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2. The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients
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Michaela Prokopova, Friedrich Thaiss, Andries J. Hoitsma, Bruno Hurault de Ligny, Anja Mühlfeld, Séverine Martin, Oliver Gross, Władysław Sułowicz, Annick Massart, Judith Racapé, Miguel Angel Gentil Govantes, A. Yussim, Frieder Keller, Umberto Maggiore, Matthew Howse, Gian Benedetto Piredda, Ricardo Lauzurica, Magali Giral, Luis Antonio Jiménez del Cerro, Marie-Christine Moal, Tomas Reischig, François Glowacki, Jean-François Subra, Bénédicte Janbon, Consuelo De Biase, María José Pérez-Sáez, Marian Klinger, Goce Spasovski, Philippe Gatault, Gaetano La Manna, David Berglund, Cem Tugmen, Giovanni M. Frascà, Uyen Huynh-Do, Christophe Legendre, Annaïck Pallier, Christopher Dudley, Mélanie Chesneau, Laura Braun, Daniel Abramowicz, Karine Hadaya, Christian Noel, Evangeline Pillebout, Carmen Díaz-Corte, Julio Pascual, Ondrej Viklicky, Florence Villemain, Luigi Biancone, Ana Ramírez Puga, Marije C. Baas, Alain Le Moine, Marc Abramowicz, Frederike J. Bemelman, Rainer Oberbauer, Jean-Paul Soulillou, Nurhan Seyahi, Jadranka Buturović Ponikvar, Johan W. de Fijter, Maarten Naesens, Vania Cuna, Klemens Budde, Serhan Tuglular, Pierrick Guerif, Angel Alonso Hernandez, Piero Stratta, Arnaud Garnier, Hulya Colak, K. Clemente, Sophie Brouard, Marc Hazzan, Søren Schwartz Sørensen, Giuseppe Orlando, Daniel Serón, Luboslav Beňa, Quirino Lai, Francesco Pisani, Aisling E. Courtney, Alexandre Dufay, Mehmet Sukru Sever, Thomas Wekerle, Hervé Le Monies De Sagazan, Hakim Mazouz, Aljoša Kandus, Maria Carmen Cantarell, André Gaasbeek, Massart, A, Pallier, A, Pascual, J, Viklicky, O, Budde, K, Spasovski, G, Klinger ,M, Sever, MS, Sørensen, SS, Hadaya, K, Oberbauer, R, Dudley, C, De Fijter, JW, Yussim, A, Hazzan, M, Wekerle, T, Berglund, D, De Biase, C, Pérez-Sáez, MJ, Mühlfeld, A, Orlando, G, Clemente, K, Lai, Q, Pisani, F, Kandus, A, Baas, M, Bemelman, F, Ponikvar, JB, Mazouz ,H, Stratta, P, Subra, JF, Villemain, F, Hoitsma, A, Braun, L, Cantarell, MC, Colak, H, Courtney, A, Frasca, GM, Howse, M, Naesens, M, Reischig, T, Serón, D, Seyahi, N, Tugmen, C, Alonso Hernandez, A, Beňa, L, Biancone, L, Cuna, V, Díaz-Corte, C, Dufay, A, Gaasbeek, A, Garnier, A, Gatault, P, Gentil Govantes, MA, Glowacki, F, Gross, O, Hurault de Ligny, B, Huynh-Do, U, Janbon, B, Jiménez Del Cerro, LA, Keller, F, La Manna, Gaetano, Lauzurica, R, Le Monies De Sagazan, H, Thaiss, F, Legendre, C, Martin, S, Moal, MC, Noël, C, Pillebout, E, Piredda, GB, Puga, AR, Sulowicz, W, Tuglular, S, Prokopova, M, Chesneau, M, Le Moine, A, Guérif, P, Soulillou, JP, Abramowicz, M, Giral, M, Racapé, J, Maggiore, U, Brouard, S, Abramowicz, D, AII - Amsterdam institute for Infection and Immunity, Nephrology, Renal Unit [Brussels, Belgium] (ULB), Université libre de Bruxelles (ULB)-CUB Hôpital Erasme [Bruxelles, Belgium], Medical Genetics Department [Brussels, Belgium], Université libre de Bruxelles (ULB), 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), Nephrology [Barcelona, Spain] (Hospital del Mar), Hospital del Mar [Barcelona, Spain], Department of Nephrology [Prague, Czech Republic] (Transplant Center), Institute for Clinical and Experimental Medicine (IKEM), Department of Nephrology [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Nephrology [Skopje, Macedonia], Ss. Cyril and Methodius University in Skopje, Nephrology and Transplantation Medicine [Wrocław, Poland], University of Wrocław [Poland] (UWr), Internal Medicine, Nephrology [Istanbul, Turkey], Istanbul School of Medicine [Istanbul, Turkey], Nephrology P [Copenhagen, Denmark], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Nephrology and Transplantation [Geneva, Switzerland], Geneva University Hospitals - HUG [Switzerland], Department of Medicine III–Nephrology, Hypertension and Renal Transplantation [Linz, Austria], Krankenhaus Elisabethinen Linz [Linz, Austria], Richard Bright Renal Centre [Bristol, UK], Southmead Hospital [Bristol, UK]-North Bristol NHS Trust [Bristol, UK], Department of Nephrology [Leiden, The Netherlands], Leiden University Medical Center (LUMC), Department of Transplantation [Tel Aviv, Israël] (Rabin Medical Center), Rabin Medical Center [Tel Aviv, Israël]-Tel Aviv University Sackler School of Medicine [Tel Aviv, Israël], Département de Néphrologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Surgery [Vienna, Austria] (Section of Transplantation Immunology), Medizinische Universität Wien = Medical University of Vienna, Section of Clinical Immunology [Uppsala, Sweden] (Department of Immunology, Genetics and Pathology), Uppsala University, UOS Trapianti Rene Pancreas [Parma, Italy] (Centro Trapianti di Parma), Azienda Ospedaliero-Universitaria di Parma, Department of Nephrology [Aachen, Germany], University Hospital Aachen, Section of Transplantation [Winston-Salem, NC, USA] (Department of Surgery), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, U.O.C. Trapianti D’Organo [L’Aquila, Italy], Department of Nephrology [Ljubljana, Slovenia] (Renal Transplantation Centre Ljubljana), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Kidney Diseases [Nijmegen, The Netherlands], Radboudumc Nijmegen [The Netherlands], Renal Transplant Unit [Amsterdam, The Netherlands] (Department of Nephrology), Academic Medical Center [Amsterdam, Netherlands], Unité de Transplantation Rénale et Pancréatique [CHU Sud, Amiens] (Service de Néphrologie), CHU Amiens-Picardie, Department of Translational Medicine [Novara, Italy], Amedeo Avogadro University of Eastern Piedmont, Service de Néphrologie-Dialyse-Transplantation [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), service de Néphrologie et Transplantation Rénale [CHU Strasbourg] (Hôpital de jour de Néphrologie), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg )-Nouvel Hôpital Civil - NHC [Strasbourg], Pediatric Nephrology [Barcelona, Spain] (Vall d’Hebron Hospital), Universitat Autònoma de Barcelona (UAB)-Vall d'Hebron University Hospital [Barcelona], Department of Nephrology [Izmir, Turkey], Tepecik Training and Research Hospital [Izmir, Turkey], Regional Nephrology Unit [Belfast, UK], Belfast City Hospital [Belfast, UK], Nefrologia, Dialisi e Trapianto di rene [Ancona, Italy], AO Torrette Umberto I [Ancona, Italy], Nephrology/Transplantation [Liverpool, UK], Royal Liverpool University Hospital [Liverpool, UK], Department of Nephrology and Renal Transplantation [Leuven, Belgium], University Hospitals Leuven [Leuven]-Catholic University Leuven, Nephrology Ward [Pilsen, Czech Republic] (Department of Internal Medicine), University Hospital Pilsen [Pilsen, Czech Republic], Istanbul University, Servicio de Nefrología, Hospital Universitario, A Coruña, Transplant Centre, University Hospital Louis Pasteur Kosice, University of Turin, St. Orsola University Hospital, University of Bologna, Hospital Universitario Central de Asturias (HUCA), Service Néphrologie [Roubaix], Hôpital Victor Provo, Leids Universitair Medisch Centrum [Leiden, The Netherlands], Néphrologie - Médecine Interne - Hypertension Pédiatrique, Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service Néphrologie - Immunoclinique [CHRU Tours], Hôpital Bretonneau, Hospital Universitario Virgen del Rocío [Sevilla], Service de Néphrologie et Transplantation rénale [CHRU-lille], University Medicine Göttingen, 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), University of Bern [Bern, Switzerland] (University Hospital Bern ), Transplantation rénale [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hospital General Universitario de Alicante, Universitätsklinikum Ulm - University Hospital of Ulm, Hospital Universitario Germans Trias I Pujol, University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hémodialyse et de Néphrologie [Libourne], Hôpital Robert Boulin, CHRU - Service de néphrologie, dialyse et transplantation rénale, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département de Néphrologie et transplantation [Hôpital Saint Louis - APHP], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Kidney Transplant Az. Osp. G. Brotzu, Hospital Universitario Insular de Gran Canaria, University Hospital in Krakow, Marmara School of Medicine Hastanesi, Institute of Transplantation Urology and Nephrology [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Research Center of Epidemiology, Biostatistics and Clinical Research, Nephrology-Renal Transplantation Department, Université libre de Bruxelles (ULB)-Universitair Ziekenhuis Antwerp, ERA-EDTA-DESCARTES working group, the Fonds Erasme (research grant), the Fonds Carine Vyghen, the Fonds Horlait-Dapsens, the RTRS Fondation de Coopération Scientifique CENTAURE and the IHUCesti project., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Ss. Cyril and Methodius University in Skopje (UKIM), Tel Aviv University (TAU)-Rabin Medical Center [Tel Aviv, Israël], Università degli studi di Torino = University of Turin (UNITO), University of Bologna/Università di Bologna, Service Néphrologie, médecine interne et hypertension pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CUB Hôpital Erasme [Bruxelles, Belgium]-Université libre de Bruxelles (ULB), and Hadaya, Karine
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0301 basic medicine ,Nephrology ,Graft Rejection ,Male ,medicine.medical_treatment ,030230 surgery ,Kidney transplant ,0302 clinical medicine ,Surveys and Questionnaires ,Allograft survival ,Kidney transplantation ,ddc:616 ,Graft Survival/immunology ,Survival Rate/trends ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Incidence ,Graft Survival ,Immunosuppression ,operational tolerance ,Transplantation ,3. Good health ,Europe ,Survival Rate ,frequency ,minimally immunosuppressed patients ,Female ,Hemodialysis ,Graft Rejection/epidemiology/immunology/prevention & control ,Homologous ,Adult ,medicine.medical_specialty ,Ronyons -- Trasplantació -- Aspectes immunològics ,Immunosuppression/methods ,kidney transplantation ,Europe/epidemiology ,03 medical and health sciences ,Immune Tolerance/immunology ,Internal medicine ,medicine ,Immune Tolerance ,Humans ,Transplantation, Homologous ,Survival rate ,Immunosuppression Therapy ,graft survival ,business.industry ,medicine.disease ,Kidney Transplantation ,Transplant Recipients ,Surgery ,030104 developmental biology ,Operational tolerance ,Human medicine ,Renal disorders Radboud Institute for Health Sciences [Radboudumc 11] ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Background Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Methods Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many operationally tolerant patients (TOL; defined as having a serum creatinine
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- 2015
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3. Glycated hemoglobin predicts overall and cardiovascular mortality in non-diabetic hemodialysis patients
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Ercan Ok, Gulay Asci, Savas Sipahi, Fatih Kircelli, Ziya Omer, Hamad Dheir, Ebru Sevinc Ok, Huseyin Toz, Devrim Bozkurt, Eberhard Ritz, Mehmet Sukru Sever, Mehmet Ozkahya, Osman Zikrullah Sahin, Muhittin Ertilav, Ok, ES, Asci, G, Toz, H, Ritz, E, Kircelli, F, Sever, MS, Ozkahya, M, Sipahi, S, Dheir, H, Bozkurt, D, Omer, Z, Sahin, OZ, Ertilav, M, Ok, E, Sakarya Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri Bölümü, Sipahi, Savaş, and Dheir, Hamad
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,Turkey ,endocrine system diseases ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Risk Assessment ,law.invention ,chemistry.chemical_compound ,Randomized controlled trial ,Predictive Value of Tests ,Renal Dialysis ,Risk Factors ,law ,Cause of Death ,Internal medicine ,Humans ,Medicine ,Prospective Studies ,Renal Insufficiency, Chronic ,Prospective cohort study ,Aged ,Proportional Hazards Models ,Cause of death ,Glycated Hemoglobin ,Chi-Square Distribution ,business.industry ,Proportional hazards model ,nutritional and metabolic diseases ,General Medicine ,Middle Aged ,Urology & Nephrology ,chemistry ,Cardiovascular Diseases ,Nephrology ,Predictive value of tests ,Multivariate Analysis ,Female ,Hemodialysis ,Glycated hemoglobin ,business ,Chi-squared distribution ,Biomarkers - Abstract
