Author: "Marie Metzger" / Topic: nephrology - Searchworks@Jio Institute Digital Library Search Results

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1. Machine Learning-Based Urine Peptidome Analysis to Predict and Understand Mechanisms of Progression to Kidney Failure

Author: Ziad A. Massy, Oriane Lambert, Marie Metzger, Mohammed Sedki, Adeline Chaubet, Benjamin Breuil, Acil Jaafar, Ivan Tack, Thao Nguyen-Khoa, Melinda Alves, Justyna Siwy, Harald Mischak, Francis Verbeke, Griet Glorieux, Yves-Edouard Herpe, Joost P. Schanstra, Bénédicte Stengel, Julie Klein, Natalia ALENCAR DE PINHO, Carole AYAV, Dorothée CANNET, Christian COMBE, Jean-François DELEUZE, Denis FOUQUE, Luc FRIMAT, Yves-Edouard HERPE, Christian JACQUELINET, Maurice LAVILLE, Sophie LIABEUF, Ziad A. MASSY, Christophe PASCAL, Bruce ROBINSON, Roberto PECOITS-FILHO, Joost SCHANSTRA, Bénédicte STENGEL, Céline LANGE, Marie METZGER, and Elodie SPEYER
Subjects: Nephrology
Published: 2023
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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. MO496: Serum Urea Levels and Cardiovascular Disease in Patients With Chronic Kidney Disease

Author: Solene Laville, Aymeric Couturier, Oriane Lambert, Marie Metzger, Mansencal Nicolas, Christian Jacquelinet, Maurice Laville, Luc Frimat, Denis Fouque, Christian Combe, Bruce Robinson, Benedicte Stengel, Sophie Liabeuf, and Ziad Massy
Subjects: Transplantation, Nephrology
Abstract: BACKGROUND AND AIMS Elevated serum urea levels are common in moderate-to-advanced CKD. Several studies have shown that urea is a direct and indirect uremic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before kidney replacement therapy (KRT) in patients with CKD. METHOD CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 RESULTS Of the 2507 included patients {median [first quartile–third quartile (Q1–Q3)] age: 69 (61–77); mean (standard deviation) eGFR 33.5(11.6) mL/min/1.73 m²}, 54% had a history of cardiovascular disease. Over a median follow-up of 3.0 years [Q1–Q3, 2.2–3.1], 451 experienced their first atheromatous or nonatheromatous cardiovascular event (fatal or nonfatal), leading to an incidence rate (IR) [95% confidence interval (95% CI)] of 7.1 (6.4–7.7)/100 person-years (PYs) (Fig. 1). Over a median follow-up period of 4.8 (3.3–5.1) years, 407 patients died before KRT, leading to an IR of 4.0 (3.6–4.3)/100 PYs. After multiple adjustments for cardiovascular risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and nonatheromatous cardiovascular events than patients in T1 [HR (95% CI), 2.08 (1.50–2.88), Fig. 1]. A nonsignificant trend towards a higher risk was also noted for patients in T2 [1.28 (0.96–1.71)]. The adjusted HRs for death before KRT were 1.30 (0.96–1.75] and 1.73 (1.22–2.45) for patients in T2 and those in T3, respectively. CONCLUSION Beyond CV risk factors including eGFR, this hypothesis-generating study suggests that serum urea level is a predictor of cardiovascular outcomes in patients with moderate to advanced CKD. Further research is needed to confirm current findings and explore mechanisms.
Published: 2022
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4. 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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5. Urea levels and cardiovascular disease in patients with chronic kidney disease

Author: Solène M, Laville, Aymeric, Couturier, Oriane, Lambert, Marie, Metzger, Nicolas, Mansencal, Christian, Jacquelinet, Maurice, Laville, Luc, Frimat, Denis, Fouque, Christian, Combe, Bruce M, Robinson, Bénédicte, Stengel, Sophie, Liabeuf, Ziad A, Massy, CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, 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)-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, Service de cardiologie et maladies vasculaires [CHU Ambroise Paré], Agence de la biomédecine [Saint-Denis la Plaine], Université de Lyon, 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), 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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], INSERM U1026 (INSERM, U1026), Institut National de la Santé et de la Recherche Médicale (INSERM), Arbor Research Collaborative for Health, and LAVILLE, Solène
Subjects: Transplantation, Nephrology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: Background Elevated serum urea levels are common in moderate-to-advanced chronic kidney disease (CKD). Several studies have shown that urea is a direct and indirect uraemic toxin, especially with regard to cardiovascular disease. We sought to determine whether serum urea levels are associated with adverse cardiovascular events and death before renal replacement therapy (RRT) in patients with CKD. Methods CKD-REIN is a prospective cohort of CKD nephrology outpatients not receiving maintenance dialysis. The 2507 patients included in the analysis were divided into three groups according to the baseline serum urea level (T1 Findings Of the 2507 included patients {median [interquartile range (IQR)] age: 69 [61–77]; mean (standard deviation) estimated glomerular filtration rate (eGFR) 33.5 (11.6) mL/min/1.73 m²}, 54% had a history of cardiovascular disease. After multiple adjustments for CV risk factors (including eGFR), patients in T3 had a higher risk of atheromatous and non-atheromatous CV events than patient in T1 (n events = 451, HR [95% CI]: 1.93 [1.39; 2.69]). The adjusted HRs for death before RRT (n events = 407) were 1.31 [0.97; 1.76] and 1.73 [1.22; 2.45] for patients T2 and those in T3, respectively. Interpretation Our data suggested that urea is a predictor of CV outcomes beyond CV risk factors including eGFR.
Published: 2022
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6. Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

Author: Bénédicte Janbon, Sophie Caillard, Isabelle Jollet, Elisabeth Cassuto, Elodie Bailly, Bruno Hurault de Ligny, Michel Delahousse, Marc Hazzan, Anne Devys, Antoine Thierry, Pierre Merville, Sophie Girerd, Renaud Snanoudj, Dany Anglicheau, Vincent Vuiblet, Nassim Kamar, Kahina Amokrane, Philippe Grimbert, Eric Rondeau, Gabriel Choukroun, Alexandre Hertig, Marie Metzger, Jean-Luc Taupin, Yann Le Meur, Christophe Legendre, Emmanuel Morelon, Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Néphrologie et Transplantation [Strasbourg], Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, 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], Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement français du sang [Poitiers] (EFS), Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Département de Néphrologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie [Amiens], CHU Amiens-Picardie-hôpital Sud, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Transplantation rénale [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Etablissement français du sang [Angers], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Foch [Suresnes], Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France (Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de néphrologie et de transplantation rénale [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), 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)-CHU Necker - Enfants Malades [AP-HP], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, 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), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM)
Subjects: Adult, Graft Rejection, Male, 0301 basic medicine, Isoantigens, Allosensitization, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, 030232 urology & nephrology, kidney transplantation, Human leukocyte antigen, acute rejection, Epitope, 03 medical and health sciences, 0302 clinical medicine, Antigen, HLA-DQ Antigens, immunosuppression minimization, Humans, Transplantation, Homologous, Medicine, Everolimus, education, Kidney transplantation, education.field_of_study, biology, Drug Substitution, business.industry, Histocompatibility Testing, Patient Selection, Graft Survival, Immunosuppression, Middle Aged, epitopes, medicine.disease, HLA mismatching, 3. Good health, 030104 developmental biology, Nephrology, Immunology, Cyclosporine, antibody-mediated rejection, biology.protein, Female, Antibody, business, Immunosuppressive Agents, Follow-Up Studies
Abstract: International audience; Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ("epitope load") would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.
Published: 2019
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7. 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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8. Water intake and progression of chronic kidney disease: the CKD-REIN cohort study

