Fox, Giuseppe Remuzzi, Hisatomi Arima, Varda Shalev, Arjan D. van Zuilen, Mårten Segelmark, Ognjenka Djurdjev, Margaret Smith, Simerjot K. Jassal, Sushrut S. Waikar, Nick Fluck, Joachim H. Ix, Barry M. Brenner, Mark Woodward, Kunihiro Matsushita, Chi Pang Wen, Kornelis Jj Van Hateren, Nanne Kleefstra, Jean-Philippe Haymann, Joseph V. Nally, Elizabeth L Ciemins, Henk J. G. Bilo, Lawrence J. Appel, Kerry Willis, Peter J. Blankestijn, Lesley A. Inker, Hans-Henrik Parving, Hiddo J.L. Heerspink, Luxia Zhang, Teresa K. Chen, Marie Evans, Areef Ishani, Girish N. Nadkarni, Pascal Houillier, Kai-Uwe Eckardt, Mitsumasa Umesawa, Jingsha Chen, Stein Hallan, Maria Stendahl, Corri Black, Robert G. Nelson, H. Lester Kirchner, Björn Runesson, Shoshana H. Ballew, Elizabeth Barrett-Connor, Angharad Marks, Ron T. Gansevoort, Martin Flamant, William C. Knowler, Jaclyn Bergstrom, Tsuneo Konta, Jan A.J.G. van den Brand, Stephen G Ellis, Marit Dahl Solbu, Lucia Kwak, Bénédicte Stengel, Alex R. Chang, Aditya Surapaneni, Jesse D. Schold, Shih-Jen Hwang, Marcello Tonelli, Juan Jesus Carrero, Tom Manley, Timothy Kenealy, Erwin P. Bottinger, Nikita Stempniewicz, Johan Ärnlöv, Rich Stempniewicz, Norman Stockbridge, Gijs W D Landman, Vlado Perkovic, Piero Ruggenenti, Marie Metzger, David Naimark, Josef Coresh, Lawrence G. Hunsicker, Kevin Ho, Solfrid Romundstad, Morgan E. Grams, Csaba P. Kovesdy, Atsushi Hirayama, Harold I. Feldman, Yingying Sang, Kevan R. Polkinghorne, Romaldas Maciulaitis, Navdeep Tangri, Rupert W. Major, Maneesh Sud, Groningen Kidney Center (GKC), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Cardiovascular Centre (CVC)

Subjects
SURROGATE, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Regression dilution, Renal function, 030209 endocrinology & metabolism, ALL-CAUSE, Kidney Function Tests, GLOMERULAR-FILTRATION-RATE, Article, APPROPRIATE THERAPEUTIC TARGET, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Internal medicine, Diabetes mellitus, CKD, medicine, Internal Medicine, Albuminuria, Humans, 030212 general & internal medicine, Surrogate endpoint, business.industry, urogenital system, MORTALITY, Hazard ratio, PROTEINURIA, medicine.disease, Prognosis, Diabetes and Metabolism, RENAL-DISEASE, Observational Studies as Topic, COLLABORATIVE METAANALYSIS, Cohort, Disease Progression, Kidney Failure, Chronic, medicine.symptom, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, POINT, Kidney disease, Glomerular Filtration Rate
Abstract

Item does not contain fulltext BACKGROUND: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. METHODS: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. FINDINGS: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0.83 (95% CI 0.74-0.94), decreasing to 0.78 (0.66-0.92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction

Published
2019

26. Increased PTH maintains bone mineral density in patients with CKD

Author

Martine Cohen-Solal, Agnès Ostertag, Marie Metzger, Pascal Houillier, Pablo Ureña Torres, Martin Flamant, and Pierre-Emmanuel Cailleaux

Subjects
Bone mineral, medicine.medical_specialty, lcsh:Diseases of the musculoskeletal system, Endocrinology, business.industry, Endocrinology, Diabetes and Metabolism, Internal medicine, Medicine, Orthopedics and Sports Medicine, In patient, lcsh:RC925-935, business
Published
2020
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27. Risk profile, quality of life and care of patients with moderate and advanced CKD : The French CKD-REIN Cohort Study

Author

Sophie Liabeuf, Ziad A. Massy, Bénédicte Stengel, Bruce M. Robinson, Jean-François Deleuze, Christophe Pascal, L. Frimat, Maurice Laville, Joost P. Schanstra, Serge Briançon, Marie Metzger, Karine Legrand, Carole Ayav, Céline Lange, Pascal Morel, Denis Fouque, Christian Combe, Elodie Speyer, Christian Jacquelinet, Yves-Edouard Herpe, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Bioingénierie tissulaire (BIOTIS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence de la biomédecine [Saint-Denis la Plaine], Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université de Lorraine (UL), Réseau Lorrain de prise en charge de l’insuffisance rénale chronique : Réseau NEPHROLOR (Nephrolor), Service de néphrologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Jean Moulin - Lyon 3 (UJML), Université de Lyon, Biobanque de Picardie [CHU Amiens - Hôpital Sud], CHU Amiens-Picardie, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Equipe 7 Inserm U1048, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Arbor Research Collaborative for Health, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de Néphrologie, Université Bordeaux Segalen - Bordeaux 2, Centre d'Investigation Clinique - Epidemiologie Clinique/essais Cliniques Nancy, Cancéropôle du Grand Est-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Réseau Lorrain de prise en charge de l’insuffisance rénale chronique : Réseau NEPHROLOR ( Nephrolor ), Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Transfert de gènes dans le foie : applications thérapeutiques, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire des sciences et techniques de l'information, de la communication et de la connaissance ( Lab-STICC ), École Nationale d'Ingénieurs de Brest ( ENIB ) -Université de Bretagne Sud ( UBS ) -Université de Brest ( UBO ) -Télécom Bretagne-Institut Brestois du Numérique et des Mathématiques ( IBNM ), Université de Brest ( UBO ) -Université européenne de Bretagne ( UEB ) -ENSTA Bretagne-Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Génotypage ( CNG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut de médecine moléculaire de Rangueil ( I2MR ), Université Paul Sabatier - Toulouse 3 ( UPS ) -IFR31-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Epidémiologie et Evaluations Cliniques [CHRU Nancy] ( Pôle S2R ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Centre de Recherche Clinique, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Chronic Kidney Disease - Réseau Epidémiologie et Information en Néphrologie (CKD REIN), Institut National de la Santé et de la Recherche Médicale (INSERM), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Nephrology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, Blood Pressure, 030204 cardiovascular system & hematology, urologic and male genital diseases, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Interquartile range, Internal medicine, Diabetes Mellitus, medicine, Albuminuria, Humans, Patient Reported Outcome Measures, Prospective Studies, Prospective cohort study, [ SHS.GESTION ] Humanities and Social Sciences/Business administration, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Transplantation, business.industry, Acute Kidney Injury, Middle Aged, Prognosis, medicine.disease, female genital diseases and pregnancy complications, 3. Good health, Proteinuria, Cardiovascular Diseases, Cohort, Quality of Life, Kidney Failure, Chronic, [SHS.GESTION]Humanities and Social Sciences/Business administration, Female, France, medicine.symptom, business, Glomerular Filtration Rate, Cohort study, Kidney disease
Abstract

International audience; Background: The French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study was designed to investigate the determinants of prognosis and care of patients referred to nephrologists with moderate and advanced chronic kidney disease (CKD). We examined their baseline risk profile and experience.Methods: We collected bioclinical and patient-reported information from 3033 outpatients with CKD and estimated glomerular filtration rates (eGFRs) of 15-60 mL/min/1.73 m2 treated at 40 nationally representative public and private facilities.Results: The patients' median age was 69 (60-76) years, 65% were men, their mean eGFR was 33 mL/min/1.73 m2, 43% had diabetes, 24% had a history of acute kidney injury (AKI) and 57% had uncontrolled blood pressure (BP; >140/90 mmHg). Men had worse risk profiles than women and were more likely to be past or current smokers (73% versus 34%) and have cardiovascular disease (59% versus 42%), albuminuria >30 mg/mmol (or proteinuria > 50) (40% versus 30%) (all P < 0.001) and a higher median risk of end-stage renal disease within 5 years, predicted by the kidney failure risk equation {12% [interquartile range (IQR) 3-37%] versus 9% [3-31%], P = 0.008}. During the previous year, 60% of patients reported one-to-two nephrologist visits and four or more general practitioner visits; only 25% saw a dietician and 75% were prescribed five or more medications daily. Physical and mental quality of life (QoL) were poor, with scores

Published
2018
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29. Urinary ammonia and long-term outcomes in chronic kidney disease

Author

Bénédicte Stengel, Jean-Jacques Boffa, Jean-Philippe Haymann, Marion Vallet, Martin Flamant, Marc Froissart, Pascal Houillier, François Vrtovsnik, Cédric Gauci, Eric Thervet, and Marie Metzger

Subjects
Male, metabolic acidosis, medicine.medical_specialty, Time Factors, Urinary system, Urology, Renal function, urologic and male genital diseases, Article, Excretion, Ammonia, Internal medicine, medicine, Humans, Prospective Studies, Renal Insufficiency, Chronic, Prospective cohort study, Aged, business.industry, Incidence, Hazard ratio, Metabolic acidosis, Odds ratio, Carbon Dioxide, Middle Aged, medicine.disease, Survival Rate, Cross-Sectional Studies, nutrition, Endocrinology, Nephrology, Disease Progression, Kidney Failure, Chronic, Female, France, business, Biomarkers, chronic kidney disease, Glomerular Filtration Rate, Kidney disease
Abstract

Recent studies suggest that alkalinizing treatments improve the course of chronic kidney disease (CKD), even in patients without overt metabolic acidosis. Here, we tested whether a decreased ability in excreting urinary acid rather than overt metabolic acidosis may be deleterious to the course of CKD. We studied the associations between baseline venous total CO 2 concentration or urinary ammonia excretion and long-term CKD outcomes in 1065 patients of the NephroTest cohort with CKD stages 1–4. All patients had measured glomerular filtration rate (mGFR) by 51 Cr-EDTA renal clearance. Median mGFR at baseline was 37.6 ml/min per 1.73 m 2 . Urinary ammonia excretion decreased with GFR, whereas net endogenous acid production did not. After a median follow-up of 4.3 years, 201 patients reached end-stage renal disease (ESRD) and 114 died before ESRD. Twenty-six percent of the patients had mGFR decline rate greater than 10% per year. Compared with patients in the highest tertile of urinary ammonia excretion, those in the lowest tertile had a significantly increased hazard ratio for ESRD, 1.82 (95% CI, 1.06–3.13), and a higher odds ratio of fast mGFR decline, 1.84 (0.98–3.48), independent of mGFR and other confounders. Patients in the lowest tertile of venous total CO 2 had significantly increased risk of fast mGFR decline but not of ESRD. None of these biomarkers was associated with mortality. Thus, these results suggest that the inability to excrete the daily acid load is deleterious to renal outcomes.