Aims: Besides diabetic patients, glycated hemoglobin (HbA(1c)) levels have been reported to predict mortality in non-diabetics patients. However, the importance of HbA(1c) levels in non-diabetic hemodialysis patients still remains unknown. Thus, we aimed to prospectively investigate the impact of HbA(1c) on all-cause and cardiovascular mortality in a large group of prevalent non-diabetic hemodialysis patients. Methods: HbA(1c) was measured quarterly in 489 non-diabetic prevalent hemodialysis patients. Overall and cardiovascular mortality were evaluated over a 3 year follow-up. Results: Mean HbA(1c) level was 4.88 +/- 0.46% (3.5 - 6.9%). During the 28.3 +/- 10.6 months follow-up period, 67 patients (13.7%) died; 31 from cardiovascular causes. In Kaplan-Meier analysis, patients in the lowest (< 4.69%) and highest HbA(1c) (> 5.04%) tertiles had poorer overall survival compared to the middle HbA(1c) tertile (p < 0.001). Adjusted Cox-regression analysis revealed that the highest HbA(1c) tertile was associated with both overall (HR = 3.60, 95% CI 1.57 - 8.27, p = 0.002) and cardiovascular (HR = 6.66, 95% CI 1.51 - 29.4; p = 0.01) mortality. Also, low HbA(1c) levels tended to be associated with overall mortality (HR = 2.26, 95% CI 0.96 - 5.29, p = 0.06). Conclusion: Upper normal HbA(1c) levels are independently associated with cardiovascular and overall mortality in non-diabetic hemodialysis patients, whereas lower HbA(1c) levels are not.
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- 2014
4. Ethics in humanitarian settings-relevance and consequences for dialysis and kidney care.
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Luyckx VA, Van Biesen W, Ponikvar JB, Heering P, Abu-Alfa A, Silberzweig J, Fontana M, Tuglular S, and Sever MS
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With the increasing frequency and severity of disasters and the increasing number of patients living with kidney disease, on dialysis and with transplants around the world, the need for kidney care in humanitarian settings is increasing. Almost all humanitarian emergencies pose a threat to kidney health because all treatments are highly susceptible to interruption, and interruption can be deadly. Providing support for people requiring dialysis in humanitarian settings can be complex and is associated with many trade-offs. The global kidney care community must become familiar with the ethics, principles and duties essential to meeting the overarching goals of ethical and effective disaster relief. Ethics principles and values must be considered on the individual, public health and global levels. The wellbeing of a single patient must be considered in the context of the competing needs of many others, and optimal treatment may not be possible due to resource constraints. Public health ethics principles, including considerations of triage and resource allocation, maximization of benefit and feasibility, often become directly relevant at the bedside. Individuals delivering humanitarian relief must be well trained, competent, respectful and professional, while involved organizations need to uphold the highest professional and ethical standards. There may be dissonance between ethical guidance and practical realities in humanitarian settings, which for inexperienced individuals may present significant challenges. Sustaining dialysis care in emergencies brings these issues starkly to the fore. Preparedness for dialysis in emergencies is an ethical imperative that mandates multisectoral stakeholder engagement and action, development of surge response plans, clinical and ethics guidance, and transparent priority setting. This manuscript outlines common ethics challenges and considerations that apply in all humanitarian actions, and illustrates their relevance to kidney care as a whole, using examples of how these may apply to dialysis and kidney disaster relief efforts in humanitarian settings., Competing Interests: All authors declare no conflicts of interest with relevance to this work., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)
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- 2024
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5. Destructive disasters, trauma, crush syndrome, and beyond.
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Sever MS, Katı YA, and Özkaya U
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- Humans, Crush Syndrome therapy, Crush Syndrome complications, Disasters, Acute Kidney Injury etiology, Rhabdomyolysis diagnosis, Rhabdomyolysis etiology, Rhabdomyolysis therapy, Fractures, Bone complications
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Orthopedic injuries, especially fractures of long bones as well as multiple fractures and comminuted fractures, are very common after destructive disasters (e.g., earthquakes, wars, and hurricanes). Another frequent problem is traumatic rhabdomyolysis, which may result in crush syndrome, the second most frequent cause of death after direct traumatic impact following earthquakes. To improve outcomes, interventions should be initiated even before extrication of the victims, which include maintenance of airway patency and spine stabilization, stopping traumatic bleeding by any means, and initiating fluid resuscitation. On-site amputations have been extensively debated to liberate the victims if the release of trapped limbs is impossible. Early after the rescue, a primary survey and triage are performed, a fluid resuscitation policy is planned, complications are treated, the wounds are decontaminated, and the victim is transported to specialized hospitals. A triage and primary survey are also performed at admission to the hospitals, which are followed by a secondary survey, physical, laboratory, and imaging examinations. Washing and cleaning of the soft-tissue injuries and debridement in open, necrotic wounds are vital. Applications of fasciotomies and amputations are controversial since they are associated with both benefits and serious complications; therefore, clear indications should be defined. Crush syndrome has been described as the presence of systemic manifestations following traumatic rhabdomyolysis, the most important component of which is acute kidney injury that may contribute to fatal hyperkalemia. The overall mortality rate is around 20% in crushed patients, which underlines the importance of prevention. Treatment includes maintaining of fluid electrolyte and acid-base balance, application of dialysis, and also prevention and treatment of complications. The principles and practices in disaster medicine may differ from those applied in routine practice; therefore, organizing repeated training courses may be helpful to provide the most effective healthcare and to save as many lives as possible after mass disasters.
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- 2023
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6. Novel transcriptomic signatures associated with premature kidney allograft failure.
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Hruba P, Klema J, Le AV, Girmanova E, Mrazova P, Massart A, Maixnerova D, Voska L, Piredda GB, Biancone L, Puga AR, Seyahi N, Sever MS, Weekers L, Muhfeld A, Budde K, Watschinger B, Miglinas M, Zahradka I, Abramowicz M, Abramowicz D, and Viklicky O
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Background: The power to predict kidney allograft outcomes based on non-invasive assays is limited. Assessment of operational tolerance (OT) patients allows us to identify transcriptomic signatures of true non-responders for construction of predictive models., Methods: In this observational retrospective study, RNA sequencing of peripheral blood was used in a derivation cohort to identify a protective set of transcripts by comparing 15 OT patients (40% females), from the TOMOGRAM Study (NCT05124444), 14 chronic active antibody-mediated rejection (CABMR) and 23 stable graft function patients ≥15 years (STA). The selected differentially expressed transcripts between OT and CABMR were used in a validation cohort (n = 396) to predict 3-year kidney allograft loss at 3 time-points using RT-qPCR., Findings: Archetypal analysis and classifier performance of RNA sequencing data showed that OT is clearly distinguishable from CABMR, but similar to STA. Based on significant transcripts from the validation cohort in univariable analysis, 2 multivariable Cox models were created. A 3-transcript (ADGRG3, ATG2A, and GNLY) model from POD 7 predicted graft loss with C-statistics (C) 0.727 (95% CI, 0.638-0.820). Another 3-transcript (IGHM, CD5, GNLY) model from M3 predicted graft loss with C 0.786 (95% CI, 0.785-0.865). Combining 3-transcripts models with eGFR at POD 7 and M3 improved C-statistics to 0.860 (95% CI, 0.778-0.944) and 0.868 (95% CI, 0.790-0.944), respectively., Interpretation: Identification of transcripts distinguishing OT from CABMR allowed us to construct models predicting premature graft loss. Identified transcripts reflect mechanisms of injury/repair and alloimmune response when assessed at day 7 or with a loss of protective phenotype when assessed at month 3., Funding: Supported by the Ministry of Health of the Czech Republic under grant NV19-06-00031., Competing Interests: Declaration of interests All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/. All authors declare no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
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- 2023
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7. Distribution, preparedness and management of Ukrainian adult refugees on dialysis-an international survey by the Renal Disaster Relief Task Force of the European Renal Association.
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Pawłowicz-Szlarska E, Vanholder R, Sever MS, Tuğlular S, Luyckx V, Eckardt KU, Gallego D, Ivanov D, Nistor I, Shroff R, Škoberne A, Stuard S, Gellert R, Noruišiene E, Sekkarie M, and Wiecek A
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- Female, Humans, Adult, Middle Aged, Male, Renal Dialysis, Cross-Sectional Studies, Surveys and Questionnaires, Refugees, Disasters
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Background: Due to the Russian-Ukrainian war, some of the about 10 000 adults requiring dialysis in Ukraine fled their country to continue dialysis abroad. To better understand the needs of conflict-affected dialysis patients, the Renal Disaster Relief Task Force of the European Renal Association conducted a survey on distribution, preparedness and management of adults requiring dialysis who were displaced due to the war., Methods: A cross-sectional online survey was sent via National Nephrology Societies across Europe and disseminated to their dialysis centers. Fresenius Medical Care shared a set of aggregated data., Results: Data were received on 602 patients dialyzed in 24 countries. Most patients were dialyzed in Poland (45.0%), followed by Slovakia (18.1%), Czech Republic (7.8%) and Romania (6.3%). The interval between last dialysis and the first in the reporting center was 3.1 ± 1.6 days, but was ≥4 days in 28.1% of patients. Mean age was 48.1 ± 13.4 years, 43.5% were females. Medical records were carried by 63.9% of patients, 63.3% carried a list of medications, 60.4% carried the medications themselves and 44.0% carried their dialysis prescription, with 26.1% carrying all of these items and 16.1% carrying none. Upon presentation outside Ukraine, 33.9% of patients needed hospitalization. Dialysis therapy was not continued in the reporting center by 28.2% of patients until the end of the observation period., Conclusions: We received information about approximately 6% of Ukrainian dialysis patients, who had fled their country by the end of August 2022. A substantial proportion were temporarily underdialyzed, carried incomplete medical information and needed hospitalization. The results of our survey may help to inform policies and targeted interventions to respond to the special needs of this vulnerable population during wars and other disasters in the future., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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8. Lessons learned during the war in Ukraine: a report from the Renal Disaster Relief Task Force of the ERA.
