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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

Annick Massart 1, 2, * Annaïck Pallier 3 Julio Pascual 4 Ondrej Viklicky 5 Klemens Budde 6 Goce Spasovski 7 Marian Klinger 8 Mehmet Sever 9 Søren Schwartz Sørensen 10 Karine Hadaya 11 Rainer Oberbauer 12 Christopher Dudley 13 Johan de Fijter 14 Alexander Yussim 15 Marc Hazzan 16 Thomas Wekerle 17 David Berglund 18 Consuelo de Biase 19 María José Pérez-Sáez 4 Anja Mühlfeld 20 Giuseppe Orlando 21 Katia Clemente 22 Quirino Lai 22 Francesco Pisani 22 Aljosa Kandus 23 Marije Baas 24 Frederike Bemelman 25 Jadranka Buturovic Ponikvar 23 Hakim Mazouz 26 Piero Stratta 27 Jean-François Subra 28 Florence Villemain 28 Andries Hoitsma 24 Laura Braun 29 Maria Cantarell 30 Hulya Colak 31 Aisling Courtney 32 Giovanni Frasca 33 Matthew Howse 34 Maarten Naesens 35 Tomas Reischig 36 Daniel Serón 30 Nurhan Seyahi 37 Cem Tugmen 38 Angel Alonso Hernandez 39 Luboslav Beňa 40 Luigi Biancone 41 Vania Cuna 42, 43 Carmen Díaz-Corte 44 Alexandre Dufay 45 André Gaasbeek 46 Arnaud Garnier 47 Philippe Gatault 48 Miguel Govantes 49 François Glowacki 50 Oliver Gross 51 Bruno Hurault de Ligny 52 Uyen Huynh-Do 53 Bénédicte Janbon 54 Luis Antonio Jiménez del Cerro 55 Frieder Keller 56 Gaetano Manna 43 Ricardo Lauzurica 57 Hervé de Sagazan 45 Friedrich Thaiss 58 Christophe Legendre 59, 60 Séverine Martin 61 Marie-Christine Moal 62 Christian Noël 50 Evangeline Pillebout 63 Gian Piredda 64 Ana Puga 65 Wladyslaw Sulowicz 66 Serhan Tuglular 67 Michaela Prokopova 5 Mélanie Chesneau 68 Alain Le Moine 69 Pierrick Guérif 68 Jean-Paul Soulillou 3, 68 Marc Abramowicz 70 Magali Giral 3, 68 Judith Racapé 71 Umberto Maggiore 19 Sophie Brouard 3, 68 Daniel Abramowicz 72
* Corresponding author
1 ULB - Renal Unit [Brussels, Belgium]
2 Medical Genetics Department [Brussels, Belgium]
3 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
4 Hospital del Mar - Nephrology [Barcelona, Spain]
5 Transplant Center - Department of Nephrology [Prague, Czech Republic]
6 Department of Nephrology [Berlin, Germany]
7 Department of Nephrology [Skopje, Macedonia]
8 Nephrology and Transplantation Medicine [Wrocław, Poland]
9 Internal Medicine, Nephrology [Istanbul, Turkey]
10 Nephrology P [Copenhagen, Denmark]
11 Nephrology and Transplantation [Geneva, Switzerland]
12 Department of Medicine III–Nephrology, Hypertension and Renal Transplantation [Linz, Austria]
13 Richard Bright Renal Centre [Bristol, UK]
14 Department of Nephrology [Leiden, The Netherlands]
15 Rabin Medical Center - Department of Transplantation [Tel Aviv, Israël]
16 Département de Néphrologie [CHRU Lille]
17 Section of Transplantation Immunology - Department of Surgery [Vienna, Austria]
18 Department of Immunology, Genetics and Pathology - Section of Clinical Immunology [Uppsala, Sweden]
19 Centro Trapianti di Parma - UOS Trapianti Rene Pancreas [Parma, Italy]
20 Department of Nephrology [Aachen, Germany]
21 Department of Surgery - Section of Transplantation [Winston-Salem, NC, USA]
22 U.O.C. Trapianti D’Organo [L’Aquila, Italy]
23 Renal Transplantation Centre Ljubljana - Department of Nephrology [Ljubljana, Slovenia]
24 Kidney Diseases [Nijmegen, The Netherlands]