Author: Christian Jacquelinet, Denis Fouque, Marie Metzger, Bénédicte Stengel, Lise Bankir, Christian Combe, Thomas Merkling, Maurice Laville, L. Frimat, Ziad A. Massy, Sandra Wagner, 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), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], 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_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), 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), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), 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), 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), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Agence de la biomédecine [Saint-Denis la Plaine], Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], The CKD-REIN study is funded by the Agence Nationale de la Recherche through the 2010 Cohortes-Investissements d’Avenir programme and by the 2010 national Programme Hospitalier de Recherche Clinique, CarMeN, laboratoire, Université Paris-Saclay, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP)
Subjects: Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Urology, Drinking, Renal function, Urine, water intake, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Risk Factors, urine osmolarity, Medicine, Humans, 030212 general & internal medicine, Renal Insufficiency, Chronic, kidney function, Aged, Osmole, Transplantation, Kidney, business.industry, Hazard ratio, Water, urine volume, medicine.disease, 3. Good health, kidney failure, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Nephrology, Urine osmolality, Disease Progression, Female, business, Kidney disease, Glomerular Filtration Rate
Abstract: Background Optimal daily water intake to prevent chronic kidney disease (CKD) progression is unknown. Taking the kidney’s urine-concentrating ability into account, we studied the relation of kidney outcomes in patients with CKD to total and plain water intake and urine volume. Methods Including 1265 CKD patients [median age 69 years; mean estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2] from the Chronic Kidney Disease–Renal Epidemiology and Information Network cohort (2013–19), we assessed fluid intake at baseline interviews, collected 24-h urine volumes and estimated urine osmolarity (eUosm). Using Cox and then linear mixed models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney failure and eGFR decline associated with hydration markers, adjusting for CKD progression risk factors and eUosm. Results Patients’ median daily intake was 2.0 L [interquartile range (IQR) 1.6–2.6] for total water and 1.5 L (1–1.7) for plain water, median urine volume was 1.9 L/24 h (IQR 1.6–2.4) and mean eUosm was 374 ± 104 mosm/L. Neither total water intake nor urine volume was associated with either kidney outcome. Kidney failure risk increased significantly with decreasing eUosm ˂292 mosm/L. Adjusted HRs (95% CIs) for kidney failure associated with plain water intake were 1.88 (1.02–3.47), 1.59 (1.06–2.38), 1.76 (0.95–3.24) and 1.55 (1.03–2.32) in patients drinking 2.0 L/day compared with those drinking 1.0–1.5 L/day. High plain water intake was also significantly associated with faster eGFR decline. Conclusions In patients with CKD, the relation between plain water intake and progression to kidney failure appears to be U-shaped. Both low and high intake may not be beneficial in CKD.
Published: 2021
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9. 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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10. 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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11. Valeurs de références du débit de filtration glomérulaire par sexe chez le sujet sain de 18 à 90 ans

Author: Bénédicte Stengel, Marc Froissart, Marie Metzger, Martin Flamant, Jean-Philippe Haymann, Pascal Houillier, Cédric Gauci, A.-L. Faucon, and A. Banchard
Subjects: Nephrology
Abstract: Introduction Les valeurs normales du debit de filtration glomerulaire (DFG) ne sont pas clairement etablies, notamment chez le sujet âge. Description L’objectif etait de decrire le declin physiologique du DFG selon l’âge et le sexe, chez le sujet sain, et d’evaluer les performances des equations d’estimation du DFG. Methodes Le DFG etait mesure par la clairance renale du 51Cr-EDTA chez 630 femmes et hommes en bonne sante, âges de 18–90 ans. Un modele GAMLSS a permis d’etablir les valeurs de reference du DFG. La relation entre DFG, âge et sexe a ete analysee a l’aide d’un modele lineaire par morceaux. Enfin, biais, precision et exactitude des equations CKD-EPI et FAS ont ete evaluees. Resultats Les participants (43 % d’hommes) avaient un DFG mesure (mDFG) moyen de 90,5 ± 15,9 mL/min/1,73 m2. Le 5e percentile restait superieur a 60 mL/min/1,73 m2 jusqu’a 80 ans chez les hommes, alors que ce seuil etait atteint par 5 % des femmes a 63 ans et par 25 % a 76 ans. Le mDFG diminuait physiologiquement avec l’âge a partir de 40 ans ( Fig. 1 ), plus rapidement chez la femme que chez l’homme, 0,83 ± 0,09 vs 0,67 ± 0,07 mL/min/1,73 m2 par an, p Globalement, le biais dans l’estimation du DFG etait significativement plus faible avec l’equation FAS qu’avec CKD-EPI, alors que la precision et l’exactitude ne differaient pas. Les performances des equations etaient similaires entre les deux sexes, mais CKD-EPI tendait a surestimer et FAS a sous-estimer le mDFG au-dessus de 65 ans. Conclusion Un declin physiologique plus rapide du DFG chez les femmes que chez les hommes pourrait expliquer le paradoxe associant une plus forte prevalence de la maladie renale chronique (MRC) a une plus faible incidence de la defaillance renale chez la femme. Les valeurs de reference sont a considerer pour le diagnostic de MRC et la prescription medicamenteuse, en particulier chez le sujet âge.
Published: 2021
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12. 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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13. 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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14. 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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15. 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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16. 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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17. 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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18. 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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19. Variations géographiques des pratiques de création des abords vasculaires pour hémodialyse en France