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Tuğlular S, Luyckx V, Vanholder R, Skoberne A, Wiecek A, Nistor İ, Pawlowicz-Szlarska E, Shroff R, Ivanov D, Eckardt KU, Noruisiene E, Gallego D, Loboda O, and Sever MS
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- Humans, Ukraine epidemiology, Renal Dialysis, Kidney, Disasters, Kidney Diseases epidemiology, Kidney Diseases therapy
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People living with kidney disease are among the most vulnerable at times of natural or man-made disasters. In addition to their unpredictable course, armed conflicts impose a major threat given the disruption of infrastructure, sanitation and access to food, water and medical care. The ongoing war in Ukraine has once more demonstrated the importance of preparedness, organization, coordination and solidarity during disasters. People living with kidney disease face serious challenges given their dependence on life-sustaining treatment, irrespective of whether they remain in the war zone or are displaced internally or externally. This especially affects those requiring kidney replacement therapy, dialysis or transplantation, but also patients with other kidney diseases and the medical staff who care for them. Soon after the war started, the European Renal Association assigned a Renal Disaster Relief Task Force dedicated to support the people living with kidney disease and the nephrology community in Ukraine. This report summarizes the major challenges faced, actions taken and lessons learned by this task force. We anticipate that the experience will help to increase preparedness and mitigate the devastating effects of armed conflicts on the kidney community in the future and propose to establish an international collaboration to extend this effort to other parts of the world facing similar challenges., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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9. The 3-Step Model of informed consent for living kidney donation: a proposal on behalf of the DESCaRTES Working Group of the European Renal Association.
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Grossi AA, Sever MS, Hellemans R, Mariat C, Crespo M, Watschinger B, Peruzzi L, Demir E, Velioglu A, Gandolfini I, Oniscu GC, Hilbrands L, and Mjoen G
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- Humans, Informed Consent, Tissue and Organ Harvesting, Living Donors, Kidney, Kidney Transplantation education
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Living donation challenges the ethical principle of non-maleficence in that it exposes healthy persons to risks for the benefit of someone else. This makes safety, informed consent (IC) and education a priority. Living kidney donation has multiple benefits for the potential donor, but there are also several known short- and long-term risks. Although complete standardization of IC is likely to be unattainable, studies have emphasized the need for a standardized IC process to enable equitable educational and decision-making prospects for the prevention of inequities across transplant centers. Based on the Three-Talk Model of shared decision-making by Elwyn et al., we propose a model, named 3-Step (S) Model, where each step coincides with the three ideal timings of the process leading the living donor to the decision to pursue living donation: prior to the need for kidney replacement therapy (team talk); at the local nephrology unit or transplant center, with transplant clinicians and surgeons prior to evaluations start (option talk); and throughout evaluation, after having learned about the different aspects of donation, especially if there are second thoughts or doubts (decision talk). Based on the 3-S Model, to deliver conceptual and practical guidance to nephrologists and transplant clinicians, we provide recommendations for standardization of the timing, content, modalities for communicating risks and assessment of understanding prior to donation. The 3-S Model successfully allows an integration between standardization and individualization of IC, enabling a person-centered approach to potential donors. Studies will assess the effectiveness of the 3-S Model in kidney transplant clinical practice., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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10. An exome-wide study of renal operational tolerance.
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Massart A, Danger R, Olsen C, Emond MJ, Viklicky O, Jacquemin V, Soblet J, Duerinckx S, Croes D, Perazzolo C, Hruba P, Daneels D, Caljon B, Sever MS, Pascual J, Miglinas M, Pirson I, Ghisdal L, Smits G, Giral M, Abramowicz D, Abramowicz M, and Brouard S
- Abstract
Background: Renal operational tolerance is a rare and beneficial state of prolonged renal allograft function in the absence of immunosuppression. The underlying mechanisms are unknown. We hypothesized that tolerance might be driven by inherited protein coding genetic variants with large effect, at least in some patients., Methods: We set up a European survey of over 218,000 renal transplant recipients and collected DNAs from 40 transplant recipients who maintained good allograft function without immunosuppression for at least 1 year. We performed an exome-wide association study comparing the distribution of moderate to high impact variants in 36 tolerant patients, selected for genetic homogeneity using principal component analysis, and 192 controls, using an optimal sequence-kernel association test adjusted for small samples., Results: We identified rare variants of HOMER2 (3/36, FDR 0.0387), IQCH (5/36, FDR 0.0362), and LCN2 (3/36, FDR 0.102) in 10 tolerant patients vs . 0 controls. One patient carried a variant in both HOMER2 and LCN2 . Furthermore, the three genes showed an identical variant in two patients each. The three genes are expressed at the primary cilium, a key structure in immune responses., Conclusion: Rare protein coding variants are associated with operational tolerance in a sizable portion of patients. Our findings have important implications for a better understanding of immune tolerance in transplantation and other fields of medicine.ClinicalTrials.gov, identifier: NCT05124444., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Massart, Danger, Olsen, Emond, Viklicky, Jacquemin, Soblet, Duerinckx, Croes, Perazzolo, Hruba, Daneels, Caljon, Sever, Pascual, Miglinas, the Renal Tolerance Investigators, Pirson, Ghisdal, Smits, Giral, Abramowicz, Abramowicz and Brouard.)
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- 2023
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11. Efficacy and safety of interleukin-1 blockers in kidney transplant recipients with familial Mediterranean fever: a propensity score-matched cohort study.
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Mirioglu S, Dirim AB, Bektas M, Demir E, Tor YB, Ozluk Y, Kilicaslan I, Oto OA, Yalcinkaya Y, Caliskan Y, Artim-Esen B, Yazici H, Inanc M, Turkmen A, Gul A, and Sever MS
- Subjects
- Humans, Cohort Studies, Colchicine, Interleukin 1 Receptor Antagonist Protein therapeutic use, Interleukin-1, Retrospective Studies, C-Reactive Protein, Propensity Score, Proteinuria complications, Familial Mediterranean Fever complications, Familial Mediterranean Fever drug therapy, Kidney Transplantation adverse effects
- Abstract
Background: Data on use of interleukin (IL)-1 blockers in kidney transplant recipients (KTRs) with familial Mediterranean fever (FMF) are very limited. We aimed to evaluate the efficacy and safety of anakinra and canakinumab in the transplantation setting., Methods: In this retrospective cohort study, we included KTRs who suffered from AA amyloidosis caused by FMF and treated with anakinra or canakinumab (study group, n = 36). Using propensity score matching, we selected 36 patients without FMF or amyloidosis from our database of 696 KTRs as the control group. Primary outcomes were patient and graft survival. Biopsy-confirmed graft rejection, changes in estimated glomerular filtration rate (eGFR), high-sensitivity CRP (hsCRP), erythrocyte sedimentation rate (ESR), proteinuria and number of monthly attacks were secondary outcomes., Results: All KTRs with FMF began IL-1 blocker therapy with anakinra and nine (25%) were switched to canakinumab. Overall death was more frequent in the study group (19.4% vs 0%) (P = .005); however, overall graft loss was comparable between study (27.8%) and control groups (36.1%) (P = .448). Five- and 10-year graft survival rates were significantly higher in the study group (94.4% and 83.3%, respectively) than in the control group (77.8% and 63.9%, respectively) (P = .014 and P < .001, respectively). Rejections were numerically lower in study group (8.3% vs 25%), but it did not reach to statistical significance (P = .058). When compared with the pre-treatment period, with IL-1 blockers, the number of attacks per month (P < .001), and eGFR (P = .004), hsCRP (P < .001) and ESR (P = .026) levels were lower throughout the follow-up, whereas proteinuria levels were not., Conclusions: Anakinra and canakinumab are effective in KTRs suffering from FMF; however, the mortality rate may be of concern., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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12. Kidney transplantation during mass disasters - from COVID-19 to other catastrophes A Consensus Statement by the DESCARTES Working Group and Ethics Committee of the ERA.
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Sever MS, Vanholder R, Oniscu G, Abramowicz D, Van Biesen W, Maggiore U, Watschinger B, Mariat C, Buturovic-Ponikvar J, Crespo M, Mjoen G, Heering P, Peruzzi L, Gandolfini I, Hellemans R, and Hilbrands L
- Subjects
- Humans, Ethics Committees, Pandemics prevention & control, COVID-19 epidemiology, COVID-19 prevention & control, Disasters, Kidney Transplantation
- Abstract
Mass disasters are characterized by a disparity between health care demand and supply, which hampers complex therapies like kidney transplantation. Considering scarcity of publications on previous disasters, we reviewed transplantation practice during the recent COVID-19 pandemic, and dwelled upon this experience for guiding transplantation strategies in the future pandemic and non-pandemic catastrophes. We strongly suggest continuing transplantation programs during mass disasters, if medical and logistic operational circumstances are appropriate. Postponing transplantations from living donors and referral of urgent cases to safe regions or hospitals are justified. Specific preventative measures in anticipated disasters (such as vaccination programs during pandemics or evacuation in case of hurricanes or wars) may be useful to minimize risks. Immunosuppressive therapies should consider stratifying risk status and avoiding heavy immune suppression in patients with a low probability of therapeutic success. Discharging patients at the earliest convenience is justified during pandemics, whereas delaying discharge is reasonable in other disasters, if infrastructural damage results in unhygienic living environments for the patients. In the outpatient setting, telemedicine is a useful approach to reduce the patient load to hospitals, to minimize the risk of nosocomial transmission in pandemics and the need for transport in destructive disasters. If it comes down to save as many lives as possible, some ethical principles may vary in function of disaster circumstances, but elementary ethical rules are non-negotiable. Patient education is essential to minimize disaster-related complications and to allow for an efficient use of health care resources., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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13. Armed conflicts and kidney patients: a consensus statement from the Renal Disaster Relief Task Force of the ERA.
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Sever MS, Vanholder R, Luyckx V, Eckardt KU, Kolesnyk M, Wiecek A, Pawlowicz-Szlarska E, Gallego D, Shroff R, Škoberne A, Nistor I, Sekkarie M, Ivanov D, Noruišiene E, and Tuglular S
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- Humans, Renal Dialysis adverse effects, Kidney, Armed Conflicts, Disasters, Acute Kidney Injury etiology
- Abstract
During conflicts, people with kidney disease, either those remaining in the affected zones or those who are displaced, may be exposed to additional threats because of medical and logistical challenges. Acute kidney injury developing on the battlefield, in field hospitals or in higher-level hospital settings is characterized by poor outcomes. People with chronic kidney disease may experience treatment interruptions, contributing to worsening kidney function. Patients living on dialysis or with a functioning graft may experience limitations of dialysis possibilities or availability of immunosuppressive medications, increasing the risk of severe complications including death. When patients must flee, these threats are compounded by unhealthy and insecure conditions both during displacement and/or at their destination. Measures to attenuate these risks may only be partially effective. Local preparedness for overall and medical/kidney-related disaster response is essential. Due to limitations in supply, adjustments in dialysis frequency or dose, switching between hemodialysis and peritoneal dialysis and changes in immunosuppressive regimens may be required. Telemedicine (if possible) may be useful to support inexperienced local physicians in managing medical and logistical challenges. Limited treatment possibilities during warfare may necessitate referral of patients to distant higher-level hospitals, once urgent care has been initiated. Preparation for disasters should occur ahead of time. Inclusion of disaster nephrology in medical and nursing curricula and training of patients, families and others on self-care and medical practice in austere settings may enhance awareness and preparedness, support best practices adapted to the demanding circumstances and prepare non-professionals to lend support., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)
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- 2023
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14. Issues regarding COVID-19 in kidney transplantation in the ERA of the Omicron variant: a commentary by the ERA Descartes Working Group.