Published
2015
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30. Glycated Hemoglobin Level and Mortality in a Nondiabetic Population with CKD

Author

Jean-Philippe Haymann, Jean-Jacques Boffa, Claire Trivin, Martin Flamant, Pascal Houillier, Eric Thervet, Marie Metzger, François Vrtovsnik, and Bénédicte Stengel

Subjects
Male, medicine.medical_specialty, endocrine system diseases, Epidemiology, Population, urologic and male genital diseases, Critical Care and Intensive Care Medicine, chemistry.chemical_compound, Interquartile range, Internal medicine, medicine, Humans, Prediabetes, Renal Insufficiency, Chronic, Prospective cohort study, Intensive care medicine, education, Glycated Hemoglobin, Transplantation, education.field_of_study, business.industry, Hazard ratio, nutritional and metabolic diseases, Original Articles, medicine.disease, chemistry, Nephrology, Cohort, Female, Glycated hemoglobin, business, Cohort study
Abstract

Background and objectives Glycated hemoglobin (HbA 1c ) is used to diagnose diabetes mellitus (DM) and guide its management. The association between higher HbA 1c and progression to ESRD and mortality has been demonstrated in populations with DM. This study examined the association between HbA 1c and these end points in a population with CKD and without DM. Design, setting, participants, & measurements In the hospital-based NephroTest cohort study, measured GFR (mGFR) was taken by 51 Cr-EDTA renal clearance and HbA 1c in 1165 adults with nondialysis CKD stages 1–5 and without DM between January 2000 and December 2010. The median follow-up was 3.48 years (interquartile range, 1.94–5.82) for the competing events of ESRD and pre-ESRD mortality. Time-fixed and time-dependent Cox models were used to estimate hazard ratios (HRs) for ESRD and mortality according to HbA 1c , treated continuously or in tertiles. Results At inclusion, the mean mGFR was 42.2±19.9 ml/min per 1.73 m 2 , and the mean HbA 1c value was 5.5%±0.5%. During follow-up, 109 patients died, and 162 patients reached ESRD. Pre-ESRD mortality was significantly associated with HbA 1c treated continuously: for every 1% higher HbA 1c , the crude HR was 2.16 (95% confidence interval [95% CI], 1.27 to 3.68), and it was 1.85 (95% CI, 1.05 to 3.24) after adjustment for mGFR and other risk factors of death. After excluding incident diabetes over time, the updated mean of HbA 1c remained significantly associated with higher mortality risk: adjusted HR for the highest (5.7%–6.4%) versus the lowest tertile ( Conclusions In a CKD cohort, HbA 1c values in the prediabetes range are associated with mortality. Such values should be therefore included among the risk factors for negative outcomes in CKD populations.

Published
2015
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31. Oxidized LDL, statin use, morbidity, and mortality in patients receiving maintenance hemodialysis

Author

Graciela E. Delgado, Bénédicte Stengel, Winfried März, Bengt Fellström, Marie Metzger, Mugurel Apetrii, Sandra Wagner, Roland E. Schmieder, Marcus E. Kleber, Alan G. Jardine, Patrick Rossignol, Hubert Scharnagel, Faiez Zannad, Hallvard Holdaas, and Ziad A. Massy

Subjects
medicine.medical_specialty, Statin, medicine.drug_class, Population, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, AURORA trial, Internal medicine, medicine, Humans, Rosuvastatin, Rosuvastatin Calcium, education, Aged, Proportional Hazards Models, education.field_of_study, Proportional hazards model, business.industry, Hazard ratio, General Medicine, Middle Aged, Combined Modality Therapy, Lipoproteins, LDL, Oxidative Stress, Cardiovascular Diseases, Cardiology, Physical therapy, Kidney Failure, Chronic, lipids (amino acids, peptides, and proteins), Hydroxymethylglutaryl-CoA Reductase Inhibitors, business, Biomarkers, Mace, medicine.drug
Abstract

Statin treatment reduces the risk of cardiovascular mortality in the general population, but it has little or no benefit in hemodialyzed (HD) patients. This may reflect different underlying pathophysiology of cardiovascular disease (CVD) in patients treated with HD, maybe involving the oxidative stress. Our aim was to assess the association of oxidized low-density lipoprotein (oxLDL), determined by Mercodia oxLDL enzyme-linked immunosorbent assay (ELISA) kit, with major adverse cardiac events (MACE) and all-cause mortality in HD patients based on the AURORA trial (rosuvastatin vs placebo), and patients not on HD from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We also assessed whether its decrease due to statin use improves these outcomes using Cox proportional hazard models. Baseline oxLDL level was 34.2 ± 13.8 U/L in AURORA and did not differ between treatment groups, and 74.6 ± 28.1 U/L in LURIC. Lower baseline oxLDL levels were associated with higher hazard ratios (HRs) for outcomes, but not anymore after adjusting for apolipoprotein B level in AURORA and was not related to mortality in LURIC. OxLDL levels decreased by 30.9% between baseline and 3 months in the statin-treated group and increased by 10.5% between 3 and 12 months. Nevertheless, oxLDL reduction was not significantly associated with adjusted HRs for MACE and for all-cause mortality. These results showed no association between oxLDL and MACE after adjustment on apolipoprotein B, which may relate to the properties of the method used for oxLDL. Our results also showed no benefit for oxLDL reduction by rosuvastatin on outcomes. Future clinical trials are needed to define the relative CVD risks and benefits of other modalities of oxidative stress modification in this population.

Published
2017
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32. Hypertension résistante et maladie rénale chronique : épidémiologie et pronostic

Author

Alexandre Seidowsky, Ziad A. Massy, Bénédicte Stengel, and Marie Metzger

Subjects
medicine.medical_specialty, education.field_of_study, business.industry, Population, medicine.disease, Obesity, Nephrology, Renal sympathetic denervation, Diabetes mellitus, Internal medicine, Epidemiology, medicine, Salt intake, Risk factor, business, education, Kidney disease
Abstract

The emergence of new effective therapeutic strategies for the treatment of resistant hypertension such as renal sympathetic denervation technique has lead to a renewed interest in the screening and assessment of prognosis of this specific entity which constitutes a subset of uncontrolled hypertension. Its prevalence is unknown, but estimated between 12 and 15% among hypertensive subjects from the general population. Several factors have been associated with the development of resistant hypertension, four of which are essential: age, diabetes, chronic kidney disease and vascular structural alteration. Excessive salt intake is also a risk factor for poorly controlled hypertension in patients with salt-dependent hypertension, and may participate to the genesis of resistant hypertension. Because of population ageing and increasing prevalence of diabetes, obesity and chronic kidney disease, the prevalence of resistant hypertension is expected to rise. A better understanding of its determinants and associated risks (such as chronic kidney disease) would identify high-risk groups that may benefit from extensive diagnosis work up and more specific treatments.

Published
2014
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33. Relation Between Circulating Levels of 25(OH) Vitamin D and Parathyroid Hormone in Chronic Kidney Disease: Quest for a Threshold

Author

Jean Philippe Haymann, Jean-Jacques Boffa, Pascal Houillier, Cédric Gauci, François Vrtovsnik, Martin Flamant, Marc Froissart, Pablo Ureña-Torres, Eric Thervet, Bénédicte Stengel, and Marie Metzger

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Population, Parathyroid hormone, Renal function, Context (language use), Severity of Illness Index, Biochemistry, vitamin D deficiency, Phosphates, Cohort Studies, Endocrinology, Internal medicine, Prevalence, medicine, Vitamin D and neurology, Humans, Prospective Studies, Renal Insufficiency, Chronic, education, Prospective cohort study, Aged, Calcifediol, 25-Hydroxyvitamin D 2, education.field_of_study, business.industry, Biochemistry (medical), Middle Aged, Vitamin D Deficiency, medicine.disease, Parathyroid Hormone, Practice Guidelines as Topic, Hypercalcemia, Calcium, Female, France, business, Glomerular Filtration Rate, Kidney disease
Abstract

Vitamin D deficiency is common in patients with chronic kidney disease (CKD). Current guidelines recommend treatment strategies in these patients similar to those for the general population, but the vitamin D nutritional status sufficient to prevent PTH levels from increasing in CKD is unknown. OBJECTIVE, MAIN OUTCOME MEASURE: Our aim was to study the relation between circulating PTH and 25(OH)D levels and to search for a 25(OH)D threshold associated with a significant PTH increase.In the hospital-referred NephroTest cohort study, we measured 25(OH)D, PTH, and glomerular filtration rate (mGFR) by ⁵¹Cr-EDTA renal clearance in 929 adult patients with nondialysis CKD stages 1 to 5 and no vitamin D supplementation. Patients' mean age was 60.1 ± 14.7 years; 71% were men, and 9% were black. Their median mGFR was 37.8 mL/min/1.73 m².We found a 25(OH)D threshold of 8 ng/mL with an upper limit of 20 ng/mL (95% confidence interval) by linear piecewise regression modeling of log-PTH for 25(OH)D adjusted for mGFR, age, race, and ionized calcium level. The smoothed curve confirmed that PTH concentration rose steeply when circulating 25(OH)D levels fell to less than 20 ng/mL.Spontaneous 25(OH)D levels greater than 20 ng/mL seem sufficient to control serum PTH in CKD patients. This result reinforces guidelines to supplement vitamin D only if less than 30 ng/mL.