Author: Florian Bayer, B. Stengel, Cécile Couchoud, N. Alencar de Pinho, Raphaël Coscas, Marie Metzger, Ziad A. Massy, and E. Kolla
Subjects: Nephrology
Abstract: Introduction Les fistules et pontages arterioveineux sont preferables aux catheters pour l’hemodialyse chronique, mais restent insuffisamment utilises. Des comparaisons geographiques sur les pratiques de creation des voies d’abord peuvent nous informer sur leur potentiel de deploiement. Description Nous avons utilise les donnees du Registre REIN couple au systeme national des donnees de sante (SNDS) pour identifier les creations de fistule et de pontage avant le demarrage de l’hemodialyse chez 40 901 patients incidents de 2010 a 2015. Methodes Nous avons utilise des modeles lineaires generalises mixtes pour explorer les variations de prevalence entre departements, apres ajustement sur l’âge, le sexe, le statut diabetique, l’inscription sur liste d’attente de greffe renale, le demarrage en urgence, le statut juridique de l’etablissement, et la densite territoriale en nephrologues et chirurgiens vasculaires. Resultats Les patients avaient un âge median etait de 71 ans, 64 % etaient des hommes, 43 % avaient un diabete, et 33 % avaient demarre la dialyse en urgence. La moitie des patients avaient eu une creation de fistule (49 %) ou de pontage (1,7 %), respectivement 5 (IIQ : 2–12) et 3 (1–8) mois, en mediane, avant le demarrage de l’hemodialyse. La prevalence ajustee de creation de fistules variait d’un facteur 2 entre les departements francais, et celle de creation de pontages, d’un facteur 56. Les prevalences ajustees de fistules et de pontages sont inversement correlees, a −0,62. Conclusion Il existe des variations geographiques dans les pratiques de creation de voie d’abord en France peu expliquees par les caracteristiques des patients, les conditions du demarrage de la dialyse ou l’offre de soins en nephrologues et chirurgiens vasculaires. La creation de pontages semble plus souvent se substituer que s’additionner a celles des fistules.
Published: 2021
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20. 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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21. La parathormone est associée à une densité minérale osseuse basse, mais pas avec la perte osseuse longitudinale de la maladie rénale chronique

Author: Martin Flamant, Agnès Ostertag, Pascal Houillier, Martine Cohen-Solal, Marie Metzger, Pablo Ureña-Torres, and P.-E. Cailleaux
Subjects: Nephrology
Abstract: Introduction La maladie renale chronique (MRC) augmente le risque de fracture et la diminution de la densite minerale osseuse (DMO) en est un facteur predictif. Or, sa mesure n’est recommandee aux stades 3–5 de la MRC que si les resultats impactent les decisions therapeutiques. Une concentration elevee d’hormone parathyroidienne (PTH) est associee a des DMO basses et peut predire le risque fracturaire. On ignore si la PTH influence l’evolution longitudinale de la DMO chez ces patients. Description Nous avons analyse un sous-groupe de patients adultes participant a la cohorte prospective NephoTest, durant 4,3 ± 2,03 ans entre 2005 et 2013 pour lesquels les valeurs de DMO et de PTH etaient disponibles. Methodes Un modele lineaire mixte a evalue l’interaction entre PTH initiale et variation longitudinale de la DMO. Resultats Au total, 858 patients ont eu deux mesures de DMO (âge moyen 58,9 ± 15,2 ans, sex-ratio de 2/1). Deux pour cent etaient MRC stade 1, 18 % stade 2, 55 % stade 3, 20 % stade 4, 5 % stade 5. A l’inclusion, on retrouvait aux stades plus avances de MRC des concentrations plus elevees de PTH et des DMO plus basses (tous sites). Les DMO les plus basses etaient associees positivement aux concentrations les plus hautes de PTH, a un âge eleve, au sexe feminin et a un tabagisme actif. Apres 4,3 ans de suivi, avec un declin d’1,2 mL/min/an de debit de filtration glomerulaire (DFG), on n’a pas observe de lien entre la variation de DMO dans le temps ni avec le DFG ni avec la PTH initiale. Conclusion A l’inclusion dans l’etude, la PTH est inversement liee a la DMO. Le suivi de 4,3 ans ne retrouve pas de diminution significative de la DMO a tous les sites. La valeur initiale de PTH n’a pas d’impact sur l’infime variation de DMO chez les patients avec MRC aux stades 2–5.
Published: 2020
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22. 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

23. 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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24. 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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25. SP211RISK OF ACUTE KIDNEY INJURY, END-STAGE KIDNEY DISEASE AND MORTALITY ASSOCIATED WITH PROTON PUMP INHBITOR USE IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Author: Christian Jacquelinet, Marie Metzger, Luc Frimat, Christian Combe, Oriane Lambert, Solène M. Laville, Sophie Liabeuf, Bénédicte Stengel, Ziad A. Massy, Maurice Laville, Aghilès Hamroun, and Denis Fouque
Subjects: Transplantation, medicine.medical_specialty, Nephrology, business.industry, medicine, Acute kidney injury, Urology, In patient, End-stage kidney disease, medicine.disease, business, Kidney disease
Published: 2019
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26. Fasting Urinary Osmolality, CKD Progression, and Mortality: A Prospective Observational Study

Author: Jean-Philippe Haymann, Emmanuel Letavernier, Emmanuelle Vidal-Petiot, Martin Flamant, H. Fessi, Christian Jacquot, Jean-Jacques Boffa, Caroline du Halgouet, Pascal Houillier, Marion Vallet, Sandra Wagner, Gérard Maruani, Renaud de la Faille, François Vrtovsnik, Pierre Ronco, Eric Thervet, Eric Daugas, Marine Livrozet, Laurence Nicolet-Barousse, Marie Metzger, Bénédicte Stengel, Nahid Tabibzadeh, Alexandre Karras, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [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) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), French-Clinical Research Infrastructure Network [Lyon] (FCRIN INI-CRCT - Coordination Nationale Réseau FORCE), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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 Physiologie [Georges-Pompidou], 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)-Université Paris Descartes - Paris 5 (UPD5), 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), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, CHU Tenon [APHP], Service de Néphrologie et Dialyses [CHU Tenon], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-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], Service de Néphrologie et Hémodialyse [CHU 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Descartes - Paris 5 (UPD5)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, F-CRIN, INICRCT network, Paris, 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), Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and NephroTest Study Group: Marine Livrozet, Emmanuel Letavernier, Pierre Ronco, Hafedh Fessi, Emmanuelle Vidal-Petiot, Eric Daugas, Caroline du Halgouet, Renaud de La Faille, Gerard Maruani, Marion Vallet, Laurence Nicolet-Barousse, Alexandre Karras, Christian Jacquot
Subjects: Male, urine concentration ability, 030232 urology & nephrology, Urine osmolality, urologic and male genital diseases, tubular damage, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, Prospective Studies, prognostic factor, ComputingMilieux_MISCELLANEOUS, Fasting, Middle Aged, Prognosis, female genital diseases and pregnancy complications, 3. Good health, Survival Rate, Nephrology, Disease Progression, Biomarker (medicine), biomarker, Female, France, medicine.symptom, glomerular filtration rate (GFR), Cohort study, Glomerular Filtration Rate, medicine.medical_specialty, Urinary system, CKD progression, Urology, chronic kidney disease (CKD), 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Risk factor, Renal Insufficiency, Chronic, business.industry, Osmolar Concentration, medicine.disease, measured GFR (mGFR), Decreased glomerular filtration rate, end-stage renal disease (ESRD), Albuminuria, GFR decline, business, Biomarkers, Kidney disease
Abstract: International audience; Rationale & objective: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD).Study design: Prospective longitudinal cohort study.Setting & participants: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study.Predictor: Fasting urinary osmolality measured using delta cryoscopy.Outcomes: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance.Analytical approach: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR.Results: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile.Limitations: Fasting was self-reported.Conclusions: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.
Published: 2019
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27. Extracellular fluid volume is associated with incident end-stage kidney disease and mortality in patients with chronic kidney disease