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Gandolfini I, Crespo M, Hellemans R, Maggiore U, Mariat C, Mjoen G, Oniscu GC, Peruzzi L, Sever MS, Watschinger B, and Hilbrands L
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- Antiviral Agents, Humans, Living Donors, SARS-CoV-2, COVID-19 epidemiology, Kidney Transplantation adverse effects
- Abstract
The Omicron variant, which has become the dominant strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, brings new challenges to preventing and controlling the infection. Moreover, the widespread implementation of vaccination policies before and after transplantation, and the development of new prophylactic and treatment strategies for coronavirus disease 2019 (COVID-19) over the past 12-18 months, has raised several new issues concerning kidney transplant recipients. In this special report, the ERA DESCARTES (Developing Education Science and Care for Renal Transplantation in European States) Working Group addresses several questions related to everyday clinical practice concerning kidney transplant recipients and to the assessment of deceased and live kidney donors: what is the current risk of severe disease and of breakthrough infection, the optimal management of immunosuppression in kidney transplant recipients with COVID-19, the role of passive immunization and the efficacy of antiviral drugs in ambulatory patients, the management of drug-to-drug interactions, safety criteria for the use of SARS-CoV-2-positive donors, issues related to the use of T cell depleting agents as induction treatment, and current recommendations for shielding practices., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)
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- 2022
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15. Assessment of pre-donation glomerular filtration rate: going back to basics.
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Mariat C, Mjøen G, Watschinger B, Sever MS, Crespo M, Peruzzi L, Oniscu GC, Abramowicz D, Hilbrands L, and Maggiore U
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- Glomerular Filtration Rate, Humans, Kidney, Living Donors, Donor Selection, Kidney Transplantation
- Abstract
The 2017 version of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines is the most recent international framework for the evaluation and care of living kidneys donors. Along with the call for an integrative approach evaluating the long-term end-stage kidney disease risk for the future potential donor, several recommendations are formulated regarding the pre-donation glomerular filtration rate (GFR) adequacy with no or little consideration for the donor candidate's age or for the importance of using reference methods of GFR measurements. Herein, we question the position of the KDIGO guidelines and discuss the rationale and modalities for a more basic, but no less demanding GFR evaluation enabling a more efficient selection of potential kidney donors., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)
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- 2022
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16. Management of obesity in kidney transplant candidates and recipients: A clinical practice guideline by the DESCARTES Working Group of ERA.
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Oniscu GC, Abramowicz D, Bolignano D, Gandolfini I, Hellemans R, Maggiore U, Nistor I, O'Neill S, Sever MS, Koobasi M, and Nagler EV
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- Humans, Obesity complications, Obesity surgery, Renal Dialysis, Tissue Donors, Transplant Recipients, Kidney Failure, Chronic surgery, Kidney Transplantation
- Abstract
The clinical practice guideline Management of Obesity in Kidney Transplant Candidates and Recipients was developed to guide decision-making in caring for people with end-stage kidney disease (ESKD) living with obesity. The document considers the challenges in defining obesity, weighs interventions for treating obesity in kidney transplant candidates as well as recipients and reflects on the impact of obesity on the likelihood of wait-listing as well as its effect on transplant outcomes. It was designed to inform management decisions related to this topic and provide the backdrop for shared decision-making. This guideline was developed by the European Renal Association's Developing Education Science and Care for Renal Transplantation in European States working group. The group was supplemented with selected methodologists to supervise the project and provide methodological expertise in guideline development throughout the process. The guideline targets any healthcare professional treating or caring for people with ESKD being considered for kidney transplantation or having received a donor kidney. This includes nephrologists, transplant physicians, transplant surgeons, general practitioners, dialysis and transplant nurses. Development of this guideline followed an explicit process of evidence review. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendations Assessment, Development and Evaluation approach. Limitations of the evidence are discussed and areas of future research are presented., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)
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- 2021
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17. LIMS1 risk genotype and T cell-mediated rejection in kidney transplant recipients.
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Caliskan Y, Karahan G, Akgul SU, Mirioglu S, Ozluk Y, Yazici H, Demir E, Dirim AB, Turkmen A, Edwards J, Savran FO, Sever MS, Kiryluk K, Gharavi A, and Lentine KL
- Subjects
- Adaptor Proteins, Signal Transducing, Allografts, Genotype, Graft Rejection etiology, Graft Rejection genetics, Graft Survival, Humans, LIM Domain Proteins, Membrane Proteins, T-Lymphocytes, Transplant Recipients, Kidney Transplantation adverse effects
- Abstract
Background: This study aims to examine the association of LIM zinc finger domain containing 1 (LIMS1) genotype with allograft rejection in an independent kidney transplant cohort., Methods: We genotyped 841 kidney transplant recipients for the LIMS1 rs893403 variant by Sanger sequencing followed by polymerase chain reaction confirmation of the deletion. Recipients who were homozygous for the LIMS1 rs893403 genotype GG were compared with the AA/AG genotypes. The primary outcome was T cell-mediated or antibody-mediated rejection (TCMR or ABMR, respectively) and secondary outcome was allograft loss., Results: After a median follow-up of 11.4 years, the rate of TCMR was higher in recipients with the GG genotype (n = 200) compared with the AA/AG genotypes (n = 641) [25 (12.5%) versus 35 (5.5%); P = 0.001] while ABMR did not differ by genotype [18 (9.0%) versus 62 (9.7%)]. Recipients with the GG genotype had 2.4 times higher risk of TCMR than those who did not have this genotype [adjusted hazard ratio2.43 (95% confidence interval 1.44-4.12); P = 0.001]. A total of 189 (22.5%) recipients lost their allografts during follow-up. Kaplan-Meier estimates of 5-year (94.3% versus 94.4%; P = 0.99) and 10-year graft survival rates (86.9% versus 83.4%; P = 0.31) did not differ significantly in the GG versus AA/AG groups., Conclusions: Our study demonstrates that recipient LIMS1 risk genotype is associated with an increased risk of TCMR after kidney transplantation, confirming the role of the LIMS1 locus in allograft rejection. These findings may have clinical implications for the prediction and clinical management of kidney transplant rejection by pretransplant genetic testing of recipients and donors for LIMS1 risk genotype., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
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- 2021
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18. COVID-19-related mortality in kidney transplant and haemodialysis patients: a comparative, prospective registry-based study.
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Goffin E, Candellier A, Vart P, Noordzij M, Arnol M, Covic A, Lentini P, Malik S, Reichert LJ, Sever MS, Watschinger B, Jager KJ, and Gansevoort RT
- Subjects
- Humans, Registries, Renal Dialysis, Risk Factors, SARS-CoV-2, Transplant Recipients, COVID-19, Kidney Failure, Chronic therapy, Kidney Transplantation adverse effects
- Abstract
Background: Coronavirus disease 2019 (COVID-19) has exposed haemodialysis (HD) patients and kidney transplant (KT) recipients to an unprecedented life-threatening infectious disease, raising concerns about kidney replacement therapy (KRT) strategy during the pandemic. This study investigated the association of the type of KRT with COVID-19 severity, adjusting for differences in individual characteristics., Methods: Data on KT recipients and HD patients diagnosed with COVID-19 between 1 February 2020 and 1 December 2020 were retrieved from the European Renal Association COVID-19 Database. Cox regression models adjusted for age, sex, frailty and comorbidities were used to estimate hazard ratios (HRs) for 28-day mortality risk in all patients and in the subsets that were tested because of symptoms., Results: A total of 1670 patients (496 functional KT and 1174 HD) were included; 16.9% of KT and 23.9% of HD patients died within 28 days of presentation. The unadjusted 28-day mortality risk was 33% lower in KT recipients compared with HD patients {HR 0.67 [95% confidence interval (CI) 0.52-0.85]}. In a fully adjusted model, the risk was 78% higher in KT recipients [HR 1.78 (95% CI 1.22-2.61)] compared with HD patients. This association was similar in patients tested because of symptoms [fully adjusted model HR 2.00 (95% CI 1.31-3.06)]. This risk was dramatically increased during the first post-transplant year. Results were similar for other endpoints (e.g. hospitalization, intensive care unit admission and mortality >28 days) and across subgroups., Conclusions: KT recipients had a greater risk of a more severe course of COVID-19 compared with HD patients, therefore they require specific infection mitigation strategies., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)
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- 2021
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19. Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups.
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Mjøen G, Maggiore U, Kessaris N, Kimenai D, Watschinger B, Mariat C, Sever MS, Crespo M, Peruzzi L, Spasovski G, Sørensen SS, Heemann U, Pascual J, Viklicky O, Courtney AE, Hadaya K, Wagner L, Nistor I, Hadjianastassiou V, Durlik M, Helanterä I, Oberbauer R, Oniscu G, Hilbrands L, and Abramowicz D
- Subjects
- Humans, Kidney, Living Donors, Surveys and Questionnaires, Tissue and Organ Harvesting, Kidney Transplantation adverse effects
- Abstract
Background: Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation., Methods: All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks., Results: The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes., Conclusions: The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)
- Published
- 2021
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20. Risk factors, pathogenesis, presentation and management of BK virus infection in kidney transplantation.
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Demir E, Turkmen A, and Sever MS
- Published
- 2021
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21. Mass Disasters and Burnout in Nephrology Personnel: From Earthquakes and Hurricanes to COVID-19 Pandemic.
- Author
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Sever MS, Ortiz A, Maggiore U, Bac-García E, and Vanholder R
- Subjects
- Burnout, Psychological prevention & control, Disaster Planning, Humans, Burnout, Psychological epidemiology, COVID-19 epidemiology, Cyclonic Storms, Earthquakes, Health Personnel, Nephrology, SARS-CoV-2
- Abstract
Mass disasters result in extensive health problems and make health care delivery problematic, as has been the case during the COVID-19 pandemic. Although COVID-19 was initially considered a pulmonary problem, it soon became clear that various other organs were involved. Thus, many care providers, including kidney health personnel, were overwhelmed or developed burnout. This review aims to describe the spectrum of burnout in mass disasters and suggests solutions specifically for nephrology personnel by extending previous experience to the COVID-19 pandemic. Burnout (a psychologic response to work-related stress) is already a frequent part of routine nephrology practice and, not surprisingly, is even more common during mass disasters due to increased workload and specific conditions, in addition to individual factors. Avoiding burnout is essential to prevent psychologic and somatic health problems in personnel as well as malpractice, understaffing, and inadequate health care delivery, all of which increase the health care burden of disasters. Burnout may be prevented by predisaster organizational measures, which include developing an overarching plan and optimizing health care infrastructure, and ad hoc disaster-specific measures that encompass both organizational and individual measures. Organizational measures include increasing safety, decreasing workload and fear of malpractice, optimizing medical staffing and material supplies, motivating personnel, providing mental health support, and enabling flexibility in working circumstances. Individual measures include training on coping with stress and problematic conditions, minimizing the stigma of emotional distress, and maintaining physical health. If these measures fall short, asking for external help is mandatory to avoid an inefficient disaster health care response. Minimizing burnout by applying these measures will improve health care provision, thus saving as many lives as possible., (Copyright © 2021 by the American Society of Nephrology.)