Published
2013
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34. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Author

Peter Kovacs, Alan F. Wright, Stephen Turner, Michèle M. Sale, Siim Sõber, Janoš Terzić, Elin Org, Richard S. Cooper, Alena Stančáková, Jerome I. Rotter, W. H. Linda Kao, Albert Hofman, Andrew B. Singleton, Florian Kronenberg, Jianjun Liu, Nicole L. Glazer, Christopher W. Knouff, Jennifer L. Bragg-Gresham, Juha Karjalainen, Li Ching Chang, Benjamin J. Wright, Jacqueline C.M. Witteman, Martin G. Larson, Klaus Stark, Richard J. Rodeheffer, Sharon L.R. Kardia, Douglas M. Ruderfer, Sheila Ulivi, Madhumathi Rao, Andrew A. Hicks, Eva Brand, Viviane Nicaud, Stephen G. Ball, Anna Köttgen, Germaine C. Verwoert, Anders Hamsten, Nick Shrine, Uwe Völker, Stefan Kloiber, Stephen Hancock, Emelia J. Benjamin, Bok Ghee Han, Kenneth Rice, Mark Woodward, Veronique Vitart, Karl Andersen, Nicholas J. Wareham, Robert Roberts, Maja Barbalić, David Couper, Yukinori Okada, André G. Uitterlinden, Sekar Kathiresan, Leo-Pekka Lyytikäinen, Pankaj Arora, Tatijana Zemunik, David S. Siscovick, Simonetta Guarrera, Dawn M. Waterworth, Tatjana Stojakovic, Braxton D. Mitchell, Devin Absher, Carmen A. Peralta, Mika Kivimäki, Xueling Sim, Norihiro Kato, Philippe Froguel, Keith L. Keene, Donna K. Arnett, Naoyuki Kamatani, Tazeen H. Jafar, Idris Guessous, Gunnar Jacobs, Michael M. Hoffmann, Kari Stefansson, Christian Hengstenberg, Tomonori Okamura, Inga Prokopenko, Christina Willenborg, Peter S. Braund, Rainer Rettig, Francesco U.S. Mattace-Raso, Vikal Tripathy, F. Gerald R. Fowkes, Laura R. Loehr, Harry Campbell, Margherita Cavalieri, Olle Melander, Hao Mei, I. Mateo Leach, Nicholette D. Palmer, Eva Albrecht, Naoharu Iwai, Stefan Martin Brand, Toshiko Tanaka, Jackie A. Cooper, Omri Gottesman, Manuela Uda, Angelo Scuteri, Aroon D. Hingorani, Cristiano Fava, Yusuke Nakamura, Jiang He, Min Jin Go, Serge Hercberg, Wendy L. McArdle, Philipp S. Wild, Florian Ernst, Paul Mitchell, Wolfgang Koenig, Caroline S. Fox, S. J.Cathy Fann, Janine F. Felix, Anna F. Dominiczak, Mike A. Nalls, Erik Ingelsson, Mario A. Morken, Susana Eyheramendy, Christopher Newton-Cheh, Igor Rudan, D. G. Vinay, Christopher P. Nelson, Ervin R. Fox, Xiuqing Guo, Jing Hua Zhao, Rick Twee-Hee Ong, Margaret M. Redfield, Oscar H. Franco, Yongmei Liu, Fulvio Ricceri, Mark A. Hlatky, Bernhard Paulweber, Mingyao Li, Themistocles L. Assimes, Karl Winkler, Inês Barroso, Sylvia E. Rosas, M Walker, Richard W Morris, Bo Hedblad, Hakon Hakonarson, Sonny Dandona, Peter H. Whincup, Martin Adam, Vilmundur Gudnason, Daniel Ackermann, Qiong Yang, Cuno S. P. M. Uiterwaal, Paul M. Ridker, George Davey Smith, Li Chen, C. Sinning, Terri L. Young, Jer-Yuarn Wu, Walter Palmas, Will Longstreth, Joe Devaney, Pavel Hamet, Xiaofeng Zhu, Fredrik Nyberg, Wilfried Renner, Anuj Goel, L. Adrienne Cupples, Nish Chaturvedi, Iftikhar J. Kullo, Nicholas D. Hastie, Aude Saint-Pierre, Panos Deloukas, Smita R. Kulkarni, Eric Boerwinkle, Wolfram Goessling, Gian Andri Thun, Eric J.G. Sijbrands, Shih-Jen Hwang, Carole Proust, Hirotsugu Ueshima, Kristian Hveem, Pierre Meneton, Joshua C. Denny, Olivier Devuyst, Kerri L. Wiggins, Ming-Huei Chen, Robert W. Lawrence, Robert L. Wilensky, Andre Franke, Nicole Soranzo, Simon Heath, Margot Haun, Karlhans Endlich, David Altshuler, Harald Grallert, Laurence Tiret, Luigi Ferrucci, Caroline Hayward, Sudha Seshadri, Bénédicte Stengel, Lynne E. Wagenknecht, John Attia, Andreas Ziegler, Renate B. Schnabel, Stefan Schreiber, Santosh Dahgam, Kurt Lohman, Christian M. Shaffer, Barbara Ludwig, Katalin Susztak, Chien-Hsiun Chen, Michele K. Evans, Paolo Vineis, Guo Li, Thomas J. Wang, Meena Kumari, Heather M. Stringham, Bruce M. Psaty, Norman Klopp, Halit Ongen, Ben A. Oostra, Stefan Coassin, Petra Bruse, Wei-Min Chen, Unnur Thorsteinsdottir, Charles N. Rotimi, Robert J. Carroll, Muredach P. Reilly, Niek Verweij, Dena G. Hernandez, Amy J. Swift, Barbara Kollerits, Hyung Lae Kim, Cristian Pattaro, Ivana Kolcic, Ronit Katz, John M. C. Connell, Dan E. Arking, Albert W. Dreisbach, Peter Vollenweider, C. S. Janipalli, Jian'an Luan, Erkki Vartiainen, James T. Willerson, John R. Thompson, Daniela Toniolo, Lyle J. Palmer, Alexander Teumer, Serkalem Demissie-Banjaw, Stella Trompet, James E. Hixson, Sue Shaw-Hawkins, Rossella Sorice, Bernhard R. Winkelmann, John Danesh, Anthony J. Balmforth, Toshio Ogihara, Jyotika K. Fernandes, Ulf Gyllensten, Ville Aalto, Åsa Johansson, Andres Metspalu, John F. Peden, Diana Kuh, Medea Imboden, Antonio Lupo, Su Chi Lim, Young-Jin Kim, Giovanni Malerba, Yurii S. Aulchenko, Satoshi Umemura, Ioanna Tzoulaki, Alan B. Weder, Helena Schmidt, Gerjan Navis, Susan R. Heckbert, Hans J. Rupprecht, Edward G. Lakatta, Christian Gieger, Najaf Amin, Paul Muntner, Lenore J. Launer, Ivana Persico, Hugh Watkins, Ian Ford, K. Radha Mani, Sylvia Stracke, Johanna Kuusisto, John Chalmers, Muhammad Islam, Lars Lind, Stefan R. Bornstein, Marjo-Riitta Järvelin, J. H. Young, Reiner Biffar, Santhi K. Ganesh, Kazuhiko Yamamoto, Annette Peters, Linda S. Adair, Tõnu Esko, Rebecca Hardy, Olga Jarinova, Antonietta Robino, Ruth McPherson, Benjamin F. Voight, Anne U. Jackson, Gang Shi, Stefania Bandinelli, Peter J. van der Most, John S. Gottdiener, Ying A. Wang, Mariza de Andrade, Joshua C. Bis, Leslie J. Raffel, Man Li, Jemma C. Hopewell, Bernhard O. Böhm, Aaron R. Folsom, Noël P. Burtt, S. Sidney, Diana Zelenika, Yuri Milaneschi, Pilar Galan, Iris M. Heid, Bernhard K. Krämer, Jean-Michel Gaspoz, Lynda M. Rose, Massimiliano Cocca, Jaap W. Deckers, Martin Farrall, Kent D. Taylor, Albert V. Smith, Candace Guiducci, Alan R. Shuldiner, Shiro Maeda, Liming Qu, Marilyn C. Cornelis, Xiaoling Wang, Daniel Shriner, Jutta Palmen, Yingchang Lu, Heyo K. Kroemer, Pio D'Adamo, Stephan J. L. Bakker, Tamara B. Harris, Myriam Rheinberger, Tetsuro Miki, Audrey Y. Chu, Ramachandran S. Vasan, Fuu Jen Tsai, Jan A. Staessen, Daniel I. Chasman, Jan Stritzke, Jasmin Divers, Meredith C. Foster, Jeanette M. Stafford, Maksim Struchalin, Arne Schillert, Jacques S. Beckmann, Mark E. Cooper, Jean-Charles Lambert, Mario Pirastu, Katja Butterbach, Carl G. P. Platou, Yan V. Sun, Marcus Fischer, Maciej Tomaszewski, Karl Werdan, Peng Chen, Daniel J. Rader, Thomas Münzel, Lowell F. Satler, Tom R. Gaunt, Brenda W.J.H. Penninx, William H. Matthai, John Whitfield, Rita P.S. Middelberg, Margus Viigimaa, Toshihiro Tanaka, Ida Yii Der Chen, Morris J. Brown, Valur Emilsson, J. Viikari, Wolfgang Lieb, Stephen E. Epstein, Harald Dobnig, Aravinda Chakravarti, Patrick Linsel-Nitschke, Stefan Pilz, Angela Doering, Sarah H. Wild, Patricia B. Munroe, Megan E. Rudock, Nicole Probst-Hensch, Danish Saleheen, Diederick E. Grobbee, Anke Tönjes, Narisu Narisu, Annika Rosengren, Masato Isono, Catherine Helmer, M. J.Kranthi Kumar, Alanna C. Morrison, Kay-Tee Khaw, Tanja Zeller, Jeffrey R. O'Connell, Christian Müller, Georg Homuth, Giriraj R. Chandak, Pankaj Sharma, Marcus Dörr, Veikko Salomaa, Paul F. 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Linda, Fox, Caroline S., RS: CARIM - R1.06 - Genetic Epidemiology and Genomics of cardiovascular diseases, Biochemie, RS: FHML MaCSBio, Ehret, Georg Benedikt, Guessous, Idris, Gaspoz, Jean-Michel, Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Polymer Chemistry and Bioengineering, Value, Affordability and Sustainability (VALUE), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology, Public Health, Internal Medicine, Clinical Genetics, Erasmus MC other, Genetic Identification, ICBP Consortium, AGEN Consortium, CHARGe-Heart Failure Group, ECHOGen Consortium, CARDIOGRAM, Abecasis, GR., Adair, LS., Alexander, M., Altshuler, D., Amin, N., Arking, DE., Arora, P., Aulchenko, Y., Bakker, SJ., Bandinelli, S., Barroso, I., Beckmann, JS., Beilby, JP., Bergman, RN., Bergmann, S., Bis, JC., Boehnke, M., Bonnycastle, LL., Bornstein, SR., Bots, ML., Bragg-Gresham, JL., Brand, SM., Brand, E., Braund, PS., Brown, MJ., Burton, PR., Casas, JP., Caulfield, MJ., Chakravarti, A., Chambers, JC., Chandak, GR., Chang, YP., Charchar, FJ., Chaturvedi, N., Shin Cho, Y., Clarke, R., Collins, FS., Collins, R., Connell, JM., Cooper, JA., Cooper, MN., Cooper, RS., Corsi, AM., Dörr, M., Dahgam, S., Danesh, J., Davey Smith, G., Day, IN., Deloukas, P., Denniff, M., Dominiczak, AF., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, FG., Fox, ER., Frayling, TM., Galan, P., Ganesh, SK., Garcia, M., Gaunt, TR., Glazer, NL., Go, MJ., Goel, A., Grässler, J., Grobbee, DE., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, BG., Hardy, R., Hartikainen, AL., Heath, S., Heckbert, SR., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, AA., Hilton, G., Hingorani, AD., Bolton, JA., Hopewell, JC., Howard, P., Humphries, SE., Hunt, SC., Hveem, K., Ikram, MA., Islam, M., Iwai, N., Jarvelin, MR., Jackson, AU., Jafar, TH., Janipalli, CS., Johnson, T., Kathiresan, S., Khaw, KT., Kim, HL., Kinra, S., Kita, Y., Kivimaki, M., Kooner, JS., Kumar, MJ., Kuh, D., Kulkarni, SR., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, EG., Langefeld, CD., Larson, MG., Lathrop, M., Lawlor, DA., Lawrence, RW., Lee, JY., Lee, NR., Levy, D., Li, Y., Longstreth, WT., Luan£££Jian'an£££ J., Lucas, G., Ludwig, B., Mangino, M., Mani, KR., Marmot, MG., Mattace-Raso, FU., Matullo, G., McArdle, WL., McKenzie, CA., Meitinger, T., Melander, O., Meneton, P., Meschia, JF., Miki, T., Milaneschi, Y., Mohlke, KL., Mooser, V., Morken, MA., Morris, RW., Mosley, TH., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, KD., Nilsson, P., Nyberg, F., O'Donnell, CJ., Ogihara, T., Ohkubo, T., Okamura, T., Ong, RT., Ongen, H., Onland-Moret, NC., O'Reilly, PF., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, LJ., Palmer, ND., Parker, AN., Peden, JF., Peltonen, L., Perola, M., Pihur, V., Platou, CG., Plump, A., Prabhakaran, D., Psaty, BM., Raffel, LJ., Rao, DC., Rasheed, A., Ricceri, F., Rice, KM., Rosengren, A., Rotter, JI., Rudock, ME., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, NJ., Schwartz, SM., Schwarz, PE., Scott, LJ., Scott, J., Scuteri, A., Sehmi, JS., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, NR., Sijbrands, EJ., Sim, X., Singleton, A., Sjögren, M., Smith, NL., Soler Artigas, M., Spector, TD., Staessen, JA., Stancakova, A., Steinle, NI., Strachan, DP., Stringham, HM., Sun, YV., Swift, AJ., Tabara, Y., Tai, ES., Talmud, PJ., Taylor, A., Terzic, J., Thelle, DS., Tobin, MD., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, CS., Umemura, S., van der Harst, P., van der Schouw YT., van Gilst WH., Vartiainen, E., Vasan, RS., Veldre, G., Verwoert, GC., Viigimaa, M., Vinay, DG., Vineis, P., Voight, BF., Vollenweider, P., Wagenknecht, LE., Wain, LV., Wang, X., Wang, TJ., Wareham, NJ., Watkins, H., Weder, AB., Whincup, PH., Wiggins, KL., Witteman, JC., Wong, A., Wu, Y., Yajnik, CS., Yao, J., Young, JH., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, JH., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, JY., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, SC., Wong, TY., Liu, J., Young, TL., Aung, T., Teo, YY., Kim, YJ., Kang, D., Chen, CH., Tsai, FJ., Chang, LC., Fann, SJ., Mei, H., Hixson, JE., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, YT., Tanaka, T., Reilly, MP., Schunkert, H., Assimes, TL., Hall, A., Hengstenberg, C., König, IR., Laaksonen, R., McPherson, R., Thompson, JR., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, LA., Halperin, E., Li, M., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, GA., Holm, H., Roberts, R., Stewart, AF., Fortmann, S., Go, A., Hlatky, M., Iribarren, C., Knowles, J., Myers, R., Quertermous, T., Sidney, S., Risch, N., Tang, H., Blankenberg, S., Schnabel, R., Sinning, C., Lackner, KJ., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, HJ., Perret, C., Proust, C., Münzel, TF., Barbalic, M., Chen, IY., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, KD., Volcik, K., Gretarsdottir, S., Gulcher, JR., Kong, A., Stefansson, K., Thorgeirsson, G., Andersen, K., Fischer, M., Grosshennig, A., Linsel-Nitschke, P., Stark, K., Schreiber, S., Aherrahrou, Z., Bruse, P., Doering, A., Klopp, N., Diemert, P., Loley, C., Medack, A., Nahrstedt, J., Peters, A., Wagner, AK., Willenborg, C., Böhm, BO., Dobnig, H., Grammer, TB., Hoffmann, MM., Meinitzer, A., Winkelmann, BR., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., Gabriel, SB., Dandona, S., Jarinova, O., Qu, L., Wilensky, R., Matthai, W., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Epstein, SE., Rader, DJ., Nelson, CP., Wright, BJ., Balmforth, AJ., Ball, SG., Loehr, LR., Rosamond, WD., Benjamin, E., Haritunians, T., Couper, D., Murabito, J., Wang, YA., Stricker, BH., Chang, PP., Willerson, JT., Felix, SB., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, RJ., Greiser, KH., Deckers, JW., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, MM., Werdan, K., Mitchell, GF., Arnett, DK., Gottdiener, JS., Blettner, M., and Friedrich, N.