Author: Anne-Laure Faucon, Martin Flamant, Marie Metzger, Jean-Jacques Boffa, Jean-Philippe Haymann, Pascal Houillier, Eric Thervet, François Vrtovsnik, Bénédicte Stengel, Guillaume Geri, Emmanuelle Vidal-Petiot, Eric Daugas, Nahid Tabibzadeh, Alexandre Karras, Stéphane Roueff, Marie Courbebaisse, Caroline Prot-Bertoye, Jean-Philippe Bertocchio, Gérard Maruani, Pierre Ronco, Hafedh Fessi, Eric Rondeau, Marine Livrozet, Emmanuel Letavernier, Pablo Urena-Torres, Centre Hospitalier Sud Francilien, CH Evry-Corbeil, Service de Réanimation polyvalente, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Physiologie [Georges-Pompidou], 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)-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), 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), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-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) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris Descartes - Paris 5 (UPD5)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (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)-Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-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), CHU Tenon [APHP], and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, 030232 urology & nephrology, Urology, Water-Electrolyte Imbalance, Renal function, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Risk Factors, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Extracellular fluid, Medicine, Humans, Prospective Studies, Risk factor, Renal Insufficiency, Chronic, ComputingMilieux_MISCELLANEOUS, Aged, Body surface area, business.industry, Incidence, Hazard ratio, Extracellular Fluid, Middle Aged, medicine.disease, Prognosis, Confidence interval, 3. Good health, 030104 developmental biology, Nephrology, Cohort, Disease Progression, Kidney Failure, Chronic, Female, business, Kidney disease, Glomerular Filtration Rate
Abstract: Volume overload has been shown to be an independent risk factor for mortality in patients receiving chronic dialysis, but data in non-dialysis patients are scarce. Therefore we evaluated the prognostic value of extracellular fluid (ECF) volume for chronic kidney disease (CKD) progression and mortality in a prospective hospital-based cohort with CKD stage 1-4 (NephroTest Study). ECF (scaled to body surface area) and the measured glomerular filtration rate (mGFR) were determined using the distribution volume and clearance of 51Cr-EDTA, respectively. Cause-specific Cox and linear mixed-effect regression models were used to analyze the association of ECF with end-stage kidney disease (ESKD) and mortality, and with mGFR decline, respectively. The 1593 patients were mean age 58.8 years, 67% were men, mean mGFR of 43.6 mL/min/1.73m2 and mean ECF 15.1 L/1.73m2. After a median follow-up of 5.3 years, ESKD occurred in 324 patients and 185 patients died before ESKD. In multivariable analysis, ECF was significantly associated with the risk of ESKD (hazard ratio per 1L/1.73m2 increase: 1.14; 95% confidence interval [1.07; 1.21]) and with a faster GFR decline (adjusted mean difference in mGFR slope per 1L/1.73m2 increase -0.14 [-0.23; -0.05] mL/min/year). The relationship of ECF with mortality was non-linear and not significant (per 1L/1.73m2 increase 0.92, [0.73; 1.16]), below 15L/1.73m2, but significant (1.28; [1.14-1.45]) above 15L/1.73m2. Thus, in this large cohort of carefully phenotyped patients with CKD, ECF was an independent risk factor of CKD progression and mortality. Hence, close monitoring and treatment of fluid overload are important for the clinical management of patients with non-dialysis CKD.
Published: 2019
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28. 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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29. Effects of the dialysate calcium concentrations and mineral bone disease treatments on mortality in The French Renal Epidemiology and Information Network (REIN) registry

Author: Marie Metzger, Cécile Couchoud, Lucile Mercadal, Christian Jacquelinet, Gabriel Choukroun, Oriane Lambert, 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), Agence de la biomédecine [Saint-Denis la Plaine], Nephrology, Dialysis & Transplantation Department [Amiens], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de néphrologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), The study was funded by the Agence de la Biomédecine in 2016 and by the Société Francophone Néphrologie Dialyse et Transplantation in 2017 (Baxter grant). Author LM received fees for a medical speech about the results of the study at an AMGEN conference., Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [CHU Pitié-Salpêtrière], 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), 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), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Bodescot, Myriam
Subjects: Male, Cinacalcet, Physiology, medicine.medical_treatment, 030232 urology & nephrology, Organic chemistry, Sevelamer, 030204 cardiovascular system & hematology, Vascular Medicine, Biochemistry, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 0302 clinical medicine, Medicine and Health Sciences, Renal Transplantation, Coronary Heart Disease, Longitudinal Studies, Registries, Vitamin D, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Multidisciplinary, Hazard ratio, Calcinosis, Vitamins, Middle Aged, 3. Good health, Physical sciences, Chemistry, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Nephrology, Medicine, Female, France, Hemodialysis, Research Article, Chemical Elements, medicine.drug, medicine.medical_specialty, Death Rates, Bone and Mineral Metabolism, Science, Cardiology, Urology, chemistry.chemical_element, Surgical and Invasive Medical Procedures, Calcium, Bone and Bones, Urinary System Procedures, Calcification, Chemical compounds, 03 medical and health sciences, Population Metrics, Lanthanum, Renal Dialysis, Medical Dialysis, Organic compounds, medicine, Humans, Renal Insufficiency, Chronic, Dialysis, Aged, Proportional Hazards Models, Calcium metabolism, Transplantation, Population Biology, business.industry, Biology and Life Sciences, Organ Transplantation, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Hemodialysis Solutions, Metabolism, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Blood Vessels, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Physiological Processes, business
Abstract: International audience; Background: In patients on hemodialysis (HD), the various chemical elements in the dialysate may influence survival rates. In particular, calcium modifies mineral and bone metabolism and the vascular calcification rate. We studied the influence of the dialysate calcium concentration and the treatments prescribed for mineral bone disease (MBD) on survival.Methods: All patients in REIN having initiated HD from 2010 to 2013 were classified according to their exposure to the different dialysate calcium concentrations in their dialysis unit. Data on the individual patients' treatments for MBD were extracted from the French national health database. Cox proportional hazard models were used to estimate mortality hazard ratios (HR) associated with time-dependent exposure to dialysate calcium concentrations and MBD therapies, adjusted for comorbidities, laboratory and technical data.Results: Dialysate calcium concentration of 1.5 mmol/L was used by 81% of the dialysis centers in 2010 and in 83% in 2014. Most centers were using several formulas in up to 78% for 3 formulas in 2010 to 86% in 2014. In full adjusted Cox survival analyses, the percentage of calcium >1.5 mmol/L and
Published: 2020
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30. SAT-095 URINE OSMOLARITY AND CHRONIC KIDNEY DISEASE PROGRESSION IN THE CKD-REIN COHORT