- Published
- 2021
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22. How should I manage immunosuppression in a kidney transplant patient with COVID-19? An ERA-EDTA DESCARTES expert opinion.
- Author
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Maggiore U, Abramowicz D, Crespo M, Mariat C, Mjoen G, Peruzzi L, Sever MS, Oniscu GC, Hilbrands L, and Watschinger B
- Subjects
- Betacoronavirus, COVID-19, Coronavirus Infections, Edetic Acid, Humans, Immunosuppression Therapy, Pandemics, Pneumonia, Viral, SARS-CoV-2, Transplant Recipients, Kidney Transplantation
- Published
- 2020
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23. The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis.
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Xie J, Liu L, Mladkova N, Li Y, Ren H, Wang W, Cui Z, Lin L, Hu X, Yu X, Xu J, Liu G, Caliskan Y, Sidore C, Balderes O, Rosen RJ, Bodria M, Zanoni F, Zhang JY, Krithivasan P, Mehl K, Marasa M, Khan A, Ozay F, Canetta PA, Bomback AS, Appel GB, Sanna-Cherchi S, Sampson MG, Mariani LH, Perkowska-Ptasinska A, Durlik M, Mucha K, Moszczuk B, Foroncewicz B, Pączek L, Habura I, Ars E, Ballarin J, Mani LY, Vogt B, Ozturk S, Yildiz A, Seyahi N, Arikan H, Koc M, Basturk T, Karahan G, Akgul SU, Sever MS, Zhang D, Santoro D, Bonomini M, Londrino F, Gesualdo L, Reiterova J, Tesar V, Izzi C, Savoldi S, Spotti D, Marcantoni C, Messa P, Galliani M, Roccatello D, Granata S, Zaza G, Lugani F, Ghiggeri G, Pisani I, Allegri L, Sprangers B, Park JH, Cho B, Kim YS, Kim DK, Suzuki H, Amoroso A, Cattran DC, Fervenza FC, Pani A, Hamilton P, Harris S, Gupta S, Cheshire C, Dufek S, Issler N, Pepper RJ, Connolly J, Powis S, Bockenhauer D, Stanescu HC, Ashman N, Loos RJF, Kenny EE, Wuttke M, Eckardt KU, Köttgen A, Hofstra JM, Coenen MJH, Kiemeney LA, Akilesh S, Kretzler M, Beck LH, Stengel B, Debiec H, Ronco P, Wetzels JFM, Zoledziewska M, Cucca F, Ionita-Laza I, Lee H, Hoxha E, Stahl RAK, Brenchley P, Scolari F, Zhao MH, Gharavi AG, Kleta R, Chen N, and Kiryluk K
- Subjects
- Alleles, Amino Acid Sequence, Asian People genetics, Case-Control Studies, Glomerulonephritis, Membranous immunology, Humans, Interferon Regulatory Factors genetics, Models, Molecular, NF-kappa B p50 Subunit genetics, Polymorphism, Single Nucleotide, Receptors, Phospholipase A2 genetics, White People genetics, Genome-Wide Association Study, Glomerulonephritis, Membranous diagnosis, Glomerulonephritis, Membranous genetics
- Abstract
Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 × 10
-12 ) and IRF4 (rs9405192, OR = 1.29, P = 1.4 × 10-14 ), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 × 10-103 ) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 × 10-49 ), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 × 10-93 ), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 × 10-23 and OR = 3.39, P = 5.2 × 10-82 , respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk.- Published
- 2020
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24. Nephrology and Public Policy Committee propositions to stimulate research collaboration in adults and children in Europe.
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Massy ZA, Caskey FJ, Finne P, Harambat J, Jager KJ, Nagler E, Stengel B, Sever MS, Vanholder R, Blankestijn PJ, Bruchfeld A, Capasso G, Fliser D, Fouque D, Goumenos D, Soler MJ, Rychlík I, Spasovski G, Stevens K, Wanner C, and Zoccali C
- Published
- 2019
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25. Infectious Complications of Induction Therapies in Kidney Transplantation.
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Bayraktar A, Catma Y, Akyildiz A, Demir E, Bakkaloglu H, Ucar AR, Dirim AB, Usta Akgul S, Temurhan S, Gok AFK, Ozluk Y, Kilicaslan I, Oguz FS, Sever MS, Aydin AE, and Turkmen A
- Subjects
- Adult, BK Virus, Cytomegalovirus, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Young Adult, Cytomegalovirus Infections etiology, Immunosuppressive Agents adverse effects, Induction Chemotherapy adverse effects, Kidney Transplantation adverse effects, Polyomavirus Infections etiology, Tumor Virus Infections etiology
- Abstract
BACKGROUND Cytomegalovirus (CMV) and BK virus (BKV) are post-transplant opportunistic viral infections that affect patient and graft survival. This study was designed to evaluate the risk of BKV nephropathy and CMV disease in kidney transplant recipients who received induction therapy with ATG or basiliximab. MATERIAL AND METHODS We retrospectively analyzed information on 257 adult patients who underwent kidney transplantation between January 2007 and 2017. Patients were categorized into 3 groups according to the induction therapies. The primary endpoint was the onset of CMV disease or biopsy-confirmed BKV nephropathy. The secondary endpoints were biopsy-proven rejection episodes, graft loss, loss to follow-up, and death. RESULTS We followed 257 patients for a median of 55.5 months. The incidence of CMV disease was significantly higher in the only ATG group compared to the group without induction treatment (p<0.001). There was no significant difference in the incidence of BKV nephropathy among groups (p>0.05). The dosage of ATG (OR, 10.685; 95% CI, 1.343 5 to 85.009; P=0.025) was independent risk factor for death. CONCLUSIONS This study demonstrated that a higher dosage of ATG in high-risk patients is associated with an increased risk of CMV disease and patient death, also, reducing the dosage may be a rational strategy for increasing graft and patient's survival.
- Published
- 2019
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26. Different Courses of Hepatitis B Reinfection After Renal Transplant: A Case Report.
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Yegit O, Demir E, Caliskan Y, Yazici H, and Sever MS
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- Adult, Female, Humans, Male, Middle Aged, Recurrence, Hepatitis B diagnosis, Kidney Failure, Chronic surgery, Kidney Transplantation, Postoperative Complications diagnosis
- Abstract
Hepatitis B surface antigen-positive allografts may be a source of transmission in patients who undergo renal transplantation. Treatment of hepatitis B virus infection with nucleoside/nucleotide analogs in kidney recipients who have hepatitis B virus infection or who have received transplants from hepatitis B surface antigen-positive donors improves long-term patient survival. Antiviral agents are administered as a preemptive or prophylactic therapy at the time of kidney transplantation, rather than as salvage treatment. In this report, we present 2 renal transplant recipients who had hepatitis B virus reinfection or who had developed seroconversion with immunosuppressive treatment. These case reports also demonstrate the unexpectedly different courses of hepatitis B reinfection after kidney transplantation.
- Published
- 2019
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27. Co-Deposition of IgM and C3 May Indicate Unfavorable Renal Outcomes in Adult Patients with Primary Focal Segmental Glomerulosclerosis.
- Author
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Mirioglu S, Caliskan Y, Ozluk Y, Dirim AB, Istemihan Z, Akyildiz A, Yazici H, Turkmen A, Kilicaslan I, and Sever MS
- Subjects
- Adult, Disease Progression, Female, Humans, Male, Risk Factors, Complement C3 metabolism, Glomerulosclerosis, Focal Segmental complications, Glomerulosclerosis, Focal Segmental genetics, Immunoglobulin M metabolism, Kidney pathology
- Abstract
Background/aims: We aimed to investigate the effects of glomerular IgM and C3 deposition on outcomes of adult patients with primary focal segmental glomerulosclerosis (FSGS)., Methods: In this retrospective analysis, 86 consecutive adult patients with biopsy-proven primary FSGS were stratified into 3 groups according to their histopathological features: IgM- C3-, IgM+ C3-, and IgM+ C3+. Primary outcome was defined as at least a 50% reduction in baseline estimated glomerular filtration rate (eGFR) or development of kidney failure, while complete or partial remission rates were secondary outcomes., Results: Glomerular IgM deposits were found in 44 (51.1%) patients, 22 (25.5%) of which presented with accompanying C3 deposition. Patients in IgM+ C3+ group had higher level of proteinuria (5.6 g/24 h [3.77-8.5], p = 0.073), higher percentage of segmental glomerulosclerosis (20% [12.3-27.2], p = 0.001), and lower levels of eGFR (69 ± 37.2 mL/min/1.73 m2, p = 0.029) and serum albumin (2.71 ± 0.85 g/dL, p = 0.045) at the time of diagnosis. Despite 86.3% of patients in IgM+ C3+ group (19/22) received immunosuppressive treatment, the primary outcome was more common in patients in the IgM+ C3+ group compared with patients in IgM+ C3- and IgM- C3- groups (11 [50%] vs. 2 [9%] and 11 [26.1%] respectively [p = 0.010]). Complete or partial remission rates were lower in patients in the IgM+ C3+ group (5/22, 22.7%), as well (p = 0.043). Multivariate Cox regression analysis revealed that IgM and C3 co-deposition was an independent risk factor associated with primary outcome (hazard ratio 3.355, 95% CI 1.349-8.344, p = 0.009)., Conclusions: Glomerular IgM and C3 co-deposition is a predictor of unfavorable renal outcomes in adult patients with primary FSGS., (© 2019 The Author(s) Published by S. Karger AG, Basel.)
- Published
- 2019
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28. Extreme hypercalcemia in a kidney transplant recipient.