Subjects
0301 basic medicine, Nephrology, Genetics and Molecular Biology (all), estimated glomerular filtration rate, estimated glomerular filtration rate, chronic kidney disease, genetic determinants, General Physics and Astronomy, Kidney development, Genome-wide association study, Biochemistry, Settore MED/14 - NEFROLOGIA, Renal Insufficiency, Chronic, Genetics, AGEN Consortium, ddc:616, education.field_of_study, Kidney, Stage renal-disease, Multidisciplinary, Genome-wide association, CHARGe-Heart Failure Group, Gene Expression Regulation, Genome-Wide Association Study, Genotype, Humans, Renal Insufficiency, Chronic, Genetic Predisposition to Disease, Biochemistry, Genetics and Molecular Biology (all), Chemistry (all), Physics and Astronomy (all), Metaanalysis, Renal Insufficiency, Chronic/genetics, Biological sciences, Serum creatinine, medicine.anatomical_structure, Efficient, Ronyons -- Fisiologia, Hypertension, ICBP Consortium, Transmembrane transporter activity, genetic association, loci, kidney function, CARDIOGRAM, Human, medicine.medical_specialty, Science, Population, Renal function, ECHOGen Consortium, Replication, Biology, Environment, Research Support, General Biochemistry, Genetics and Molecular Biology, N.I.H, genetic determinants, 03 medical and health sciences, GENOME-WIDE ASSOCIATION, FALSE DISCOVERY RATES, STAGE RENAL-DISEASE, SERUM CREATININE, METAANALYSIS, VARIANTS, INDIVIDUALS, POPULATION, RISK, HYPERTENSION, Kidney function, Research Support, N.I.H., Extramural, Internal medicine, MD Multidisciplinary, medicine, Journal Article, eGFRcrea, eGFRcys, ddc:610, Genetik, Mortality, education, ddc:613, urogenital system, Individuals, Extramural, General Chemistry, ta3121, medicine.disease, R1, 030104 developmental biology, 570 Life sciences, biology, Genètica, chronic kidney disease, Kidney disease, Meta-Analysis
Abstract

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways. J.T. and P.H. are consultants for Servier. J.C. received research grants and honoraria from Servier. K.S. obtained research support from Boehringer Ingelheim. The remaining authors declared no competing financial interests.