25 Department of Nephrology - Renal Transplant Unit [Amsterdam, The Netherlands]
26 Service de Néphrologie - Unité de Transplantation Rénale et Pancréatique [CHU Sud, Amiens]
27 Department of Translational Medicine [Novara, Italy]
28 Service de Néphrologie-Dialyse-Transplantation [Angers]
29 Hôpital de jour de Néphrologie - service de Néphrologie et Transplantation Rénale [CHU Strasbourg]
30 Vall d’Hebron Hospital - Pediatric Nephrology [Barcelona, Spain]
31 Department of Nephrology [Izmir, Turkey]
32 Regional Nephrology Unit [Belfast, UK]
33 Nefrologia, Dialisi e Trapianto di rene [Ancona, Italy]
34 Nephrology/Transplantation [Liverpool, UK]
35 Department of Nephrology and Renal Transplantation [Leuven, Belgium]
36 Department of Internal Medicine - Nephrology Ward [Pilsen, Czech Republic]
37 Istanbul University
38 Tepecik Training and Research Hospital [Izmir, Turkey]
39 Servicio de Nefrología
40 Transplant Centre
41 University of Turin
42 St. Orsola University Hospital
43 University of Bologna
44 HUCA - Hospital Universitario Central de Asturias
45 Service Néphrologie [Roubaix]
46 Leids Universitair Medisch Centrum [Leiden, The Netherlands]
47 Néphrologie - Médecine Interne - Hypertension Pédiatrique,
48 Service Néphrologie - Immunoclinique [CHRU Tours]
49 Hospital Universitario Virgen del Rocío [Sevilla]
50 Service de Néphrologie et Transplantation rénale [CHRU-lille]
51 University Medicine Göttingen
52 Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen]
53 University Hospital Bern - University of Bern [Bern, Switzerland]
54 Transplantation rénale [CHU Grenoble]
55 Hospital General Universitario de Alicante
56 Universitätsklinikum Ulm - University Hospital of Ulm
57 Hospital Universitario Germans Trias I Pujol
58 University Hospital Hamburg-Eppendorf
59 UPD5 - Université Paris Descartes - Paris 5
60 CHU Necker - Enfants Malades [AP-HP]
61 Service d'hémodialyse et de Néphrologie [Libourne]
62 CHRU - Service de néphrologie, dialyse et transplantation rénale
63 Département de Néphrologie et transplantation [Hôpital Saint Louis - APHP]
64 Kidney Transplant Az. Osp. G. Brotzu
65 Hospital Universitario Insular de Gran Canaria
66 University Hospital in Krakow
67 Marmara School of Medicine Hastanesi
68 Institute of Transplantation Urology and Nephrology [CHU Nantes]
69 ULB - Université libre de Bruxelles
70 Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire
71 Research Center of Epidemiology, Biostatistics and Clinical Research,
72 Nephrology-Renal Transplantation Department
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.
Keywords : operational tolerance graft survival frequency kidney transplantation minimally immunosuppressed patients
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INSERM | UNAM | UNIV-PARIS5 | UNIV-NANTES | CRTI | UNIV-ANGERS | USPC | COMUE-NORMANDIE | UNICAEN | UNIV-PARIS

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Annick Massart, Annaïck Pallier, Julio Pascual, Ondrej Viklicky, Klemens Budde, et al.. The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients. Nephrology Dialysis Transplantation, Oxford University Press (OUP), 2016, 31 (6), pp.1002-1013. ⟨10.1093/ndt/gfv437⟩. ⟨inserm-02153251⟩

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