- Author
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Demir E, Karaoglan C, Yegen G, Sair B, Yazici H, Turkmen A, and Sever MS
- Subjects
- Aged, Antibodies, Monoclonal, Murine-Derived administration & dosage, Antibodies, Monoclonal, Murine-Derived therapeutic use, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cyclophosphamide administration & dosage, Cyclophosphamide therapeutic use, Doxorubicin administration & dosage, Doxorubicin therapeutic use, Everolimus administration & dosage, Everolimus therapeutic use, Fatal Outcome, Fluorodeoxyglucose F18 administration & dosage, Fluorodeoxyglucose F18 metabolism, Humans, Hypercalcemia blood, Hypercalcemia diagnosis, Hypercalcemia therapy, Lymphoproliferative Disorders diagnostic imaging, Lymphoproliferative Disorders immunology, Male, Positron-Emission Tomography methods, Prednisone administration & dosage, Prednisone therapeutic use, Renal Dialysis methods, Rituximab, Shock, Septic complications, Transplant Recipients, Vincristine administration & dosage, Vincristine therapeutic use, Hypercalcemia etiology, Kidney Transplantation adverse effects, Lymphoproliferative Disorders drug therapy, Lymphoproliferative Disorders pathology
- Abstract
Post-transplant hypercalcemia is a major problem in renal transplant recipients, which may negatively affect both graft and patient survival. In this paper, we present a 66-year-old male kidney transplant recipient, who was admitted to our clinic with symptoms of fever, nausea, vomiting and lethargy. Laboratory data showed good renal function; however, a serum calcium level of 22.1 mg/dL. The patient was treated by isotonic saline together with furosemide and methylprednisolone. Because of treatment resistance, subcutaneous calcitonin and ibandronate were added to the treatment protocol as well. Since all these medications were not effective, hemodialysis with low-calcium (1.25 mmol/L) dialysate was applied for three consecutive days, which resulted in normalization of serum calcium. Several investigations were carried out for diagnosing the underlying etiology. Positron-emission tomography (PET)/CT revealed a strong diffuse uptake of FDG in the bones and spleen. A bone marrow biopsy showed diffuse interstitial infiltration of CD20 + neoplastic B cells and, thus, post transplant lymphoproliferative disease (PTLD) was diagnosed. Tacrolimus was switched to everolimus, mycophenolate mofetil was stopped, while treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) was initiated. Despite all therapeutic interventions, the patient died of septic shock in the intensive care unit on the 10th day of emergency service admission. Importance of hemodialysis as an emergent treatment modality in extreme hypercalcemia, and unfavorable course of PTLD were underlined.
- Published
- 2018
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29. Transplant Patients With Failing Renal Allografts.
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Ucar AR, Demir E, and Sever MS
- Subjects
- Allografts, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents adverse effects, Postoperative Complications etiology, Postoperative Complications mortality, Reoperation, Risk Factors, Time Factors, Treatment Failure, Graft Survival, Kidney Transplantation adverse effects, Nephrectomy adverse effects, Nephrectomy mortality, Postoperative Complications therapy, Renal Dialysis
- Abstract
Progress in patient care and immunosuppressive medications has resulted in improved allograft survival in the early posttransplant period; however, substantial graft loss continues in the long term. Therefore, the number of dialysis patients with failed allografts is increasing progressively. These patients have a worse prognosis than naive dialysis patients. Cardiovascular causes are the leading cause of death, followed by infections and malignancies. Delay in return to dialysis, a chronic inflammatory state, infections, and cancer are contributing factors to mortality, whereas type of dialysis modality does not have a significant effect on outcomes. Graft nephrectomy is a risky operation; therefore, it should not be a routine procedure and rather should be performed only when indicated. Overall, most grafts are left in place, whereas graft nephrectomy is performed in atients with graft intolerance syndrome. Management of immunosuppressive drugs after graft failure is controversial. In the case of maintaining immunosuppression, there is increased risk of infections, cardiovascular diseases, and malignancies and also steroid-related adverse effects. On the other hand, discontinuation of immunosuppressants may result in loss of residual allograft function and also acute graft inflammation. Together, immunosuppressive drugs are almost always discontinued in these patients because of their inherent adverse effects. Considering the sequence of cessation, first antiproliferative drugs are stopped, followed by calcineurin inhibitors, and finally steroids. Because many studies show a clear survival benefit, every attempt should be made for a retransplant in patients with failed renal allografts.
- Published
- 2018
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30. The effect of histopathologic and clinical features on allograft survival in renal transplant patients with antibody-mediated rejection.
- Author
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Akagun T, Yazici H, Caliskan Y, Ozluk Y, Sahin S, Turkmen A, Kılıcaslan I, and Sever MS
- Subjects
- Adult, Biopsy, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Retrospective Studies, Transplantation, Homologous, Turkey, Antibodies blood, Complement C4b immunology, Creatinine blood, Graft Rejection epidemiology, Graft Survival, Kidney Transplantation
- Abstract
Background: Antibody-mediated rejection is a frequent cause of graft failure; however, prognostic indications of this complication have not been well defined. The aim of this study was to evaluate the association of histopathological and clinical features and to determine the effect of these findings on allograft survival in patients with AMR., Methods: Fifty-two patients suffered from AMR (30 male; mean age 39 ± 11 years) were included in the study. Data were investigated retrospectively and graft survival was analyzed. All transplant biopsies were evaluated according to Banff 2009 classification., Results: Of the 52 cases, 45 were transplanted from living-donors. Twenty-one patients were diagnosed in the first 3-months after transplantation. Graft survival was 65% at 12 months and 54% at 36 months. Mean serum creatinine at time of biopsy was 3.8 ± 3.6 mg/dL. Thirty-five of the 52 cases showed diffuse C4d positivity, 12 cases showed focal and 5 remained C4d negative. One of the patients died, 13 experienced graft loss and 38 survived with functioning grafts. Serum creatinine levels at time of biopsy were correlated with graft survival (p = .021: OR = 1.10: 95 % CI = 1.015-1.199). In terms of the impact of pathological findings; tubulitis (p=.007: OR = 2.62: 95 % CI = 1.301-5.276), intimal arteritis (p=.017: OR = 2.85: 95% CI = 1.205-6.744) and interstitial infiltration (p=.004: OR = 3.37: 95% CI = 1.465-7.752) were associated with graft survival., Conclusions: Serum creatinine at time of biopsy, tubulitis, intimal arteritis and interstitial infiltration were significantly associated with graft survival. Antibody-mediated rejection is associated with reduced long-term graft survival.
- Published
- 2017
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31. Re-evaluation of glomerulitis using occlusion criteria based on the Banff 2013 revision: a retrospective study.
- Author
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Ozluk Y, Caliskan Y, Sevinc M, Bayram A, Arikan EA, Turkmen A, Akgul S, Savran FO, Sever MS, and Kilicaslan I
- Subjects
- Adolescent, Adult, Aged, Antibody Specificity, Biopsy, Capillaries pathology, Female, Glomerulonephritis etiology, Glomerulonephritis immunology, Graft Occlusion, Vascular etiology, Graft Occlusion, Vascular immunology, Graft Survival, Humans, Isoantibodies metabolism, Kidney Glomerulus blood supply, Kidney Glomerulus immunology, Kidney Glomerulus pathology, Male, Middle Aged, Observer Variation, Retrospective Studies, Tissue Donors, Young Adult, Glomerulonephritis diagnosis, Graft Occlusion, Vascular diagnosis, Kidney Transplantation adverse effects
- Abstract
The presence of occlusion/near-occlusion of glomerular capillaries was recently added to the existing definition of glomerulitis (g). We retrospectively re-evaluated 135 renal allograft biopsies regarding g to ensure no antibody-damaged grafts were missed. Previous and revised g scores (pg and rg, respectively) were compared for clinicopathologic correlations. The g score did not change in 100 (74.1%) biopsies. Thirty-five (25.9%) biopsies were changed to a lower score. Sensitivity and specificity of pg and rg for the presence of donor-specific antibodies (DSA) were 76% vs. 58% and 70% vs. 79%, respectively. Pg score indicated graft loss with 65% sensitivity and 63% specificity, whereas rg showed 46% sensitivity and 71% specificity. Area under the curve (AUC) values in ROC analysis for DSA and graft loss were as follows: pg, 0.773; rg, 0.693; and pg, 0.635; rg, 0.577, respectively. A comparison of the two AUC values revealed a significant difference between pg and rg only for DSA (P = 0.0076). Pg and post-transplant time of biopsy independently predicted graft loss, whereas rg did not. In conclusion, revised g scores showed lesser sensitivity but higher specificity for DSA and graft loss. Recent definition of g missed antibody-mediated rejection in few cases, and it was not an independent predictor for graft loss., (© 2017 Steunstichting ESOT.)
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- 2017
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32. Hypertensive pulmonary edema related to desmopressin acetate.
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Korkmaz U, Demir E, Yazici H, and Sever MS
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Deamino Arginine Vasopressin adverse effects, Hypertension, Pulmonary chemically induced, Pulmonary Edema chemically induced
- Published
- 2017
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33. Posttransplant Tuberculosis.
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Demir E and Sever MS
- Subjects
- Antitubercular Agents adverse effects, Delayed Diagnosis, Drug Therapy, Combination, Humans, Immunocompromised Host, Immunosuppressive Agents adverse effects, Predictive Value of Tests, Risk Factors, Treatment Outcome, Tuberculosis diagnosis, Tuberculosis immunology, Tuberculosis microbiology, Antitubercular Agents therapeutic use, Organ Transplantation adverse effects, Tuberculosis drug therapy
- Abstract
Tuberculosis is a major problem in the posttransplantation period, because of its high incidence and prevalence, difficulty in diagnosis as well as high risk of morbidity and mortality. In solid-organ transplant recipients, the diagnosis of tuberculosis is complex because it is paucisymptomatic. Tuberculin skin testing results may be negative, and interferon-gamma release assays may be insufficiently sensitive. Furthermore, imaging technique findings are mostly atypical, and sputum smear results can be negative despite the presence of active disease. Therefore, most tuberculosis cases are overlooked, and thus, treatment initiation is often delayed. The treatment of tuberculosis falls under 2 headings: that of active disease and latent disease. The drugs for treating these 2 entities are similar; however, their protocols are completely different. Active disease in the immunocompetent patient is treated mostly by giving isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months (intensive phase), followed by isoniazid and rifampicin for 4 months (continuation phase). The treatment of immunosuppressed patients is controversial; a similar protocol or longer duration of treatment has been suggested as compared to immunocompetent patients. Because there is a drug interaction between antituberculosis drugs (rifamycins) and immunosuppressants (calcineurin/mammalian target of rapamycin inhibitors and glucocorticoids), the risk of graft rejection increases during the treatment of tuberculosis. For the treatment of latent tuberculosis, in regions with a high prevalence of tuberculosis, universal prophylaxis with isoniazid for 6 months (preferably 9 months) has been recommended. In countries where the risk of tuberculosis is lower, no prophylaxis has been proposed. We propose that the best solution is to individualize therapy for patients at greatest risk of the disease. To conclude, posttransplant tuberculosis is still an important source of comorbidity in transplant recipients because of its high frequency, problems in diagnosis and treatment and association with increased risk of morbidity and mortality.
- Published
- 2017
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34. Kidney transplantation due to medical urgency: time for reconsideration?
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Sever MS and Goral S
- Subjects
- Humans, Waiting Lists, Kidney Transplantation, Tissue and Organ Procurement
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- 2016
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35. Dialyzing women and men: does it matter? An observational study.