Published
2016
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35. Epidemiology of Vitamin D Deficiency in Chronic Kidney Disease

Author

Bénédicte Stengel and Marie Metzger

Subjects
medicine.medical_specialty, education.field_of_study, business.industry, medicine.medical_treatment, Population, medicine.disease, Gastroenterology, vitamin D deficiency, Internal medicine, Diabetes mellitus, medicine, Vitamin D and neurology, Albuminuria, Risk factor, medicine.symptom, education, business, Dialysis, Kidney disease
Abstract

Vitamin D deficiency is common in both the general population and CKD patients. Currently defined as a circulating 25-dihydroxyvitamin D (25(OH)D) level below 20 ng/mL (50 nmol/L), it is a major risk factor for bone and mineral disorders and has been related to increased risk of non-skeletal health outcomes including mortality, diabetes, and cardiovascular disease. A greater prevalence of this deficiency is expected in patients with CKD because they are older and more likely to have dark skin, obesity, and associated comorbidities such as diabetes and hypertension. In studies of clinical populations, the mean circulating 25(OH)D levels ranged from 18 to 29 ng/mL for patients with non-end-stage CKD and from 12 to 32 ng/mL for those on dialysis. Large population-based and clinical studies, however, describe inconsistent findings about the association between kidney function and vitamin D level. While some studies report significant, positive, and independents associations between glomerular filtration rate and circulating 25(OH)D values, others show low levels only in advanced CKD stages. Still others show no or even an inverse association, with paradoxically higher levels of 25(OH)D in individuals with moderate CKD than in those without CKD. Similarly, it remains unclear whether these discordant relations are direct and causal, or indirect because of confounders. Only a few studies have examined the relations between proteinuria or albuminuria and circulating 25(OH)D levels; they generally report significant negative associations. Potential mechanisms supporting a causal relation between kidney function and damage and vitamin D are discussed at the end of this chapter.

Published
2016
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36. Low Serum Creatine Kinase Level Predicts Mortality in Patients with a Chronic Kidney Disease

Author

Adrien Flahault, Marie Metzger, Jean-François Chassé, Jean-Philippe Haymann, Jean-Jacques Boffa, Martin Flamant, François Vrtovsnik, Pascal Houillier, Bénédicte Stengel, Eric Thervet, Nicolas Pallet, NephroTest study group, Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche en épidémiologie et santé des populations (CESP), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris Descartes - Paris 5 (UPD5), Dpt Clinical chemistry [CHU Pompidou], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie et Dialyses [CHU Tenon], Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Service d'explorations fonctionnelles [CHU Pompidou], Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre interdisciplinaire de recherche en biologie ( CIRB ), Collège de France ( CdF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), CHU Tenon [APHP]-Assistance publique - Hôpitaux de Paris - AP-HP (FRANCE), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 )

Subjects
[ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Male, Physiology, 030232 urology & nephrology, lcsh:Medicine, Blood Pressure, 030204 cardiovascular system & hematology, Biochemistry, Vascular Medicine, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cohort Studies, chemistry.chemical_compound, Endocrinology, 0302 clinical medicine, Chronic Kidney Disease, Medicine and Health Sciences, lcsh:Science, Creatine Kinase, 2. Zero hunger, education.field_of_study, Multidisciplinary, Hazard ratio, Drugs, Middle Aged, Nephrology, Creatinine, Female, Research Article, Glomerular Filtration Rate, medicine.medical_specialty, Endocrine Disorders, Death Rates, Population, Renal function, 03 medical and health sciences, Population Metrics, Albumins, Internal medicine, Diabetes Mellitus, medicine, Humans, Risk factor, education, Serum Albumin, Aged, Proportional Hazards Models, Demography, Pharmacology, Renal Physiology, Population Biology, Proportional hazards model, business.industry, lcsh:R, Statins, Biology and Life Sciences, Proteins, medicine.disease, chemistry, Metabolic Disorders, People and Places, Kidney Failure, Chronic, lcsh:Q, business, Body mass index, Biomarkers, Kidney disease
Abstract

NephroTest study group; International audience; BackgroundSerum creatine kinase (sCK) reflects CK activity from striated skeletal muscle. Muscle wasting is a risk factor for mortality in patients with chronic kidney disease (CKD). The aim of this study is to evaluate whether sCK is a predictor of mortality and end-stage renal disease (ESRD) in a CKD population.MethodsWe included 1801 non-dialysis-dependent CKD patients from the NephroTest cohort. We used time-fixed and time-dependent cause-specific Cox models to estimate hazard ratios (HRs) for the risk of death and for the risk of ESRD associated with gender-specific sCK tertiles.ResultsHigher sCK level at baseline was associated with a lower age, a higher body mass index, and a higher level of 24 h urinary creatinine excretion, serum albumin and prealbumin (p

Published
2016
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37. Association of Kidney Function, Vitamin D Deficiency, and Circulating Markers of Mineral and Bone Disorders in CKD

Author

Jean Philippe Haymann, Marie Metzger, Pascal Houillier, Martin Flamant, Cédric Gauci, Marc Froissart, Bénédicte Stengel, Alexandre Karras, Jean-Jacques Boffa, Pablo Ureña-Torres, and François Vrtovsnik

Subjects
Adult, medicine.medical_specialty, West Indies, Parathyroid hormone, Renal function, Comorbidity, Kidney, Collagen Type I, vitamin D deficiency, Cohort Studies, Hyperphosphatemia, Internal medicine, Prevalence, medicine, Vitamin D and neurology, Humans, Prospective Studies, Vitamin D, Africa South of the Sahara, Aged, Minerals, Hyperparathyroidism, business.industry, Orosomucoid, Middle Aged, Alkaline Phosphatase, Vitamin D Deficiency, medicine.disease, Bone Diseases, Metabolic, Cross-Sectional Studies, Endocrinology, Nephrology, Chronic Disease, Hyperparathyroidism, Secondary, Kidney Diseases, Secondary hyperparathyroidism, France, Peptides, business, Biomarkers, Glomerular Filtration Rate, Kidney disease
Abstract

Vitamin D (25 hydroxyvitamin D [25(OH)D]) deficiency is common in patients with chronic kidney disease (CKD). Neither the relation of this deficiency to the decrease in glomerular filtration rate (GFR) nor the effects on CKD mineral and bone disorders (MBD) are clearly established.Cross-sectional analysis of baseline data from a prospective cohort, the NephroTest Study.1,026 adult patients with all-stage CKD not on dialysis therapy or receiving vitamin D supplementation.For part 1, measured GFR (mGFR) using (51)Cr-EDTA renal clearance; for part 2, 25(OH)D deficiency at15 ng/mL.For part 1, 25(OH)D deficiency and several circulating MBD markers; for part 2, circulating MBD markers.For part 1, the prevalence of 25(OH)D deficiency was associated inversely with mGFR, ranging from 28%-51% for mGFR ≥60-15 mL/min/1.73 m(2). It was higher in patients of African origin; those with obesity, diabetes, hypertension, macroalbuminuria, and hypoalbuminemia; and during winter. After adjusting for these factors, ORs for 25(OH)D deficiency increased from 1.4 (95% CI, 0.9-2.3) to 1.4 (95% CI, 0.9-2.1), 1.7 (95% CI, 1.1-2.7), and 1.9 (95% CI, 1.1-3.6) as mGFR decreased from 45-59 to 30-44, 15-29, and15 (reference, ≥60) mL/min/1.73 m(2) (P for trend = 0.02). For part 2, 25(OH)D deficiency was associated with higher age-, sex-, and mGFR-adjusted ORs of ionized calcium level1.10 mmol/L (2.6; 95% CI, 1.2-5.9), 1,25 dihydroxyvitamin D concentration16.7 pg/mL (1.8; 95% CI, 1.3-2.4), hyperparathyroidism (1.8; 95% CI, 1.3-2.4), and serum C-terminal cross-linked collagen type I telopeptides concentration1,000 pg/mL (1.6; 95% CI, 1.0-2.6). It was not associated with hyperphosphatemia (phosphate1.38 mmol/L).Cross-sectional analysis of the data prevents causal inferences.25(OH)D deficiency is related independently to impaired mGFR. Both mGFR decrease and 25(OH)D deficiency are associated with abnormal levels of circulating MBD biomarkers.

Published
2011
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38. FP338EVALUATION OF THE ADEQUACY OF DRUG PRESCRIPTIONS IN PATIENTS WITH MODERATE OR ADVANCED CHRONIC KIDNEY DISEASE : RESULTS FROM THE FRENCH CKD-REIN COHORT

Author

Denis Fouque, Bénédicte Stengel, Christian Jacquelinet, Luc Frimat, Marie Metzger, Carole Ayav, Ziad A. Massy, Maurice Laville, Christian Combe, Sophie Liabeuf, Elodie Speyer, Bruce G. Robinson, and Solène M. Laville

Subjects
Drug, Transplantation, medicine.medical_specialty, business.industry, media_common.quotation_subject, medicine.disease, Nephrology, Internal medicine, Cohort, medicine, In patient, Medical prescription, business, media_common, Kidney disease
Published
2018
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39. Improved survival associated with acetate-free haemodialysis in elderly: a registry-based study

Author

Anne Kolko, Lucile Mercadal, Elisabeth Monnet, Christian Jacquelinet, Wenlun Yuan, Bénédicte Stengel, Marie Metzger, Jeanna-Eve Franck, and Thierry Hannedouche

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Hemodynamics, Comorbidity, Hemodiafiltration, Interquartile range, Internal medicine, Dialysis Solutions, medicine, Humans, Registries, Survival analysis, Dialysis, Acetic Acid, Aged, Aged, 80 and over, Transplantation, business.industry, Hazard ratio, Middle Aged, medicine.disease, Confidence interval, Hemodialysis Solutions, Surgery, Survival Rate, Nephrology, Kidney Failure, Chronic, Female, Hemodialysis, business
Abstract

