Annick Massart1, Annaïck Pallier2, Julio Pascual3, Ondrej Viklicky4, Klemens Budde5, Goce Spasovski6, Marian Klinger7, Mehmet Sukru Sever8, Søren Schwartz Sørensen9, Karine Hadaya10, Rainer Oberbauer11, Christopher Dudley12, Johan W De Fijter13, Alexander Yussim14, Marc Hazzan15, Thomas Wekerle16, David Berglund17, Consuelo De Biase18, María José Pérez-Sáez3, Anja Mühlfeld19, Giuseppe Orlando20, Katia Clemente21, Quirino Lai21, Francesco Pisani21, Aljosa Kandus22, Marije Baas23, Frederike Bemelman24, Jadranka Buturovic Ponikvar22, Hakim Mazouz25, Piero Stratta26, Jean-François Subra27, Florence Villemain27, Andries Hoitsma23, Laura Braun28, Maria Carmen Cantarell29, Hulya Colak30, Aisling Courtney31, Giovanni Maria Frasca32, Matthew Howse33, Maarten Naesens34, Tomas Reischig35, Daniel Serón29, Nurhan Seyahi36, Cem Tugmen37, Angel Alonso Hernandez38, Luboslav Beňa39, Luigi Biancone40, Vania Cuna41, Carmen Díaz-Corte42, Alexandre Dufay43, André Gaasbeek44, Arnaud Garnier45, Philippe Gatault46, Miguel Angel Gentil Govantes47, François Glowacki48, Oliver Gross49, Bruno Hurault de Ligny50, Uyen Huynh-Do51, Bénédicte Janbon52, Luis Antonio Jiménez Del Cerro53, Frieder Keller54, Gaetano La Manna41, Ricardo Lauzurica55, Hervé Le Monies De Sagazan43, Friedrich Thaiss56, Christophe Legendre57, Séverine Martin58, Marie-Christine Moal59, Christian Noël48, Evangeline Pillebout60, Gian Benedetto Piredda61, Ana Ramírez Puga62, Wladyslaw Sulowicz63, Serhan Tuglular64, Michaela Prokopova4, Mélanie Chesneau65, Alain Le Moine66, Pierrick Guérif65, Jean-Paul Soulillou67, Marc Abramowicz68, Magali Giral67, Judith Racapé69, Umberto Maggiore18, Sophie Brouard67, Daniel Abramowicz70. 1. Renal Unit, CUB Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium Medical Genetics Department, ULB, Brussels, Belgium. 2. Joint Research Unit 1064, French Institute of Health and Medical Research, Nantes, France. 3. Nephrology, Hospital del Mar, Barcelona, Spain. 4. Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 5. Nephrology, Charité Campus Mitte, Berlin, Germany. 6. University Department of Nephrology, Skopje, Macedonia. 7. Nephrology and Transplantation Medicine, Wrocław, Poland. 8. Internal Medicine, Nephrology, Istanbul School of Medicine, Istanbul, Turkey. 9. Nephrology P, Rigshospitalet, Copenhagen, Denmark. 10. Nephrology and Transplantation, Geneva University Hospitals, Geneva, Switzerland. 11. Department of Medicine III-Nephrology, Hypertension and Renal Transplantation, Krankenhaus Elisabethinen Linz, Linz, Austria. 12. Richard Bright Renal Centre, Southmead Hospital, North Bristol NHS Trust, Bristol, UK. 13. Department of Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands. 14. Department of Transplantation, Rabin Medical Center, Tel Aviv University Sackler School of Medicine, Tel Aviv, Israël. 15. Nephrology Department, CHU Lille, Lille, France. 16. Section of Transplantation Immunology, Department of Surgery, Medical University of Vienna, Vienna, Austria. 17. Department of Immunology, Genetics and Pathology, Section of Clinical Immunology, Uppsala University, Sweden. 18. UOS Trapianti Rene Pancreas, Centro Trapianti di Parma, Az. Ospedaliero-Universitaria di Parma, Parma, Italy. 19. Department of Nephrology, University Hospital Aachen, Aachen, Germany. 20. Wake Forest School of Medicine, Department of Surgery, Section of Transplantation, Winston-Salem, NC, USA. 21. U.O.C. Trapianti D'Organo, L'Aquila, Italy. 22. Department of Nephrology, Renal Transplantation Centre Ljubljana, University Medical Centre Ljubljana, Ljubljana, Slovenia. 23. Kidney Diseases, Radboudumc Nijmegen, Nijmegen, The Netherlands. 24. Renal Transplant Unit, Department of Nephrology, Academic Medical Center, Amsterdam, The Netherlands. 25. Service de Néphrologie, Unité de Transplantation Rénale et Pancréatique, CHU Sud, Amiens, France. 26. Department of Translational Medicine, Amedeo Avogadro University, AOU Maggiore della Carità di Novara, Novara, Italy. 27. Service de Néphrologie-Dialyse-Transplantation, CHU Angers, Angers, France. 