Author: Christian Jacquelinet, L. Frimat, Lise Bankir, S. Bénédicte, Denis Fouque, Christian Combe, Ziad A. Massy, Thomas Merkling, Marie Metzger, Maurice Laville, and Sandra Wagner
Subjects: medicine.medical_specialty, Nephrology, business.industry, Cohort, Urology, medicine, Urine osmolality, medicine.disease, business, Kidney disease
Published: 2020
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31. 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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32. Impact de l’évolution du volume extracellulaire sur le risque de mortalité et le risque de progression vers l’insuffisance rénale chronique terminale

Author: Jean-Philippe Haymann, A.-L. Faucon, Karen Leffondré, Guillaume Geri, Emmanuelle Vidal-Petiot, Jean-Jacques Boffa, Eric Thervet, François Vrtovsnik, Marie Metzger, and Pascal Houillier
Subjects: Nephrology
Abstract: Introduction Aucune etude n’a evalue l’impact de l’evolution du volume extracellulaire (VEC) sur la survenue d’une insuffisance renale chronique terminale (IRCT) et sur la mortalite, au cours de la maladie renale chronique (MRC). Description claire et complete de l’experience Dans une cohorte prospective, 1588 patients ayant une MRC de stades 1 a 4 ont ete inclus. A chaque visite, le VEC et le debit de filtration glomerulaire (DFG) etaient respectivement obtenus par la mesure du volume de distribution et la clairance du 51Cr-EDTA. Methodes Des modeles conjoints, permettant l’analyse simultanee des donnees repetees de VEC et des donnees de survie (avec prise en compte des risques competitifs) ont ete utilises. Les criteres de jugements etaient la survenue d’une IRCT et la mortalite toutes causes. Resultats obtenus ou attendus A l’inclusion, les patients (âge 58,7 ± 15,1 ans, 67 % d’hommes) avaient un DFG moyen de 44 ± 19 mL/min/1,73m2, et un VEC de 16,1 ± 3,6 L. La prescription de diuretique passait de 35,0 a 57,4 % du stade 1 a 4. L’excretion urinaire de sodium etait en moyenne de 155 mmol/24 h. Apres un suivi median de 5,3 [IQR : 3,0 ;7,4] ans (nombre median de mesures de 2 [1 ;4] par patient), le VEC augmentait en moyenne de 117 mL/an IC95 % [90 ; 144]. 329 (20,4 %) patients ont developpe une IRCt et 187 (11,6 %) sont decedes avant la survenue d’une IRCt. La valeur de courante de VEC etait associee au risque instantane de survenue d’une IRCt (HR ajuste pour l’augmentation d’1L de VEC : 1,12 IC95 % [1,06 ; 1,18], p Conclusion Nos resultats suggerent que le VEC est un facteur independant d’IRCT et de mortalite, soulignant l’importance de la surveillance de ce parametre et la necessite d’adapter les mesures dietetiques et le traitement diuretique chez les patients suivis pour une MRC.
Published: 2019
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33. SUN-256 Pure water intake and chronic kidney disease progression to end-stage

Author: Bénédicte Stengel, Marie Metzger, Lise Bankir, Ziad A. Massy, and Sandra Wagner
Subjects: medicine.medical_specialty, Nephrology, business.industry, Internal medicine, medicine, Water intake, Stage (cooking), business, medicine.disease, Gastroenterology, Kidney disease
Published: 2019
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34. 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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35. 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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36. Urinary creatinine excretion, measured glomerular filtration rate and CKD outcomes

Author: Jean-Philippe Haymann, Pascal Houillier, François Vrtovsnik, Bénédicte Stengel, Eric Thervet, Marie Metzger, Elena Tynkevich, Marc Froissart, Martin Flamant, and Jean-Jacques Boffa
Subjects: Male, medicine.medical_specialty, Urinary system, Urology, Renal function, urologic and male genital diseases, End stage renal disease, chemistry.chemical_compound, Risk Factors, Humans, Medicine, Prospective Studies, Renal Insufficiency, Chronic, Wasting, Aged, Proportional Hazards Models, Transplantation, Creatinine, business.industry, Proportional hazards model, Hazard ratio, Middle Aged, Prognosis, medicine.disease, female genital diseases and pregnancy complications, Survival Rate, Proteinuria, chemistry, Nephrology, Disease Progression, Female, medicine.symptom, business, Biomarkers, Glomerular Filtration Rate, Kidney disease
Abstract: Muscle wasting predicts mortality in patients with end-stage renal disease (ESRD), but its role in the progression of chronic kidney disease (CKD) is uncertain. We studied CKD outcomes associated with low muscle mass, assessed by urinary creatinine excretion (UCr).The NephroTest cohort included 1429 patients with CKD stages 1-4 and both measured glomerular filtration rate (mGFR) (by (51)Cr-EDTA) and estimated glomerular filtration rate (eGFR) (by CKD-Epidemiology Collaboration equation). We used cause-specific Cox models to estimate hazard ratios (HRs) for the competing risks of ESRD and death associated with gender-specific UCr quartiles.UCr was 13.6 ± 3.2 mmol/24 h (0.17 ± 0.05 mmol/kg/24 h) in men and 9.2 ± 2.1 (0.14 ± 0.05) in women. It was positively associated with mGFR, but not with eGFR. Over a median follow-up of 3.6 (2.1-5.8) years, 229 patients developed ESRD and 113 patients died before ESRD. Compared with patients in the highest UCr quartile, those in the lowest quartile had a higher crude HR (95% confidence interval) for pre-ESRD death: 4.3 (2.4-7.7), which was weakened, but remained statistically significant, independent of demographics, mGFR and several other factors: 2.1 (1.04-4.3). Their crude ESRD risk was not higher: HR: 0.95 (0.65-1.4), and even tended to be lower after adjusting for mGFR and log-proteinuria: HR: 0.70 (0.45-1.1). Adjustment for eGFR instead of mGFR reversed this relationship: HR: 1.7 (1.1-2.7).In early stage CKD, low UCr is associated with higher risk for mortality, but not for ESRD. Using creatinine-based equation to adjust for GFR may bias the relationship of UCr with ESRD risk.
Published: 2015
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37. Correction to: Association of plasma potassium with mortality and end-stage kidney disease in patients with chronic kidney disease under nephrologist care - The NephroTest study