Background Acetate-free dialysis (AFD) improves haemodynamic stability during dialysis, compared with standard haemodialysis (HD) with a small amount of acetic acid. Using the national REIN registry, we classified 15 160 incident patients who started HD from 2008 to 2010 into three exposure categories according to the type of dialysate used in their dialysis unit: standard dialysate only (reference), both standard and AFD (mixed unit) or HCl dialysate only (100% HCl unit). Methods Cox survival analysis was adjusted for 15 baseline comorbidities, laboratory data and haemodiafiltration (HDF). We took patient clustering within units into account, used age as the time scale and treated patient exposure to AFD and to HDF as time-dependent variables. Results Median age (interquartile range) was 70.5 years (58.1-78.8). Over a median follow-up of 1.8 years (1.2-2.6), 658 patients were dialysed in a 100% HCl unit, 3021 in a mixed unit and 11 481 were never exposed to AFD. The relation between AFD and mortality was not constant with age (Schoenfeld residuals test P = 0.01 for mixed group and P = 0.03 for 100%HCl group). Patients older than 70 years had a significantly lower mortality risk associated with AFD [hazard ratio (HR) = 0.79, 95% confidence interval (CI) = 0.67 to 0.94 for patients exposed in a 100% HCl unit; HR = 0.83, 95% CI = 0.74 to 0.94 for patients exposed in a mixed unit], but no association was found in younger patients. Conclusions AFD was associated with improved survival independent of comorbidities and HDF in patients aged 70 years and older but not in patient younger than 70 years.

Published
2015

40. Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

Author

Menno Pruijm, Thor Aspelund, Ruth J. F. Loos, Philipp S. Wild, Wolfgang Koenig, Ozren Polasek, Jacques S. Beckmann, Christa Meisinger, Aida Karina Dieffenbach, Jozef Lazar, Yi-An Ko, Lyudmyla Kedenko, Matthias Nauck, Thomas Illig, Alessandro Luciani, Christian Fuchsberger, Claudia Langenberg, Nan Cher Yeo, Bénédicte Stengel, Katalin Susztak, Karlhans Endlich, Linda T. Hiraki, Zoltán Kutalik, Nicole Endlich, Ronit Katz, Lenore J. Launer, Vladan Mijatovic, Gerjan Navis, Christian Gieger, Howard J. Jacob, Iris M. Heid, Mathias Gorski, David S. Siscovick, Bernhard K. Krämer, John Chalmers, Melanie Waldenberger, Peter Vollenweider, Nicole Soranzo, Igor Rudan, Ron T. Gansevoort, Jeffrey R. O'Connell, Christian Müller, Margot Haun, Joshua C. Denny, Olivier Devuyst, Rainer Rettig, Holly Kramer, Jian'an Luan, Tamara B. Harris, Marie Metzger, Christian M. Shaffer, Ming-Huei Chen, Giovanni Malerba, Reiner Biffar, Man Li, Josef Coresh, Harald Grallert, Belen Ponte, Ian H. de Boer, Barbara Kollerits, Myriam Rheinberger, Vincent Chouraki, Jean-Charles Lambert, Katja Butterbach, Albert V. Smith, Georg Ehret, Audrey Y. Chu, Antonio Lupo, Caroline S. Fox, Alan R. Shuldiner, Pavel Hamet, Shih-Jen Hwang, Yong Li, Sylvia E. Rosas, Daniel Taliun, Niek Verweij, Luigi Ferrucci, Uwe Völker, Braxton D. Mitchell, H Brenner, Sven Bergmann, Bernhard Paulweber, Matthew Hoffman, Sylvia Stracke, Rossella Sorice, Robert J. Carroll, Florian Kronenberg, Jing Hua Zhao, Qiong Yang, Johanne Tremblay, Peter P. Pramstaller, Vilmundur Gudnason, Murielle Bochud, Daniel Ackermann, Hans L. Hillege, Nicholas J. Wareham, Mark Woodward, Eric Boerwinkle, Uwe Lendeckel, Guo Li, Georg Homuth, I. Mateo Leach, Gudny Eiriksdottir, Cristian Pattaro, Andrew D. Paterson, Henry Völzke, Gérard Waeber, Carsten A. Böger, Giovanni Gambaro, Meredith C. Foster, Henri Wallaschofski, Adrienne Tin, Catherine Helmer, Bamidele O. Tayo, Matthias Olden, Anna Köttgen, Toshiko Tanaka, Caroline Hayward, Tanguy Corre, Stefan Coassin, Alexander Teumer, Tanja Zeller, H.-Erich Wichmann, Afshin Parsa, Allison Zappa, Pim van der Harst, Ponte, Belen, Ehret, Georg Benedikt, Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Vascular Ageing Programme (VAP), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), and Value, Affordability and Sustainability (VALUE)

Subjects
Male, 0301 basic medicine, diabetes, gene, Endocrinology, Diabetes and Metabolism, Genome-wide association study, Kidney, GLOMERULAR-FILTRATION-RATE, Cathepsin C, Gene Knockout Techniques, cubilin, Settore MED/14 - NEFROLOGIA, Diabetic Nephropathies, MODULATES PROTEINURIA, ddc:616, HERITABILITY, Diabetes, Genetics/Genomes/Proteomics/Metabolomics, Middle Aged, RISK POPULATION COHORTS, 3. Good health, INSIGHTS, Kidney Tubules, Female, Sulfotransferases, medicine.symptom, RAB38, Adult, EXPRESSION, medicine.medical_specialty, Renal function, Receptors, Cell Surface, 610 Medicine & health, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, albuminuria, Diabetes Mellitus, Experimental, 03 medical and health sciences, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Animals, Humans, Genetic Predisposition to Disease, Aged, MORTALITY, KIDNEY-DISEASE, medicine.disease, Cubilin, Rats, Minor allele frequency, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 2, rab GTP-Binding Proteins, COLLABORATIVE METAANALYSIS, Albuminuria, 570 Life sciences, biology, albuminuria, diabetes, cubilin, Genome-Wide Association Study, Kidney disease
Abstract

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10–7) and 13% for RAB38/CTSC (P = 5.8 × 10−7). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria.

Published
2015
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41. Predictors of nonfunctional arteriovenous access at hemodialysis initiation and timing of access creation: A registry-based study

Author

Christian Jacquelinet, Raphael Coscas, Bénédicte Stengel, Michel Labeeuw, Natalia Alencar de Pinho, Carole Ayav, Marie Metzger, and Ziad A. Massy

Subjects
Time Factors, Cardiovascular Procedures, medicine.medical_treatment, 030232 urology & nephrology, lcsh:Medicine, Vascular Surgery, Comorbidity, 030204 cardiovascular system & hematology, Pathology and Laboratory Medicine, Cohort Studies, Endocrinology, 0302 clinical medicine, Chronic Kidney Disease, Odds Ratio, Prevalence, Medicine and Health Sciences, Ethnicities, Registries, French People, lcsh:Science, Multidisciplinary, Catheter, Nephrology, Hemodialysis, Research Article, Biotechnology, Cohort study, medicine.medical_specialty, Catheters, Endocrine Disorders, Surgical and Invasive Medical Procedures, 03 medical and health sciences, Arteriovenous Shunt, Surgical, Signs and Symptoms, Renal Dialysis, Diagnostic Medicine, Internal medicine, Diabetes mellitus, Medical Dialysis, Diabetes Mellitus, Renal Diseases, medicine, Humans, Fistulas, Dialysis, business.industry, lcsh:R, Biology and Life Sciences, Odds ratio, medicine.disease, Confidence interval, Surgery, Metabolic Disorders, People and Places, lcsh:Q, Medical Devices and Equipment, Population Groupings, business
Abstract

Determinants of nonfunctional arteriovenous (AV) access, including timing of AV access creation, have not been sufficiently described. We studied 29 945 patients who had predialysis AV access placement and were included in the French REIN registry from 2005 through 2013. AV access was considered nonfunctional when dialysis began with a catheter. We estimated crude and adjusted odds ratio (OR) with 95% confidence intervals (CI) of nonfunctional versus functional AV access associated with case-mix, facility characteristics, and timing of AV access creation. Analyses were stratified by dialysis start condition (planned or as an emergency) and comorbidity profile. Overall, 18% patients had nonfunctional AV access at hemodialysis initiation. In the group with planned dialysis start, female gender (OR 1.43, 95% CI 1.32-1.56), diabetes (OR 1.28, 95% CI 1.15-1.44), and a higher number of cardiovascular comorbidities (OR 1.27, 95% CI 1.09-1.49, and 1.31, 1.05-1.64, for 3 and >3 cardiovascular comorbidities versus none, respectively) were independent predictors of nonfunctional AV access. A higher percentage of AV access creation at the region level was associated with a lower rate of nonfunctional AV access (OR 0.98, 95% CI 0.98-0.99 per 1% increase). The odds of nonfunctional AV access decreased as time from creation to hemodialysis initiation increased up to 3 months in nondiabetic patients with fewer than 2 cardiovascular comorbidities and 6 months in patients with diabetes or 2 or more such comorbidities. In conclusion, both patient characteristics and clinical practices may play a role in successful AV access use at hemodialysis initiation. Adjusting the timing of AV access creation to patients' comorbidity profiles may improve functional AV access rates.

