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The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients

A. Massart, A. Pallier, J. Pascual, O. Viklicky, K. Budde, G. Spasovski, M. Klinger, MS. Sever, SS. Sørensen, K. Hadaya, R. Oberbauer, C. Dudley, JW. De Fijter, A. Yussim, M. Hazzan, T. Wekerle, D. Berglund, C. De Biase, MJ. Pérez-Sáez, A....

. 2016 ; 31 (6) : 1002-13. [pub] 20160112

Language English Country England, Great Britain

Document type Journal Article, Multicenter Study

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.

Department of Immunology Genetics and Pathology Section of Clinical Immunology Uppsala University Sweden

Department of Medical Sciences University of Turin Turin Italy

Department of Medicine 3 Nephrology Hypertension and Renal Transplantation Krankenhaus Elisabethinen Linz Linz Austria

Department of Medicine Division of Nephrology Leiden University Medical Center Leiden The Netherlands

Department of Nephrology and Renal Transplantation University Hospitals Leuven Leuven Belgium

Department of Nephrology and Rheumatology University Medicine Göttingen Göttingen Germany

Department of Nephrology Institute for Clinical and Experimental Medicine Prague Czech Republic

Department of Nephrology Renal Transplantation Centre Ljubljana University Medical Centre Ljubljana Ljubljana Slovenia

Department of Nephrology University Hospital Aachen Aachen Germany

Department of Nephrology University Hospital Krakow Krakow Poland

Department of Specialized Experimental and Diagnostic Medicine Section of Nephrology Nephrology Dialysis and Renal Transplant Unit St Orsola University Hospital University of Bologna Bologna Italy

Department of Translational Medicine Amedeo Avogadro University AOU Maggiore della Carità di Novara Novara Italy

Department of Transplantation Rabin Medical Center Tel Aviv University Sackler School of Medicine Tel Aviv Israël

Division of Nephrology Hypertension and Clinical Pharmacology Inselspital University Hospital Bern Bern Switzerland

General Surgery Tepecik Training and Research Hospital Yenisehir Izmir Turkey

Hôpital de jour de Néphrologie service de Néphrologie et Transplantation Rénale Nouvel hôpital Civil CHU de Strasbourg Strasbourg France

Institute of Transplantation Urology and Nephrology Nantes University Hospital Nantes France

Internal Medicine 1 Nephrology University Hospital Ulm Ulm Germany

Internal Medicine Nephrology Istanbul School of Medicine Istanbul Turkey

Joint Research Unit 1064 French Institute of Health and Medical Research Nantes France

Joint Research Unit 1064 French Institute of Health and Medical Research Nantes France Institute of Transplantation Urology and Nephrology Nantes University Hospital Nantes France Faculty of Medicine Nantes University Nantes France

Kidney Diseases Kidney Transplant Az Osp G Brotzu Cagliari Italy

Kidney Diseases Radboudumc Nijmegen Nijmegen The Netherlands

Medical Genetics Department and IRIBHM ULB Brussels Belgium

Nefrologia Dialisi e Trapianto di rene AO Torrette Umberto 1 Ancona Italy

Néphrologie Médecine Interne Hypertension Pédiatrique Hôpital des Enfants Toulouse France

Nephrology and Transplantation Geneva University Hospitals Geneva Switzerland

Nephrology and Transplantation Medicine Wrocław Poland

Nephrology Charité Campus Mitte Berlin Germany

Nephrology Department CHU Lille Lille France

Nephrology Department University Hospital of Lille Lille France

Nephrology Hospital del Mar Barcelona Spain

Nephrology Hospital Germans Trias i Pujol Badalona Spain

Nephrology Hospital Universitari Val d'Hebron Barcelona Spain

Nephrology Hospital Universitario Central de Asturias Oviedo Spain

Nephrology Istanbul University Cerrahpasa Medical Faculty Istanbul Turkey

Nephrology Marmara School of Medicine Hastanesi Istanbul Turkey

Nephrology P Rigshospitalet Copenhagen Denmark

Nephrology Renal Transplantation Department Universitair Ziekenhuis Antwerp Antwerp Belgium Université Libre de Bruxelles Brussels Belgium