Author: Sandra Wagner, Marie Metzger, Martin Flamant, Pascal Houillier, Jean-Philippe Haymann, François Vrtovsnik, Eric Thervet, Jean-Jacques Boffa, Ziad A. Massy, Bénédicte Stengel, Patrick Rossignol, and for the NephroTest Study group
Subjects: Plasma potassium, Cardiovascular mortality, Nephrology, Chronic kidney disease, End-stage kidney disease, Hyperkalemia, Hypokalemia, Mortality, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, Research Article
Abstract: Background Low and high blood potassium levels are common and were both associated with poor outcomes in patients with chronic kidney disease (CKD). Whether such relationships may be altered in CKD patients receiving optimized nephrologist care is unknown. Methods NephroTest is a hospital-based prospective cohort study that enrolled 2078 nondialysis patients (mean age: 59 ± 15 years, 66% men) in CKD stages 1 to 5 who underwent repeated extensive renal tests including plasma potassium (PK) and glomerular filtration rate (GFR) measured (mGFR) by 51Cr-EDTA renal clearance. Test reports included a reminder of recommended targets for each abnormal value to guide treatment adjustment. Main outcomes were cardiovascular (CV) and all-cause mortality before end-stage kidney disease (ESKD), and ESKD. Results At baseline, median mGFR was 38.4 mL/min/1.73m2; prevalence of low PK (5 mmol/L) 6.4%; 74.4% of patients used angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). After excluding 137 patients with baseline GFR
Published: 2017
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38. 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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39. Évaluation de la prévalence des prescriptions médicamenteuses non adaptées à la fonction rénale selon la prise en compte de la surface corporelle pour estimer le DFG

Author: Sophie Liabeuf, Ziad A. Massy, B. Stengel, L. Frimat, Solène M. Laville, Denis Fouque, Marie Metzger, Christian Jacquelinet, C. Combe, and Maurice Laville
Subjects: Nephrology
Abstract: Introduction Adapter les doses de medicaments au debit de filtration glomerulaire estime (DFGe) par equation est difficile, notamment chez les personnes obeses. Nous avons evalue la prevalence de prescriptions non adaptees chez des patients atteints de maladie renale chronique (MRC), en estimant le DFG par l’equation CKD-EPI, indexee ou non a la surface corporelle (SC). Patients/Materiels et methodes Dans une cohorte incluant 3033 patients suivis en nephrologie pour une MRC avec un DFGe entre 15 et 60 mL/min/1,73 m2, nous avons examine les doses journalieres de principe actif prescrites dans les 3 mois precedant l’inclusion dans l’etude. Une prescription non adaptee a la fonction renale (fondee sur les recommandations des resumes des caracteristiques des produits) a ete definie comme la prescription declaree d’un medicament contre-indique ou a une dose trop elevee pour le DFGe du patient. Observation/Resultats L’âge median [ecart interquartile] des patients etait de 69 [61–76] ans ; 66 % etaient des hommes, 43 % avaient un diabete et 36 %, un indice de masse corporelle ≥ 30 kg/m2. La SC moyenne etait de 1,90 ± 0,22 m2. Le DFGe moyen etait respectivement de 33 mL/min/1,73 m2 et 36 mL/min, selon que l’equation etait indexee ou non a la SC. Le nombre median de medicaments prescrits etait de 8 [5–10] par jour. La proportion de patients avec au moins une prescription non adaptee au DFGe etait de 52 % avec, et de 47 % sans indexation a la SC. Les hypouricemiants, les antidiabetiques et les medicaments a visee cardiovasculaire etaient les principales classes de medicaments incriminees. Les patients diabetiques avaient avec une SC moyenne de 1,97 ± 0,21 m2 et un DFGe moyen, respectivement, de 33 mL/min/1,73 m2 et 37 mL/min avec et sans indexation a la SC. En consequence, chez les 273 patients sous metformine (seule ou en association), la prescription etait apparemment contre-indiquee chez 53 patients (19 %) avec un DFGe indexe a la SC Discussion/Conclusion La prevalence globale des prescriptions non adaptees a la fonction renale touche pres d’un patient sur deux avec une MRC moderee ou avancee. La prise en compte de la SC pour estimer le DFG induit des variations dans l’evaluation de cette prevalence qui sont d’autant plus importantes que la SC moyenne s’ecarte de la valeur standard de 1,73 m2. Il reste cependant a determiner si la desindexation de l’equation CKD-EPI modifie l’estimation de l’effet de ces prescriptions apparemment non adaptees sur les risques d’evenements iatrogenes, d’hospitalisations et de mortalite.
Published: 2018
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40. Hyperuricémie et progression de la maladie rénale chronique : données longitudinales de la cohorte CKD-REIN