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Artan AS, Kircelli F, Ok E, Yilmaz M, Asci G, Dogan C, Oto O, Gunestepe K, Basci A, and Sever MS
- Abstract
Background: Application and consequences of hemodialysis treatment may differ between genders; focusing on these differences may be useful to optimize outcomes., Methods: Data from 1 999 648 hemodialysis sessions performed in 10 984 (3316 incident and 7668 prevalent) patients, treated in 55 centers of the European Clinical Database (EuCliD)-Turkey, were analyzed, and various demographic, clinical, biochemical, therapeutic and prognostic parameters were compared., Results: There were 1905 male and 1411 female incident and 4339 male and 3329 female prevalent patients. For females, the mean age in incident (61.8 ± 14.9 years) and prevalent (58.3 ± 15.2 years) patients was higher than for males (60.2 ± 14.8 and 56.5 ± 14.9 years, respectively) (P < 0.001 for both analyses). Also, body mass index was higher, while the hemoglobin level, and the percentage of interdialytic weight gain and arteriovenous fistula were lower. Serum phosphorus was similar in both genders in incident cases, while it was lower in prevalent female patients. Serum parathyroid hormone levels were lower in incident, but higher in prevalent male cases. Erythropoiesis-stimulating agents and vitamin D preparations were more frequently used in female incident and prevalent patients. Hospitalization was more frequent in prevalent females, while it did not differ significantly in the incident cases. Overall, no significant difference was observed in survival rates at 3 years in both incident and prevalent male and female patients., Conclusions: Many parameters differ significantly between female and male dialysis patients. Considering the effects of sex on several parameters may be a valuable approach for achieving better outcomes when formulating treatment strategies in this patient population.
- Published
- 2016
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36. Comparison of Turkish and US haemodialysis patient mortality rates: an observational cohort study.
- Author
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Asci G, Marcelli D, Celtik A, Grassmann A, Gunestepe K, Yaprak M, Tamer AF, Turan MN, Sever MS, and Ok E
- Abstract
Background: There are significant differences between countries in the mortality rates of haemodialysis (HD) patients. The extent of these differences and possible contributing factors are worthy of investigation., Methods: As of March 2009, all patients undergoing HD or haemodiafiltration for >3 months (n = 4041) in the Turkish clinics of the NephroCare network were enrolled. Data were prospectively collected for 2 years through the European Clinical Dialysis Database. Mean age ± standard deviation was 58.7 ± 14.7 years, 45.9% were female and 22.9% were diabetic. Comparison with US data was performed by applying an indirect standardization technique, using specific mortality rates for patients on HD by age, gender, race and primary diagnosis as provided by the 2012 US Renal Data System Annual Data Report as reference., Results: The crude mortality rate in Turkey was 95.1 per 1000 patient-years. Compared with the US reference population, the annual mortality rate for Turkey was significantly lower, irrespective of gender, age and diabetes. After adjustments for age, gender and diabetes, the mortality risk in the Turkish cohort was 50% lower than US whites [95% confidence interval (CI) 0.46-0.54, P < 0.001], 44% lower than US African-Americans (95% CI 0.52-0.61, P < 0.001) and 20% lower than Asian-Americans (95% CI 0.74-0.86, P < 0.05)., Conclusions: The annual mortality rate of prevalent HD patients was found to be significantly lower in the studied Turkish cohort compared with that published by the US Renal Data System Annual Data Report. Differences in practice patterns may contribute to the divergence.
- Published
- 2016
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37. The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients.
- Author
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Massart A, Pallier A, Pascual J, Viklicky O, Budde K, Spasovski G, Klinger M, Sever MS, Sørensen SS, Hadaya K, Oberbauer R, Dudley C, De Fijter JW, Yussim A, Hazzan M, Wekerle T, Berglund D, De Biase C, Pérez-Sáez MJ, Mühlfeld A, Orlando G, Clemente K, Lai Q, Pisani F, Kandus A, Baas M, Bemelman F, Ponikvar JB, Mazouz H, Stratta P, Subra JF, Villemain F, Hoitsma A, Braun L, Cantarell MC, Colak H, Courtney A, Frasca GM, Howse M, Naesens M, Reischig T, Serón D, Seyahi N, Tugmen C, Alonso Hernandez A, Beňa L, Biancone L, Cuna V, Díaz-Corte C, Dufay A, Gaasbeek A, Garnier A, Gatault P, Gentil Govantes MA, Glowacki F, Gross O, Hurault de Ligny B, Huynh-Do U, Janbon B, Jiménez Del Cerro LA, Keller F, La Manna G, Lauzurica R, Le Monies De Sagazan H, Thaiss F, Legendre C, Martin S, Moal MC, Noël C, Pillebout E, Piredda GB, Puga AR, Sulowicz W, Tuglular S, Prokopova M, Chesneau M, Le Moine A, Guérif P, Soulillou JP, Abramowicz M, Giral M, Racapé J, Maggiore U, Brouard S, and Abramowicz D
- Subjects
- Adult, Europe epidemiology, Female, Graft Rejection immunology, Graft Rejection prevention & control, Humans, Incidence, Male, Surveys and Questionnaires, Survival Rate trends, Transplantation, Homologous, Graft Rejection epidemiology, Graft Survival immunology, Immune Tolerance immunology, Immunosuppression Therapy methods, Kidney Transplantation, Transplant Recipients
- Abstract
Background: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time., Methods: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency., Results: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively., Conclusions: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
- Published
- 2016
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38. Acute kidney injury: highlights from the ERA-EDTA Congress in London.
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Sever MS
- Subjects
- Humans, London, Acute Kidney Injury therapy, Congresses as Topic, Nephrology methods, Renal Dialysis
- Abstract
The ERA-EDTA 52nd Congress was held in London, 28-31 May 2015. In the scientific programme, overall, during the symposium, there were 18 lectures, 3 minilectures, 15 free communications and 135 poster presentations on acute kidney injury (AKI). Among many excellent reports and presentations, I selected three hot topics on AKI for the readership of Nephrology Dialysis Transplantation., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
- Published
- 2016
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39. The Clinical Significance of Uric Acid and Complement Activation in the Progression of IgA Nephropathy.
- Author
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Caliskan Y, Ozluk Y, Celik D, Oztop N, Aksoy A, Ucar AS, Yazici H, Kilicaslan I, and Sever MS
- Subjects
- Adolescent, Adult, Aged, Biomarkers blood, Complement Activation physiology, Complement C3, Female, Glomerulonephritis, IGA diagnosis, Humans, Hyperuricemia diagnosis, Male, Middle Aged, Retrospective Studies, Young Adult, Disease Progression, Glomerulonephritis, IGA blood, Hyperuricemia blood, Uric Acid blood
- Abstract
Background/aims: The aim of this study is to investigate the utility of clinical [age, gender, mean arterial pressure (MAP)] and laboratory parameters [eGFR, hemoglobin (Hgb), serum levels of creatinine, uric acid, albumin, proteinuria, hematuria] and also histopathological lesions (Oxford classification parameters, crescents, intensity and pattern of staining for C3, C1Q, IgA, IgG, IgM) as progression markers in patients with IgA Nephropathy (IgAN)., Methods: A total of 111 IgAN patients with a follow-up period >1 year or who reached kidney failure [GFR category G5 chronic kidney disease (CKD)] <1 year were investigated. Primary endpoint was the development of kidney failure or eGFR decline ≥50% from the baseline. Kaplan-Meier and Cox proportional hazards analyses were performed., Results: Mean follow-up period was 33±29 months. Thirty-seven (33.3%) patients progressed to kidney failure and 4 (3.6%) patients developed eGFR decline ≥50% from the baseline after a median of 23 and 65 months, respectively. In multivariate Cox regression analysis, baseline levels of Hgb (HR:0.782, 95% CI 0.559-0.973, p=0.037), serum uric acid (HR:1.293, 95% CI 1.023-1.621, p=0.046), eGFR (HR:0.966, 95% CI 0.947-0.984, p=0.004) and intensity of C3 staining (HR:1.550, 95% CI 1.198-1.976, p=0.049) predicted primary endpoint. Serum uric acid level was associated independently with T score (β=0.303, p=0.005) in patients with eGFR>30 ml/min/m2., Conclusions: Hyperuricemia and the deposition of C3 are independent risk factors for IgAN progression., (© 2016 The Author(s) Published by S. Karger AG, Basel.)
- Published
- 2016
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40. Moderator's view: Pretransplant weight loss in dialysis patients: cum grano salis.
- Author
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Sever MS and Zoccali C
- Subjects
- Exercise, Graft Survival, Humans, Kidney Transplantation, Obesity physiopathology, Renal Dialysis, Renal Insufficiency prevention & control, Weight Loss
- Abstract
A high Body Mass Index (BMI) predicts delayed graft function, all cause and cardiovascular death after transplantation but such risk excess is apparently confined to patients included in studies performed before 2000. Perhaps with the exception of morbid obesity (BMI > 40), clinical outcomes in transplanted obese patients are definitely better than in listed dialysis patients who don't receive a renal transplant. Furthermore the new Scientific Registry of Transplant Recipients (SRTR) risk calculator incorporates BMI into the prediction model of the global risk for the graft's and patient's survival appropriately framing the risk of obesity in a multidimensional risk context. In the aggregate, available knowledge suggests that clinical decisions on weight loss before transplantation should be context specific. Renal transplant patients from living donors have substantial better survival in comparison to well matched dialysis patients listed for the same intervention at all BMI categories. Therefore renal transplantation in obese patients with a living donor may be prioritized. The attitude of fully informed obese patients at accepting the risk driven by transplantation, the experience of the surgical team with obese patients (including also robotic surgery) are of obvious importance. Renal transplantation should be timely considered when reasonable attempts at weight loss failed or appear overtly unrealistic. Transplantation in morbidly obese patients with BMI > 40, a category where the survival advantage of transplantation vs dialysis is probably small and still uncertain, particularly so in African-Americans, should be deferred until significant weight loss is achieved., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)
- Published
- 2015
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41. Disaster nephrology: a new concept for an old problem.
- Author
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Sever MS, Lameire N, Van Biesen W, and Vanholder R
- Abstract
Natural and man-made mass disasters directly or indirectly affect huge populations, who need basic infrastructural help and support to survive. However, despite the potentially negative impact on survival chances, these health care issues are often neglected by the authorities. Treatment of both acute and chronic kidney diseases (CKDs) is especially problematic after disasters, because they almost always require complex technology and equipment, whereas specific drugs may be difficult to acquire for the treatment of the chronic kidney patients. Since many crush victims in spite of being rescued alive from under the rubble die afterward due to lack of dialysis possibilities, the terminology of 'renal disaster' was introduced after the Armenian earthquake. It should be remembered that apart from crush syndrome, multiple aetiologies of acute kidney injury (AKI) may be at play in disaster circumstances. The term 'seismonephrology' (or earthquake nephrology) was introduced to describe the need to treat not only a large number of AKI cases, but the management of patients with CKD not yet on renal replacement, as well as of patients on haemodialysis or peritoneal dialysis and transplanted patients. This wording was later replaced by 'disaster nephrology', because besides earthquakes, many other disasters such as hurricanes, tsunamis or wars may have a negative impact on the ultimate outcome of kidney patients. Disaster nephrology describes the handling of the many medical and logistic problems in treating kidney patients in difficult circumstances and also to avoid post-disaster chaos, which can be made possible by preparing medical and logistic scenarios. Learning and applying the basic principles of disaster nephrology is vital to minimize the risk of death both in AKI and CKD patients.
- Published
- 2015
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42. Disaster nephrology: crush injury and beyond.