28. Hôpital de jour de Néphrologie, service de Néphrologie et Transplantation Rénale, Nouvel hôpital Civil, CHU de Strasbourg, Strasbourg, France. 29. Nephrology, Hospital Universitari Val d'Hebron, Barcelona, Spain. 30. Nephrology, Tepecik Training and Research Hospital, Izmir, Turkey. 31. Regional Nephrology Unit, Belfast City Hospital, Belfast, UK. 32. Nefrologia, Dialisi e Trapianto di rene, AO Torrette Umberto I, Ancona, Italy. 33. Nephrology/Transplantation, Royal Liverpool University Hospital, Liverpool, UK. 34. Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium. 35. Nephrology Ward, Department of Internal Medicine, University Hospital Pilsen, Pilsen, Czech Republic. 36. Nephrology, Istanbul University, Cerrahpasa Medical Faculty, Istanbul, Turkey. 37. General Surgery, Tepecik Training and Research Hospital, Yenisehir, Izmir, Turkey. 38. Servicio de Nefrología, Hospital Universitario, A Coruña, Spain. 39. Transplant Centre, University Hospital Louis Pasteur Kosice, Kosice, Slovakia. 40. Department of Medical Sciences, University of Turin, Turin, Italy. 41. 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. 42. Nephrology, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain. 43. Service Néphrologie, Hôpital Victor Provo, Roubaix, France. 44. Nierziekten, LUMC, Leiden, The Netherlands. 45. Néphrologie - Médecine Interne - Hypertension Pédiatrique, Hôpital des Enfants, Toulouse, France. 46. Service Néphrologie - Immunoclinique, CHRU, Hôpital Bretonneau, Tours, France. 47. Unidad de Gestión Clínica de Urología y Nefrología, Hospital Universitario Virgen del Rocío, Sevilla, Spain. 48. Nephrology Department, University Hospital of Lille, Lille, France. 49. Department of Nephrology and Rheumatology, University Medicine Göttingen, Göttingen, Germany. 50. Service de Néphrologie, CHRU Avenue Georges Clémenceau, Caen, France. 51. Division of Nephrology, Hypertension and Clinical Pharmacology, Inselspital, University Hospital Bern, Bern, Switzerland. 52. Transplantation rénale, CHU Grenoble, Grenoble, France. 53. Servicio de Nefrología, Hospital General Universitario de Alicante, Alicante, Spain. 54. Internal Medicine 1, Nephrology, University Hospital Ulm, Ulm, Germany. 55. Nephrology, Hospital Germans Trias i Pujol, Badalona (Barcelona), Spain. 56. University Hospital Hamburg Eppendorf (UKE), Hamburg, Germany. 57. Université Paris Descartes et Hôpital Necker, Paris, France. 58. Service d'hémodialyse et de Néphrologie, Hôpital Robert Boulin, Libourne, France. 59. Service de Néphrologie, CHRU de Brest, Brest, France. 60. Nephrology Unit, Hôpital Saint Louis, Paris, France. 61. Kidney Diseases, Kidney Transplant Az. Osp. G. Brotzu, Cagliari, Italy. 62. Servicio de Nefrología, Hospital Universitario Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain. 63. Department of Nephrology, University Hospital Krakow, Krakow, Poland. 64. Nephrology, Marmara School of Medicine Hastanesi, Istanbul, Turkey. 65. Institute of Transplantation Urology and Nephrology, Nantes University Hospital, Nantes, France. 66. Renal Unit, CUB Hôpital Erasme, Université Libre de Bruxelles (ULB), Brussels, Belgium. 67. 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. 68. Medical Genetics Department and IRIBHM (Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire), ULB, Brussels, Belgium. 69. Research Center of Epidemiology, Biostatistics and Clinical Research, School of Public Health, ULB, Brussels, Belgium. 70. Nephrology-Renal Transplantation Department, Universitair Ziekenhuis Antwerp, Antwerp, Belgium Université Libre de Bruxelles (ULB), Brussels, Belgium.
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.
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.
Authors: Estefania Nova-Lamperti; Marco Romano; Sofia Christakoudi; Manohursingh Runglall; Reuben McGregor; Paula Mobillo; Yogesh Kamra; Tjir-Li Tsui; Sonia Norris; Susan John; Dominic A Boardman; Robert I Lechler; Giovanna Lombardi; Maria P Hernandez-Fuentes Journal: Transplantation Date: 2018-01 Impact factor: 4.939