Author: Karen Leffondré, Ziad A. Massy, Christian Combe, Céline Lange, Mathilde Prezelin-Reydit, Marie Metzger, Jérôme Harambat, Bénédicte Stengel, and Oriane Lambert
Subjects: Nephrology
Abstract: Introduction L’identification de facteurs de progression de la maladie renale chronique (MRC) est primordiale. L’association entre hyperuricemie et progression de la MRC n’est pas clairement etablie, notamment en Europe et n’a pas, a notre connaissance, ete etudiee a l’aide de donnees repetees dans le temps. Methodes A partir de la cohorte CKD-REIN, nous avons inclus les individus presentant une MRC de stade 3 a 5 non dialyses et ayant au moins une mesure d’uricemie et de creatininemie a + - 6 mois de leur inclusion. Toutes les valeurs d’uricemie ont ete prises en compte, de l’inclusion jusqu’a la fin du suivi ou la survenue de l’evenement d’interet defini par la premiere occurrence entre debut d’un traitement de suppleance (DTS) ou deces. Nous avons utilise un modele conjoint, combinant un modele de survie, permettant de modeliser la survie des individus en fonction de leur trajectoire d’uricemie modelisee par un modele lineaire mixte, ajuste ou non sur l’âge, le sexe, l’ethnie, la presence d’un syndrome metabolique, les antecedents cardiovasculaires, la maladie renale initiale, la proteinurie et le debit de filtration glomerulaire (DFG) initial. Resultats obtenus ou attendus Dans notre analyse, 2781 individus (65,5 % d’hommes, âge median 69 ans), ont ete inclus puis suivis pendant 3,2 ans. A l’inclusion, le DFG median (CKD-EPI) etait de 31,8 ml/min/1,73m2 et l’uricemie mediane a 425,0 μmol/l. Apres ajustement, le risque instantane de deces ou de DTS etait significativement augmente de 11 % pour une augmentation de 100 μmol/l de la valeur courante d’uricemie, en tout temps au cours du suivi (HR 1,11, IC 95 % 1,03–1,20). Conclusion Le niveau d’uricemie courant est associe a une augmentation du risque instantane de deces ou de DTS dans une population europeenne presentant une MRC de stade 3 a 5.
Published: 2019
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41. 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. O'Reilly, David Hadley, Hermann Brenner, Paolo Gasparini, Nanette R. Lee, Bamidele O. Tayo, Robert Clarke, Henri Wallaschofski, Marketa Sjögren, Abbas Dehghan, Melanie Waldenberger, Neil Risch, Vasyl Pihur, Jessica D. Faul, François Cambien, Christian Fuchsberger, Nicholas G. Martin, John C. Chambers, Zouhair Aherrahrou, Karl J. Lackner, Leif Groop, Matthias Olden, Wiek H. van Gilst, Mathias Gorski, Yvonne T. van der Schouw, Patrick Diemert, Christoph Bickel, Yik Ying Teo, Giorgio Pistis, Ruth J. F. Loos, Gudrun Veldre, Thorsten Reffelmann, Lude Franke, Karen L. Mohlke, Stefan Blankenberg, Massimo Mangino, Ian N. M. Day, Atsushi Takahashi, Alan B. Zonderman, Hua Tang, Reijo Laaksonen, Holly Kramer, Gary C. Curhan, Adrienne Tin, Talin Haritunians, Loic Yengo, Philip Howard, Arnika Kathleen Wagner, Anna Maria Corsi, Yen Pei C. Chang, Karin Halina Greiser, Jeanette Erdmann, Solveig Gretarsdottir, Sanjay Kinra, Alex Parker, Belen Ponte, Marina Ciullo, Michael Preuss, Tin Aung, Nicholas L. Smith, Michiaki Kubo, Richard N. Bergman, Alan S. Go, Patricia P. Chang, Gudmundur Thorgeirsson, Christa Meisinger, Gonçalo R. Abecasis, Maria Blettner, Jaana Laitinen, Daniel Taliun, Carlos Iribarren, Paavo Zitting, Thomas Lumley, Andreas Meinitzer, Wayne D. Rosamond, Daehee Kang, Johanne Tremblay, Stephan B. Felix, Colin A. McKenzie, Yuan-Tsong Chen, Lyudmyla Kedenko, Mladen Boban, Fadi J. Charchar, Adebowale Adeyemo, Brendan M. Buckley, Jennifer A. Smith, Reinhold Schmidt, Jaspal S. Kooner, Gavin Lucas, Paul Elliott, Dorairajan Prabhakaran, Tune H. Pers, Tunde Salako, Terrence Forrester, Paul Burton, Jeffrey R. Gulcher, Kelly A. Volcik, Richard M. Myers, Andreas Tomaschitz, H.-Erich Wichmann, Jie Yao, Giuseppe Matullo, Carsten A. Böger, Henry Völzke, Daniela Ruggiero, Federico Murgia, Yoshikuni Kita, Augustine Kong, Giovanni Gambaro, Cinzia Sala, Peter P. Pramstaller, James Scott, Maris Laan, Laura J. Scott, Alistair S. Hall, Sanaz Sedaghat, James F. Wilson, Joanne M. Murabito, Yi-An Ko, Honghuang Lin, Mark Seielstad, Leena Peltonen, Sven Bergmann, Thomas Meitinger, Matthias Nauck, María Soler Artigas, Thomas Illig, Nanette I. Steinle, Samer S. Najjar, Christina Loley, Debbie A Lawlor, Steven C. Hunt, Yali Li, Weihua Zhang, Jie Jin Wang, Daniele Cusi, Marco Orrù, Stephen P. Fortmann, Melissa Garcia, Barry I. Freedman, Joseph M. Lindsay, Juan P. Casas, Tomohiro Katsuya, Grant W. Montgomery, Hubert Scharnagl, Khanh-Dung H. Nguyen, Steven M. Schwartz, Afshin Parsa, Elizabeth G. Holliday, Murielle Bochud, Kiran Musunuru, Bruno H. Stricker, Lori L. Bonnycastle, Ilja M. Nolte, Timothy M. Frayling, Stefan Enroth, Michiel L. Bots, Mark J. Caulfield, Laura Portas, Vincent Chouraki, Carl D. Langefeld, Eran Halperin, Shufeng Chen, Philippa J. Talmud, Terho Lehtimäki, Steve E. Humphries, Gudmar Thorleifsson, Anika Grosshennig, Norbert Watzinger, Fumihiko Takeuchi, Pim van der Harst, Takayoshi Ohkubo, Nabila Bouatia-Naji, Erwin P. Bottinger, Roberto Elosua, Andrew Wong, Vladan Mijatovic, Maija K. Garnaas, Robert Zweiker, Joel N. Hirschhorn, Winfried März, Nilesh J. Samani, Inke R. König, Frank B. Hu, Marcus E. Kleber, Francis S. Collins, Elena Rochtchina, Ewa Zukowska-Szczechowska, Yong Li, Ayse Demirkan, Gina Hilton, G. Ehret, Thomas H. Mosley, Markus Perola, Alexandre F.R. Stewart, Josef Coresh, Olli T. Raitakari, Feng Zhang, Mark Lathrop, Michael Marmot, Yanbin Dong, Christopher J. O'Donnell, Kristin D. Marciante, Asif Rasheed, Mary F. Feitosa, Mary Susan Burnett, Rory Collins, J. Wouter Jukema, Nele Friedrich, Aida Karina Dieffenbach, Ying Wu, Yoon Shin Cho, Aaron Isaacs, Haidong Zhu, Marie Metzger, Myriam Alexander, Tanja B. Grammer, Tatiana Kuznetsova, Dabeeru C. Rao, Jayashri Aragam, Augusto D. Pichard, Jaakko Tuomilehto, Louise V. Wain, Elizabeth J. Atkinson, Tim D. Spector, Reedik Mägi, Tiit Nikopensius, Kenneth M. Kent, Guangju Zhai, Andrew D. Johnson, Menno Pruijm, David P. Strachan, Martin D. 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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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42. 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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43. 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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44. 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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45. Hemodiafiltration Versus Hemodialysis and Survival in Patients With ESRD: The French Renal Epidemiology and Information Network (REIN) Registry

Author: Christian Jacquelinet, François de Cornelissen, Clémence Béchade, Cécile Vigneau, Bénédicte Stengel, Stéphane Edet, Tilman B. Drüeke, Lucile Mercadal, Jeanna-Eve Franck, Pablo Urena Torres, Marie Metzger, 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), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de néphrologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Direction Médicale et Scientifique, Agence de la biomédecine [Saint-Denis la Plaine], R13180LL, Biomedicine Agency, 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 Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]
Subjects: Male, medicine.medical_specialty, Pediatrics, Survival, Epidemiology, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Hemodiafiltration, 030204 cardiovascular system & hematology, hemodiafiltration (HDF), law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, cardiovascular mortality, Renal Dialysis, treatment modality, Medicine, Humans, Prospective Studies, Registries, Mortality, Prospective cohort study, Survival rate, Dialysis, Aged, Hemodialysis (HD), Aged, 80 and over, Information Services, integumentary system, business.industry, Proportional hazards model, Middle Aged, 3. Good health, Survival Rate, Nephrology, end-stage renal disease (ESRD), registry-based study, Kidney Failure, Chronic, Observational study, Female, Hemodialysis, France, business
Abstract: International audience; Background Recent randomized trials report that mortality is lower with high-convection-volume hemodiafiltration (HDF) than with hemodialysis (HD). Study Design We used data from the French national Renal Epidemiology and Information Network (REIN) registry to investigate trends in HDF use and its relationship with mortality in the total population of incident dialysis patients. Setting & Participants The study included those who initiated HD therapy from January 1, 2008, through December 31, 2011, and were dialyzed for more than 3 months; follow-up extended to the end of 2012. Factor HDF use at the patient and facility level. Outcomes All-cause and cardiovascular mortality, using Cox models to estimate HRs of HDF as time-dependent covariate at the patient level, with age as time scale and fully adjusted for comorbid conditions and laboratory data at baseline, catheter use, and facility type as time-dependent covariates. Analyses completed by Cox models for HRs of the facility-level exposure to HDF updated yearly. Results Of 28,407 HD patients, 5,526 used HDF for a median of 1.2 (IQR, 0.9-1.9) years; 2,254 of them used HDF exclusively. HRs for all-cause and cardiovascular mortality associated with HDF use were 0.84 (95% CI, 0.77-0.91) and 0.73 (95% CI, 0.61-0.88), respectively. In patients treated exclusively with HDF, these HRs were 0.77 (95% CI, 0.67-0.87) and 0.66 (95% CI, 0.50-0.86). At the facility level, increasing the percentage of patients using HDF from 0% to 100% was associated with HRs for all-cause and cardiovascular mortality of 0.87 (95% CI, 0.77-0.99) and 0.72 (95% CI, 0.54-0.96), respectively. Limitations Observational study. Conclusions Whether analyzed as a patient- or facility-level predictor, HDF treatment was associated with better survival
Published: 2015
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46. 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