- Author
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Gibney RT, Sever MS, and Vanholder RC
- Subjects
- Acute Kidney Injury diagnosis, Acute Kidney Injury mortality, Acute Kidney Injury physiopathology, Crush Syndrome diagnosis, Crush Syndrome mortality, Crush Syndrome physiopathology, Delivery of Health Care, Integrated, Emergencies, Humans, Mass Casualty Incidents, Nephrology organization & administration, Renal Insufficiency, Chronic diagnosis, Renal Insufficiency, Chronic mortality, Renal Insufficiency, Chronic physiopathology, Risk Factors, Time Factors, Treatment Outcome, Acute Kidney Injury prevention & control, Crush Syndrome therapy, Disaster Planning organization & administration, Fluid Therapy, Health Services Accessibility organization & administration, Nephrology methods, Renal Dialysis, Renal Insufficiency, Chronic therapy
- Abstract
Disasters result in a substantial number of renal challenges, either by the creation of crush injury in victims trapped in collapsed buildings or by the destruction of existing dialysis facilities, leaving chronic dialysis patients without access to their dialysis units, medications, or medical care. Over the past two decades, lessons have been learned from the response to a number of major natural disasters that have impacted significantly on crush-related acute kidney injury and chronic dialysis patients. In this paper we review the pathophysiology and treatment of the crush syndrome, as summarized in recent clinical recommendations for the management of crush syndrome. The importance of early fluid resuscitation in preventing acute kidney injury is stressed, logistic difficulties in disaster conditions are described, and the need for an implementation of a renal disaster relief preparedness program is underlined. The role of the Renal Disaster Relief Task Force in providing emergency disaster relief and the logistical support required is outlined. In addition, the importance of detailed education of chronic dialysis patients and renal unit staff in the advance planning for such disasters and the impact of displacement by disasters of chronic dialysis patients are discussed.
- Published
- 2014
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43. Transplantation-steroid-impaired glucose metabolism: a hope for improvement?
- Author
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Sever MS
- Subjects
- Blood Glucose, Carbohydrate Metabolism drug effects, Humans, Hyperglycemia prevention & control, Immunosuppressive Agents therapeutic use, Kidney Transplantation, Prednisolone therapeutic use, Glucose metabolism, Hyperglycemia chemically induced, Immunosuppressive Agents adverse effects, Prednisolone adverse effects
- Published
- 2014
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44. The Effects of Helicobacter pylori Eradication on Proteinuria in Patients with Primary Glomerulonephritis.
- Author
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Caliskan B, Yazici H, Caliskan Y, Ozluk Y, Gulluoglu M, Kilicaslan I, Turkmen A, and Sever MS
- Abstract
Background. Membranous nephropathy (MN) is a common cause of nephrotic syndrome. In most cases it is idiopathic, while it may also be secondary to many diseases. In this study, prevalence of H. pylori infection and the effects of H. pylori eradication on proteinuria levels were investigated. Methods. Thirty five patients with MN (19 male), 12 patients with IgA nephropathy (4 male) and 12 patients with focal segmental glomerulosclerosis (FSGS) (8 male) were studied. The presence of H. pylori antigen was investigated in renal tissues obtained by biopsy, and the effects of H. pylori eradication on proteinuria levels were investigated. Results. Immunohistochemistry with H. pylori antigen revealed no positive staining in the glomeruli of all patients. 19 patients (54%) with MN, 10 (83%) with IgA nephropathy and 4 (33%) with FSGS were positive for H. pylori stool antigen test (P = 0.045). Patients with H. pylori infection were administered eradication therapy (lansoprazole, 30 mg twice daily, plus amoxicillin, 0.75 g twice daily, plus clarithromycin, 250 mg twice daily, for 14 days). Before the eradication therapy the mean proteinuria of patients with MN, IgA nephropathy and FSGS were 2.42 ± 3.24 g/day, 2.12 ± 1.63 g/day and 1.80 ± 1.32 g/day, respectively. Three months after eradication, baseline proteinuria levels of patients with MN significantly decreased to 1.26 ± 1.73 g/day (P = 0.031). In all three groups there were no significant differences with regard to serum creatinine, albumin and C-reactive protein levels before and after eradication therapy. Conclusions. The eradication of H. pylori infection may be effective to reduce proteinuria in patients with MN, while spontaneous remission of MN could not be excluded in this patient cohort. This trial is registered with NCT00983034.
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- 2014
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45. Management of crush victims in mass disasters: highlights from recently published recommendations.
- Author
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Sever MS and Vanholder R
- Subjects
- Decision Trees, Humans, Practice Guidelines as Topic, Crush Syndrome therapy, Disasters
- Abstract
Crush syndrome is the second most common cause of death after earthquakes (the first most common is direct trauma). Many logistic problems with the treatment of patients with crush syndrome are due to chaotic disaster circumstances; consequently, medical and logistic recommendations on the treatment of crush victims are needed. In a joint initiative of the Renal Disaster Relief Task Force of the International Society of Nephrology and European Renal Best Practice, a work group of nephrologists, intensivists, surgeons, and logisticians with disaster experience or experts in guideline preparation collaborated to provide comprehensive information and recommendations on the management of crush casualties considering their occurrence with "epidemic" dimensions after mass disasters. The result is the monograph "Recommendations for the Management of Crush Victims in Mass Disasters", which may help provide effective health care to disaster victims with renal problems. This article discusses medical and logistic principles of the treatment of crush victims, both at the disaster field and on admission to hospitals, and guidance is described. The importance of early fluid administration even before extrication of the victims and avoidance of potassium-containing solutions during the treatment of crush victims is underlined. Also, the logistic problems in treating crush casualties are emphasized. The most important aspects of the recently published recommendations are highlighted.
- Published
- 2013
- Full Text
- View/download PDF
46. Crush recommendations: a step forward in disaster nephrology.
- Author
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Vanholder R and Sever MS
- Subjects
- Humans, Crush Syndrome pathology, Crush Syndrome therapy, Disasters
- Published
- 2012
- Full Text
- View/download PDF
47. Recommendation for the management of crush victims in mass disasters.
- Author
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Sever MS and Vanholder R
- Subjects
- Disease Management, Evidence-Based Medicine, Humans, Crush Syndrome pathology, Crush Syndrome therapy, Disasters
- Abstract
"Recommendations for the management of crush victims in mass disasters" aims to assist medics, paramedics and rescue team members who provide care during disasters. Development of the recommendations followed an explicit process of literature review and, also internet and face-to-face discussions. The chapters cover medical and logistic measures, to be taken both at the disaster field and in the hospitals, to cope with the problems created by a catastrophe. Recommendations were based on retrospective analyses and case reports on past disasters, and also expert judgment or opinion. Since there are no randomized controlled trials, no GRADE approach was used to develop the recommendations, and no strengths of recommendations or levels of evidence are provided.
- Published
- 2012
- Full Text
- View/download PDF
48. Management of crush syndrome casualties after disasters.
- Author
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Sever MS and Vanholder R
- Abstract
After direct impact of the trauma, crush syndrome is the second most frequent cause of death after mass disasters. However, since crush syndrome is quite rare in daily practice, mistakes are frequent in the treatment of these cases. This paper summarizes the etiopathogenesis of traumatic rhabdomyolysis and of crush syndrome-based acute kidney injury. The clinical and laboratory features, prophylaxis, and treatment of crush cases are described as well. The importance of early and energetic fluid resuscitation is underlined for prophylaxis of acute kidney injury. Since there is chaos, and an overwhelming number of victims, logistic drawbacks create a specific problem in the treatment of crush victims after mass disasters. Potential solutions for logistic hurdles and disaster preparedness scenarios have also been provided in this review article.
- Published
- 2011
- Full Text
- View/download PDF
49. Application of the RIFLE criteria in patients with crush-related acute kidney injury after mass disasters.
- Author
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Sever MS, Kellum J, Hoste E, and Vanholder R
- Subjects
- Acute Kidney Injury etiology, Adult, Aged, Humans, Kidney Failure, Chronic etiology, Middle Aged, Prognosis, Renal Insufficiency etiology, Retrospective Studies, Risk Factors, Severity of Illness Index, Young Adult, Acute Kidney Injury diagnosis, Crush Syndrome complications, Disasters
- Abstract
Background: The term acute kidney injury (AKI) and its classification in strata defined as Risk, Injury, Failure, Loss and End-stage renal failure (RIFLE) need to be validated in different patient groups. RIFLE may be useful to foresee medical and logistic problems in crush-related AKI in disaster victims., Methods: Taken from the Marmara earthquake crush database, the subjects included 416 patients who were categorized according to the modified RIFLE criteria and 18 victims with crush injury but with normal serum creatinine who served as controls. Associations between each RIFLE category and various parameters were investigated., Results: There were 27, 79 and 310 patients in the risk, injury and failure groups, respectively. Urine volume and serum albumin were lower; blood pressure, blood urea nitrogen, serum uric acid, potassium and phosphorus were higher; oliguric and polyuric periods were longer; medical complications were more frequent; and number of transfusions, dialysis sessions and days of dialysis support were higher in more severe AKI categories. Glomerular filtration rate at discharge was progressively lower in proportion to the severity of RIFLE classification. However, survival outcome did not differ among controls and patients who suffered from AKI nor in between RIFLE categories., Conclusions: In disaster crush victims, RIFLE classification can be useful to foresee the medical complications, need for therapeutic interventions and logistic support and also renal function at discharge though, perhaps, not survival.
- Published
- 2011
- Full Text
- View/download PDF
50. Endogenous testosterone and mortality in male hemodialysis patients: is it the result of aging?
- Author
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Gungor O, Kircelli F, Carrero JJ, Asci G, Toz H, Tatar E, Hur E, Sever MS, Arinsoy T, and Ok E
- Subjects
- Adult, Age Factors, Aged, Biomarkers blood, Cardiovascular Diseases blood, Cardiovascular Diseases mortality, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Humans, Kaplan-Meier Estimate, Kidney Diseases blood, Kidney Diseases complications, Kidney Diseases mortality, Linear Models, Logistic Models, Male, Middle Aged, Proportional Hazards Models, Risk Assessment, Risk Factors, Testosterone blood, Time Factors, Treatment Outcome, Turkey epidemiology, Aging blood, Cardiovascular Diseases etiology, Kidney Diseases therapy, Renal Dialysis mortality, Testosterone deficiency
- Abstract
Background and Objectives: Low serum testosterone levels in hemodialysis (HD) patients have recently been associated with cardiovascular risk factors and increased mortality. To confirm this observation, we investigated the predictive role of serum total testosterone levels on mortality in a large group of male HD patients from Turkey., Design, Settings, Participants, & Measurements: A total of 420 prevalent male HD patients were sampled in March 2005 and followed up for all-cause mortality. Serum total testosterone levels were measured by ELISA at baseline and studied in relation to mortality and cardiovascular risk profile., Results: Mean testosterone level was 8.69 ± 4.10 (0.17 to 27.40) nmol/L. A large proportion of patients (66%) had testosterone deficiency (<10 nmol/L). In univariate analysis, serum testosterone levels were positively correlated with creatinine and inversely correlated with age, body mass index, and lipid parameters. During an average follow-up of 32 months, 104 (24.8%) patients died. The overall survival rate was significantly lower in patients within the low testosterone tertile (<6.8 nmol/L) compared with those within the high tertile (>10.1 nmol/L; 64 versus 81%; P = 0.004). A 1-nmol/L increase in serum testosterone level was associated with a 7% decrease in overall mortality (hazard ratio 0.93; 95% confidence interval 0.89 to 0.98; P = 0.01); however, this association was dependent on age and other risk factors in adjusted Cox regression analyses., Conclusions: Testosterone deficiency is common in male HD patients. Although testosterone levels, per se, predicted mortality in this population, this association was largely dependent on age.
- Published
- 2010
- Full Text
- View/download PDF
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