Nephrology Tepecik Training and Research Hospital Izmir Turkey

Nephrology Transplantation Royal Liverpool University Hospital Liverpool UK

Nephrology Unit Hôpital Saint Louis Paris France

Nephrology Ward Department of Internal Medicine University Hospital Pilsen Pilsen Czech Republic

Nierziekten LUMC Leiden The Netherlands

Regional Nephrology Unit Belfast City Hospital Belfast UK

Renal Transplant Unit Department of Nephrology Academic Medical Center Amsterdam The Netherlands

Renal Unit CUB Hôpital Erasme Université Libre de Bruxelles Brussels Belgium

Renal Unit CUB Hôpital Erasme Université Libre de Bruxelles Brussels Belgium Medical Genetics Department ULB Brussels Belgium

Research Center of Epidemiology Biostatistics and Clinical Research School of Public Health ULB Brussels Belgium

Richard Bright Renal Centre Southmead Hospital North Bristol NHS Trust Bristol UK

Section of Transplantation Immunology Department of Surgery Medical University of Vienna Vienna Austria

Service d'hémodialyse et de Néphrologie Hôpital Robert Boulin Libourne France

Service de Néphrologie CHRU Avenue Georges Clémenceau Caen France

Service de Néphrologie CHRU de Brest Brest France

Service de Néphrologie Dialyse Transplantation CHU Angers Angers France

Service de Néphrologie Unité de Transplantation Rénale et Pancréatique CHU Sud Amiens France

Service Néphrologie Hôpital Victor Provo Roubaix France

Service Néphrologie Immunoclinique CHRU Hôpital Bretonneau Tours France

Servicio de Nefrología Hospital General Universitario de Alicante Alicante Spain

Servicio de Nefrología Hospital Universitario A Coruña Spain

Servicio de Nefrología Hospital Universitario Insular de Gran Canaria Las Palmas de Gran Canaria Spain

Transplant Centre University Hospital Louis Pasteur Kosice Kosice Slovakia

Transplantation rénale CHU Grenoble Grenoble France

U O C Trapianti D'Organo L'Aquila Italy

Unidad de Gestión Clínica de Urología y Nefrología Hospital Universitario Virgen del Rocío Sevilla Spain

Université Paris Descartes et Hôpital Necker Paris France

University Department of Nephrology Skopje Macedonia

University Hospital Hamburg Eppendorf Hamburg Germany

UOS Trapianti Rene Pancreas Centro Trapianti di Parma Az Ospedaliero Universitaria di Parma Parma Italy

Wake Forest School of Medicine Department of Surgery Section of Transplantation Winston Salem NC USA