47. Déterminants de l’hypertension artérielle au cours de la maladie rénale chronique : résultats de la cohorte Nephrotest

Author: Jean-Philippe Haymann, Eric Thervet, Pascal Houillier, Martin Flamant, Emmanuelle Vidal-Petiot, Marie Metzger, Bénédicte Stengel, Jean-Jacques Boffa, and François Vrtovsnik
Subjects: Nephrology
Abstract: Introduction L’hypertension arterielle (HTA) est tres frequente au cours de la maladie renale chronique (MRC). Le but de l’etude etait de decrire les determinants du controle tensionnel et de l’HTA resistante dans une population de patients atteints de MRC. Patients et methodes Il s’agit d’une etude transversale de la cohorte tricentrique Nephrotest, a partir de la visite d’inclusion (n = 2084). Les patients, atteints de MRC stades 1 a 5, ont tous beneficie d’une mesure du debit de filtration glomerulaire (DFG) par clairance du 51CrEDTA, et d’une mesure du volume extracellulaire (VEC) a partir du volume de distribution du traceur. L’HTA etait definie par une pression arterielle (moyenne de 3 mesures cliniques) superieure a 140/90 mmHg ou la prise d’un traitement antihypertenseur. Une HTA resistante etait definie par une pression arterielle non controlee (> 140/90) malgre 3 traitements incluant un diuretique, ou par la prise d’au moins 4 traitements dont un diuretique, quel que soit le niveau tensionnel. Resultats Des donnees completes etaient disponibles chez 1938 patients (67 % d’homme) ; l’âge moyen etait de 59 ± 15 ans, le DFG moyen de 41,4 ± 19,6 mL/min/1,73 m2, et la prevalence de l’HTA de 94 %. Chez les 1821 patients hypertendus, les prevalences de l’HTA non controlee et resistante etaient respectivement de 42,2 et 31,7 %. En analyse multivariee, l’âge, l’albuminurie et le VEC plus eleves, une nephropathie diabetique et l’absence d’anti-aldosterone (mais pas le diabete, l’origine africaine, le DFG, ni le BMI) etaient significativement associes au non-controle tensionnel. L’âge, l’albuminurie, le VEC, le BMI et l’uricemie plus eleves, un DFG plus bas, un diabete, une nephropathie diabetique, une origine africaine etaient significativement associes a l’HTA resistante. Discussion Cette large cohorte de patients ayant beneficie d’explorations fonctionnelles renales dont une mesure du DFG et du VEC a permis une etude physiopathologique des determinants du controle et de la severite de l’HTA au cours de la MRC. Conclusion L’augmentation du VEC est un determinant independant, de l’HTA resistante et de l’HTA non controlee au cours de la MRC. L’insuffisance renale est associee a la severite de l’hypertension mais n’est pas un facteur de non-controle, moyennant un traitement approprie et une depletion hydro-sodee suffisante.
Published: 2016
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48. Osmolalité urinaire à jeun : un marqueur de progression de la maladie rénale chronique

Author: Martin Flamant, Bénédicte Stengel, Pascal Houillier, Jean-Philippe Haymann, Emmanuel Letavernier, François Vrtovsnik, Eric Thervet, Jean-Jacques Boffa, N. Tabibzadeh, and Marie Metzger
Subjects: Nephrology
Abstract: Introduction Les troubles de concentration des urines ont ete decrits dans des modeles experimentaux d’insuffisance renale. Ils ont ete peu etudies chez l’homme au cours de la maladie renale chronique (MRC). Patients et methodes Cette etude prospective longitudinale de la cohorte Nephrotest a inclus 2084 patients ayant une MRC (stades I a V) avec une mesure du debit de filtration glomerulaire (DFGm) par la clairance renale du 51Cr-EDTA, ainsi qu’un bilan complet comprenant une mesure de l’osmolalite urinaire a jeun (Uosm). Le devenir de 1796 patients a ete analyse apres exclusion des perdus de vue, des MRC stade V et des patients n’ayant pas eu de mesure d’Uosm et de la natremie a jeun. Resultats La mediane de suivi etait de 5,2 ans [2,9–7,5]. Une baisse d’osmolalite urinaire a jeun etait associee a un risque significativement augmente d’insuffisance renale terminale necessitant un traitement de suppleance (IRCT). La relation persiste apres stratification sur le niveau de fonction renale et ajustement sur les donnees sociodemographiques, les facteurs de risques connus d’IRCT (comprenant le rapport albumine/creatinine urinaires [ACR], le type de nephropathie et le diabete) et la natremie. Le risque relatif d’evolution vers l’IRCT pour le tertile le plus bas d’Uosm ( 557 mosm/kgH2O chez l’homme, 522 mosm/kgH2O chez la femme) etait de 2,24 [1,43–3,50]. Uosm n’etait pas associe avec la mortalite. En analyse multivariee, Uosm etait correlee au DFGm (b = 0,36 p Discussion Les troubles de concentration des urines sont le temoin de l’atteinte medullaire renale. Conclusion Uosm est un facteur pronostique d’une evolution vers l’IRCT, independant de parametres glomerulaires tels le DFG et l’albuminurie.
Published: 2016
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49. 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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50. SO001RELATIVE BURDEN OF ATHEROMATOUS AND NON-ATHEROMATOUS CARDIOVASCULAR DISEASE IN CKD PATIENTS: IMPACT OF AGE

Author: Marie Metzger, Bruce G. Robinson, Ziad A. Massy, Maurice Laville, Christian Jacquelinet, Cédric Villain, Christian Combe, Bénédicte Stengel, Denis Fouque, and Luc Frimat
Subjects: Transplantation, medicine.medical_specialty, Nephrology, business.industry, Internal medicine, Medicine, Disease, business
Published: 2017
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