Published
2017
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43. Decrease in urinary creatinine excretion in early stage chronic kidney disease

Author

Elena Tynkevich, Martin Flamant, Jean-Philippe Haymann, Marie Metzger, Eric Thervet, Jean-Jacques Boffa, François Vrtovsnik, Pascal Houillier, Marc Froissart, Bénédicte Stengel, NephroTest Study Group, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Physiologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 )

Subjects
[ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Male, Muscle Physiology, Physiology, Epidemiology, 030232 urology & nephrology, lcsh:Medicine, Urine, 030204 cardiovascular system & hematology, Kidney Function Tests, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Chronic Kidney Disease, Medicine and Health Sciences, Ethnicity, Medicine, Clinical Epidemiology, Public and Occupational Health, Prospective Studies, lcsh:Science, Musculoskeletal System, 2. Zero hunger, education.field_of_study, Multidisciplinary, Proteinuria, Muscles, Age Factors, Muscle Biochemistry, Organ Size, Nephrology, Creatinine, Female, Anatomy, medicine.symptom, Research Article, Glomerular Filtration Rate, medicine.medical_specialty, Urinary system, Population, Urology, Renal function, Excretion, 03 medical and health sciences, Sex Factors, Internal medicine, Humans, Renal Insufficiency, Chronic, Muscle, Skeletal, education, Nutrition, Renal Physiology, business.industry, Malnutrition, lcsh:R, Biology and Life Sciences, Renal System, medicine.disease, Biomarker Epidemiology, Endocrinology, chemistry, lcsh:Q, business, Kidney disease
Abstract

NephroTest Study Group; International audience; BACKGROUND:Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population.METHODS:We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by (51)Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time.RESULTS:Baseline mean urinary creatinine excretion decreased from 15.3 ± 3.1 to 12.1 ± 3.3 mmol/24 h (0.20 ± 0.03 to 0.15 ± 0.04 mmol/kg/24 h) in men, with mGFR falling from ≥ 60 to

Published
2014
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44. Should we use standard survival models or the illness-death model for interval-censored data to investigate risk factors of chronic kidney disease progression?

Author

Julie Boucquemont, Marie Metzger, Christian Combe, Bénédicte Stengel, Karen Leffondre, and NephroTest Study Group

Subjects
Oncology, Male, Pathology, Epidemiology, urologic and male genital diseases, Severity of Illness Index, chemistry.chemical_compound, Mathematical and Statistical Techniques, Risk Factors, Chronic Kidney Disease, Medicine and Health Sciences, Kidney transplantation, Multidisciplinary, Mortality rate, Middle Aged, Prognosis, 3. Good health, Death, Nephrology, Creatinine, Cohort, Physical Sciences, Disease Progression, Medicine, Female, Statistics (Mathematics), Glomerular Filtration Rate, Research Article, Adult, medicine.medical_specialty, Science, Renal function, Research and Analysis Methods, Internal medicine, Severity of illness, medicine, Humans, Renal Insufficiency, Chronic, Statistical Methods, Survival analysis, Aged, business.industry, medicine.disease, Kidney Transplantation, Survival Analysis, chemistry, business, Mathematics, Kidney disease
Abstract

BackgroundIn studies investigating risk factors of chronic kidney disease (CKD) progression, one may be interested in estimating factors effects on both a fall of glomerular filtration rate (GFR) below a specific level (i.e., a CKD stage) and death. Such studies have to account for the fact that GFR is measured at intermittent visit only, which implies that progression to the stage of interest is unknown for patients who die before being observed at that stage. Our objective was to compare the results of an illness-death model that handles this uncertainty, with frequently used survival models.MethodsThis study included 1,519 patients from the NephroTest cohort with CKD stages 1-4 at baseline (69% males, 59±15 years, median protein/creatinine ratio [PCR] 27.4 mg/mmol) and subsequent annual measures of GFR (follow-up time 4.3±2.7 years). Each model was used to estimate the effects of sex, age, PCR, and GFR at baseline on the hazards of progression to CKD stage 5 (GFRResultsFor progression to stage 5, there were only minor differences between results from the different models. The differences between results were higher for the hazard of death before or after progression. Our results also suggest that previous findings on the effect of age on end-stage renal disease are more likely due to a strong impact of age on death than to an effect on progression. The probabilities of progression were systematically under-estimated with the survival model as compared with the illness-death model.ConclusionsThis study illustrates the advantages of the illness-death model for accurately estimating the effects of risk factors on the hazard of progression and death, and probabilities of progression. It avoids the need to choose arbitrary time-to-event and time-to-censoring, while accounting for both interval censoring and competition by death, using a single analytical model.

Published
2014

45. The Relation of Hepcidin to Iron Disorders, Inflammation and Hemoglobin in Chronic Kidney Disease

Author

Bénédicte Stengel, François Vrtovsnik, Lucile Mercadel, Martin Flamant, Marie Metzger, Marc Froissart, Eric Thervet, Jean-Jacques Boffa, Jean Philippe Haymann, Pascal Houillier, Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM U699, Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL UPMC, Gestionnaire, Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Service d'urologie, néphrologie et transplantation [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de Physiologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 )

Subjects
Male, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Hemoglobins, 0302 clinical medicine, hemic and lymphatic diseases, Chronic Kidney Disease, Medicine and Health Sciences, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Anemia, Iron-Deficiency, biology, Anemia, Iron deficiency, Hematology, Middle Aged, 3. Good health, Nephrology, Medicine, Female, Research Article, Adult, medicine.medical_specialty, Science, Iron, Renal function, 03 medical and health sciences, Hepcidins, Hepcidin, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, medicine, Humans, Renal Insufficiency, Chronic, Iron Deficiency Anemia, Aged, Inflammation, Transferrin saturation, business.industry, Correction, medicine.disease, Hematopoiesis, Ferritin, Endocrinology, Iron-deficiency anemia, biology.protein, Hemoglobin, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

on behalf of the NephroTest Study Group; International audience; The metabolism of hepcidin is profoundly modified in chronic kidney disease (CKD). We investigated its relation to iron disorders, inflammation and hemoglobin (Hb) level in 199 non-dialyzed, non-transplanted patients with CKD stages 1–5. All had their glomerular filtration rate measured by 51 Cr-EDTA renal clearance (mGFR), as well as measurements of iron markers including hepcidin and of erythropoietin (EPO). Hepcidin varied from 0.2 to 193 ng/mL. The median increased from 23.3 ng/ mL [8.8–28.7] to 36.1 ng/mL [14.1–92.3] when mGFR decreased from $60 to ,15 mL/min/1.73 m 2 (p = 0.02). Patients with absolute iron deficiency (transferrin saturation (TSAT) ,20% and ferritin ,40 ng/mL) had the lowest hepcidin levels (5.0 ng/ mL [0.7–11.7]), and those with a normal iron profile (TSAT $20% and ferritin $40), the highest (34.5 ng/mL [23.7–51.6]). In multivariate analysis, absolute iron deficiency was associated with lower hepcidin values, and inflammation combined with a normal or functional iron profile with higher values, independent of other determinants of hepcidin concentration, including EPO, mGFR, and albuminemia. The hepcidin level, although it rose overall when mGFR declined, collapsed in patients with absolute iron deficiency. There was a significant interaction with iron status in the association between Hb and hepcidin. Except in absolute iron deficiency, hepcidin's negative association with Hb level indicates that it is not down-regulated in CKD anemia.

Published
2014
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46. A 3-Marker Index Improves the Identification of Iron Disorders in CKD Anaemia

Author

Lucile Mercadal, Marie Metzger, Jean Philippe Haymann, Eric Thervet, Jean-Jacques Boffa, Martin Flamant, François Vrtovsnik, Cédric Gauci, Marc Froissart, Bénédicte Stengel, NephroTest Study Group, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), INSERM U775, Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM U699, Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service d'Urologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'urologie, néphrologie et transplantation [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de Physiologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ), HAL UPMC, Gestionnaire, and Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon]

Subjects
Male, Epidemiology, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Red Cells, 030232 urology & nephrology, lcsh:Medicine, 030204 cardiovascular system & hematology, Kidney, Gastroenterology, Hemoglobins, 0302 clinical medicine, Total iron-binding capacity, Risk Factors, Chronic Kidney Disease, Clinical Epidemiology, lcsh:Science, chemistry.chemical_classification, Multidisciplinary, medicine.diagnostic_test, biology, Transferrin, Anemia, Iron deficiency, Hematology, Middle Aged, Nephrology, Medicine, Female, Research Article, Glomerular Filtration Rate, medicine.medical_specialty, Clinical Research Design, Iron, 03 medical and health sciences, Sex Factors, Hepcidin, Internal medicine, medicine, Humans, Renal Insufficiency, Chronic, Iron Deficiency Anemia, Biology, Aged, Population Biology, Transferrin saturation, business.industry, lcsh:R, medicine.disease, Ferritin, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, chemistry, Iron-deficiency anemia, Ferritins, biology.protein, lcsh:Q, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers
Abstract

on behalf of the NephroTest Study Group; International audience; BackgroundIron disorders are common and complex in chronic kidney disease (CKD). We sought to determine whether a 3-marker index would improve the classification of iron disorders in CKD anaemia.MethodsWe studied the association between Hb level and iron indexes combining 2 or 3 of the following markers: serum ferritin (

Published
2014
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47. Identifying subgroups of renal function trajectories

Author

Bénédicte Stengel, Lucie Loubère, Marie Metzger, Christian Combe, Karen Leffondré, and Julie Boucquemont

Subjects
medicine.medical_specialty, Iohexol, 030232 urology & nephrology, Renal function, PAH clearance, urologic and male genital diseases, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Humans, Medicine, Registries, 030212 general & internal medicine, Renal Insufficiency, Chronic, Sweden, Transplantation, Creatinine, Proteinuria, business.industry, Effective renal plasma flow, medicine.disease, chemistry, Nephrology, Cohort, medicine.symptom, business, Glomerular Filtration Rate, Cohort study, Kidney disease
Abstract

Background Renal function in patients with chronic kidney disease (CKD) may follow different trajectory profiles. The aim of this study was to evaluate and illustrate the ability of the latent class linear mixed model (LCMM) to identify clinically relevant subgroups of renal function trajectories within a multicenter hospital-based cohort of CKD patients. Methods We analysed data from the NephroTest cohort including 1967 patients with all-stage CKD at baseline who had glomerular filtration rate (GFR) both measured by 51 Cr-EDTA renal clearance (mGFR) and estimated by the CKD-EPI equation (eGFR); 1103 patients had at least two measurements. The LCMM was used to identify subgroups of GFR trajectories, and patients' characteristics at baseline were compared between the subgroups identified. Results Five classes of mGFR trajectories were identified. Three had a slow linear decline of mGFR over time at different levels. In the two others, patients had a high level of mGFR at baseline with either a strong nonlinear decline over time ( n = 11) or a nonlinear improvement ( n = 94) of mGFR. Higher levels of proteinuria and blood pressure at baseline were observed in classes with either severely decreased mGFR or strong mGFR decline over time. Using eGFR provided similar findings. Conclusion The LCMM allowed us to identify in our cohort five clinically relevant subgroups of renal function trajectories. It could be used in other CKD cohorts to better characterize their different profiles of disease progression, as well as to investigate specific risk factors associated with each profile.