References provided by Crossref.org

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$a BACKGROUND: Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. METHODS: Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many 'operationally tolerant' patients (TOL; defined as having a serum creatinine <1.7 mg/dL and proteinuria <1 g/day or g/g creatinine despite at least 1 year without any immunosuppressive drug) and 'almost tolerant' patients (minimally immunosuppressed patients (MIS) receiving low-dose steroids) as possible. We reported their number and the total number of kidney transplants performed at each centre to calculate their frequency. RESULTS: One hundred and forty-seven questionnaires were returned and we identified 66 TOL (61 with complete data) and 34 MIS patients. Of the 61 TOL patients, 26 were previously described by the Nantes group and 35 new patients are presented here. Most of them were noncompliant patients. At data collection, 31/35 patients were alive and 22/31 still operationally tolerant. For the remaining 9/31, 2 were restarted on immunosuppressive drugs and 7 had rising creatinine of whom 3 resumed dialysis. Considering all patients, 10-year death-censored graft survival post-immunosuppression weaning reached 85% in TOL patients and 100% in MIS patients. With 218 913 kidney recipients surveyed, cumulative incidences of operational tolerance and almost tolerance were estimated at 3 and 1.5 per 10 000 kidney recipients, respectively. CONCLUSIONS: In kidney transplantation, operational tolerance and almost tolerance are infrequent findings associated with excellent long-term death-censored graft survival.
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$a Mazouz, Hakim $u Service de Néphrologie, Unité de Transplantation Rénale et Pancréatique, CHU Sud, Amiens, France.
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$a Stratta, Piero $u Department of Translational Medicine, Amedeo Avogadro University, AOU Maggiore della Carità di Novara, Novara, Italy.
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$a Subra, Jean-François $u Service de Néphrologie-Dialyse-Transplantation, CHU Angers, Angers, France.
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$a Colak, Hulya $u Nephrology, Tepecik Training and Research Hospital, Izmir, Turkey.
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$a Courtney, Aisling $u Regional Nephrology Unit, Belfast City Hospital, Belfast, UK.
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$a Frasca, Giovanni Maria $u Nefrologia, Dialisi e Trapianto di rene, AO Torrette Umberto I, Ancona, Italy.
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$a Howse, Matthew $u Nephrology/Transplantation, Royal Liverpool University Hospital, Liverpool, UK.
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$a Naesens, Maarten $u Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium.
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$a Alonso Hernandez, Angel $u Servicio de Nefrología, Hospital Universitario, A Coruña, Spain. $7 gn_A_00004707
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$a Biancone, Luigi $u Department of Medical Sciences, University of Turin, Turin, Italy.
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$a Gentil Govantes, Miguel Angel $u Unidad de Gestión Clínica de Urología y Nefrología, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
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$a Glowacki, François $u Nephrology Department, University Hospital of Lille, Lille, France.
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$a Gross, Oliver $u Department of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany.
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$a Hurault de Ligny, Bruno $u Service de Néphrologie, CHRU Avenue Georges Clémenceau, Caen, France.
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$a Huynh-Do, Uyen $u Division of Nephrology, Hypertension and Clinical Pharmacology, Inselspital, University Hospital Bern, Bern, Switzerland.
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$a Janbon, Bénédicte $u Transplantation rénale, CHU Grenoble, Grenoble, France.
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$a Jiménez Del Cerro, Luis Antonio $u Servicio de Nefrología, Hospital General Universitario de Alicante, Alicante, Spain.
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$a Keller, Frieder $u Internal Medicine 1, Nephrology, University Hospital Ulm, Ulm, Germany.
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$a Thaiss, Friedrich $u University Hospital Hamburg Eppendorf (UKE), Hamburg, Germany.
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$a Legendre, Christophe $u Université Paris Descartes et Hôpital Necker, Paris, France.
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$a Martin, Séverine $u Service d'hémodialyse et de Néphrologie, Hôpital Robert Boulin, Libourne, France.
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$a Piredda, Gian Benedetto $u Kidney Diseases, Kidney Transplant Az. Osp. G. Brotzu, Cagliari, Italy.
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$a Puga, Ana Ramírez $u Servicio de Nefrología, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain.
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$a Sulowicz, Wladyslaw $u Department of Nephrology, University Hospital Krakow, Krakow, Poland.
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$a Soulillou, Jean-Paul $u Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France Faculty of Medicine, Nantes University, Nantes, France.
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$a Abramowicz, Marc $u Medical Genetics Department and IRIBHM (Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire), ULB, Brussels, Belgium.
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$a Giral, Magali $u Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France Faculty of Medicine, Nantes University, Nantes, France.
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$a Racapé, Judith $u Research Center of Epidemiology, Biostatistics and Clinical Research, School of Public Health, ULB, Brussels, Belgium.
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$a Maggiore, Umberto $u UOS Trapianti Rene Pancreas, Centro Trapianti di Parma, Az. Ospedaliero-Universitaria di Parma, Parma, Italy.
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$a Brouard, Sophie $u Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France Faculty of Medicine, Nantes University, Nantes, France.
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$a Abramowicz, Daniel $u Nephrology-Renal Transplantation Department, Universitair Ziekenhuis Antwerp, Antwerp, Belgium Université Libre de Bruxelles (ULB), Brussels, Belgium.
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