Published
2016
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48. Kidney Function Decline and Apparent Treatment-Resistant Hypertension in the Elderly

Author

Marie Metzger, Christophe Tzourio, Ziad A. Massy, Bénédicte Stengel, Catherine Helmer, Jean Kaboré, and Claudine Berr

Subjects
Hypertension, Renal, Drug Resistance, 030232 urology & nephrology, lcsh:Medicine, Physiology, Blood Pressure, Comorbidity, Cardiovascular Medicine, 030204 cardiovascular system & hematology, Vascular Medicine, chemistry.chemical_compound, Endocrinology, Elderly, 0302 clinical medicine, Chronic Kidney Disease, Medicine and Health Sciences, Odds Ratio, Prevalence, lcsh:Science, Resistant Hypertension, Aged, 80 and over, Multidisciplinary, Age Factors, Drugs, Middle Aged, Causality, Antihypertensive Drugs, Nephrology, Cardiovascular Diseases, Creatinine, Hypertension, Disease Progression, Cardiology, Drug Therapy, Combination, France, Anatomy, medicine.symptom, Research Article, Glomerular Filtration Rate, medicine.medical_specialty, Endocrine Disorders, Hypercholesterolemia, Renal function, Sensitivity and Specificity, 03 medical and health sciences, Sex Factors, Diabetes mellitus, Internal medicine, Diabetes Mellitus, medicine, Albuminuria, Humans, Obesity, Renal Insufficiency, Chronic, Antihypertensive Agents, Aged, Pharmacology, business.industry, lcsh:R, Biology and Life Sciences, Kidneys, Renal System, Odds ratio, medicine.disease, chemistry, Age Groups, Metabolic Disorders, People and Places, lcsh:Q, Population Groupings, business, Follow-Up Studies, Kidney disease
Abstract

BACKGROUND:Cross-sectional studies show a strong association between chronic kidney disease and apparent treatment-resistant hypertension, but the longitudinal association of the rate of kidney function decline with the risk of resistant hypertension is unknown. METHODS:The population-based Three-City included 8,695 participants older than 65 years, 4265 of them treated for hypertension. We estimated the odds ratios (OR) of new-onset apparent treatment-resistant hypertension, defined as blood pressure ≥ 140/90 mmHg despite use of 3 antihypertensive drug classes or ≥ 4 classes regardless of blood pressure, associated with the mean estimated glomerular filtration rate (eGFR) level and its rate of decline over 4 years, compared with both controlled hypertension and uncontrolled nonresistant hypertension with ≤ 2 drugs. GFR was estimated with three different equations. RESULTS:Baseline prevalence of apparent treatment-resistant hypertension and of controlled and uncontrolled nonresistant hypertension, were 6.5%, 62.3% and 31.2%, respectively. During follow-up, 162 participants developed apparent treatment-resistant hypertension. Mean eGFR decline with the MDRD equation was 1.5±2.9 mL/min/1.73 m² per year: 27.7% of the participants had an eGFR ≥3 and 10.1% ≥ 5 mL/min/1.73 m² per year. After adjusting for age, sex, obesity, diabetes, and cardiovascular history, the ORs for new-onset apparent treatment-resistant hypertension associated with a mean eGFR level, per 15 mL/min/1.73 m² drop, were 1.23 [95% confidence interval 0.91-1.64] compared to controlled hypertension and 1.10 [0.83-1.45] compared to uncontrolled nonresistant hypertension; ORs associated with a decline rate ≥ 3 mL/min/1.73 m² per year were 1.89 [1.09-3.29] and 1.99 [1.19-3.35], respectively. Similar results were obtained when we estimated GFR with the CKDEPI and the BIS1 equations. ORs tended to be higher for an eGFR decline rate ≥ 5 mL/min/1.73 m² per year. CONCLUSION:The speed of kidney function decline is associated more strongly than kidney function itself with the risk of apparent treatment-resistant hypertension in the elderly.

Published
2016
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49. Large Artery Stiffening and Remodeling Are Independently Associated With All-Cause Mortality and Cardiovascular Events in Chronic Kidney Disease

Author

Philippe Guardiola, Marie Metzger, Marie Briet, Stéphane Laurent, Gérard Maruani, Pascal Houillier, Jean-Philippe Haymann, Marc Froissart, Bénédicte Stengel, Pierre Boutouyrie, Alexandre Karras, Erwan Bozec, Christian Jacquot, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), SNP, Transcriptome & Epigénomique [CHU Angers] (Plateforme STE), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CIC AP-HP (hegp Ex-Broussais)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM), and Univ Angers, Okina

Subjects
Adult, Carotid Artery Diseases, Male, medicine.medical_specialty, aortic stiffness, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, Blood Pressure, carotid artery common, 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, 03 medical and health sciences, 0302 clinical medicine, Vascular Stiffness, Internal medicine, Internal Medicine, medicine, Humans, Cumulative incidence, Renal Insufficiency, Renal Insufficiency, Chronic, Mortality, Prospective cohort study, Pulse wave velocity, Aged, business.industry, Middle Aged, medicine.disease, Prognosis, Remodeling, [SDV] Life Sciences [q-bio], Survival Rate, Cardiovascular Diseases, Relative risk, Arterial stiffness, Cardiology, Aortic stiffness, Female, business, Kidney disease, Glomerular Filtration Rate
Abstract

Chronic kidney disease, even at moderate stages, is characterized by a high incidence of cardiovascular events. Subclinical damage to large arteries, such as increased arterial stiffness and outward remodeling, is a classical hallmark of patients with chronic kidney disease. Whether large artery stiffness and remodeling influence the occurrence of cardiovascular events and the mortality of patients with chronic kidney disease (stages 2–5) is still debated. This prospective study included 439 patients with chronic kidney disease (mean age, 59.8±14.5 years) with a mean measured glomerular filtration rate of 37 mL/min per 1.73 m 2 . Baseline aortic stiffness was estimated through carotid-femoral pulse wave velocity measurements; carotid stiffness, diameter, and intima-media thickness were measured with a high-resolution echotracking system. For the overall group of patients, the 5-year estimated survival and cumulative incidence of cardiovascular events were 87% and 16%, respectively. In regression analyses adjusted on classical cardiovascular and renal risk factors, aortic stiffness remained significantly associated with all-cause mortality (for 1 SD, Cox model–derived relative risk [95% CI], 1.48 [1.09–2.02]) and with fatal and nonfatal cardiovascular events (for 1 SD, Fine and Gray competing risks model–derived relative risk [95% CI], 1.35 [1.05–1.75]). Net reclassification improvement index was significant (29.0% [2.3–42.0%]). Carotid internal diameter was also independently associated with all-cause mortality. This study shows that increased aortic stiffness and carotid internal diameter are independent predictors of mortality in patients with stages 2 to 5 chronic kidney disease and that aortic stiffness improves the prediction of the risk.

Published
2012
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50. Chronic kidney disease, cognitive decline, and incident dementia: the 3C Study

Author

Ziad A. Massy, Claudine Berr, Bénédicte Stengel, Marie Metzger, J. F. Dartigues, Marc Froissart, Christophe Tzourio, and Catherine Helmer

Subjects
Male, medicine.medical_specialty, Population, Renal function, Comorbidity, Neuropsychological Tests, Cognition, Internal medicine, medicine, Dementia, Humans, Prospective Studies, Cognitive decline, Renal Insufficiency, Chronic, education, Aged, Aged, 80 and over, education.field_of_study, business.industry, Incidence, medicine.disease, Proteinuria, Relative risk, Cohort, Microalbuminuria, Female, Neurology (clinical), business, Kidney disease, Follow-Up Studies, Glomerular Filtration Rate
Abstract

To evaluate the longitudinal relationship between moderate chronic kidney disease (CKD), decline in kidney function, and microalbuminuria with subsequent cognitive decline and incident dementia.This study is based on a population-based cohort of 7,839 subjects over 65 years with 7 years of follow-up. Glomerular filtration rate was estimated (eGFR) using the CKD-EPI equation. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) and dementia was actively screened and diagnosed.At baseline, 12% of the participants had an eGFR60 mL/min/1.73 m(2). A total of 564 incident dementia cases were diagnosed during the follow-up. Low baseline eGFR values were not associated with an increased risk of incident dementia or cognitive decline over the 7-year follow-up, except a borderline significant association with dementia with vascular component. However, eGFR decline over the first 4-year period was associated with higher risk of dementia with vascular component (relative risk = 5.35 [1.76-16.3] in those with eGFR decline4 mL/min/1.73 m(2)/y compared with those4) and with higher cognitive decline on the MMSE (-0.12 points, p0.01 in those with eGFR4 mL/min/1.73 m(2)/y compared with those4) in the 3 subsequent years. Proteinuria tended to be associated with an increased risk of subsequent dementia with vascular component.Despite a large sample and a long follow-up, we found no increased risk of cognitive decline or dementia associated with low eGFR level. However, faster eGFR decline was associated with global cognitive decline and incident dementia with vascular component, suggesting that this association may be mediated by vascular mechanisms.

Published
2011

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