Julien Zuber1,2, Marie Frimat2,3, Sophie Caillard2,4, Nassim Kamar2,5, Philippe Gatault2,6, Florent Petitprez7, Lionel Couzi2,8, Noemie Jourde-Chiche2,9, Valérie Chatelet2,10, Raphael Gaisne11, Dominique Bertrand2,12, Jamal Bamoulid2,13, Magali Louis2,14, Rebecca Sberro Soussan15,2, David Navarro15,16, Pierre-Francois Westeel2,17, Luc Frimat2,18, Charlotte Colosio2,19, Antoine Thierry2,20, Joseph Rivalan2,21, Laetitia Albano2,22, Nadia Arzouk2,23, Emilie Cornec-Le Gall2,24, Guillaume Claisse2,25, Michelle Elias2,26, Khalil El Karoui2,27, Sophie Chauvet2,28, Jean-Philippe Coindre2,29, Jean-Philippe Rerolle2,30, Leila Tricot2,31, Johnny Sayegh2,32, Cyril Garrouste2,33, Christophe Charasse2,34, Yahsou Delmas2,8, Ziad Massy2,35, Maryvonne Hourmant2,11, Aude Servais15,2, Chantal Loirat2,36, Fadi Fakhouri2,11, Claire Pouteil-Noble2,37, Marie-Noelle Peraldi2,38, Christophe Legendre15,2, Eric Rondeau2,39, Moglie Le Quintrec2,40, Véronique Frémeaux-Bacchi2,7. 1. Department of Nephrology and Kidney Transplantation, University Hospital Center (CHU) Necker, Paris Descartes University-Sorbonne Paris Cité, Paris, France; julien.zuber@aphp.fr. 2. French Study Group of Atypical Hemolytic Uremic Syndrome, France. 3. Department of Nephrology and Kidney Transplantation, CHU Lille, University of Lille, Lille, France. 4. Department of Nephrology and Kidney Transplantation, The University Hospitals of Strasbourg, Strasbourg, France. 5. Department of Nephrology and Organ Transplantation, CHU Rangueil, INSERM (Institut National de la Santé et de la Recherche Médicale) U1043, IFR-BMT (Institut Fédératif de Recherche Bio-Médicale de Toulouse), University Paul Sabatier, Toulouse, France. 6. Department of Nephrology and Kidney Transplantation, CHU de Tours, Tours, France. 7. Cordelier Research Center, INSERM UMRS 1138, Paris, France. 8. Department of Nephrology and Kidney Transplantation, CHU de Bordeaux, Bordeaux University, CNRS-UMR (Centre National de la Recherche Scientifique-Unité Mixte de Recherche) 5164, Bordeaux, France. 9. Department of Nephrology, C2VN, INSERM, INRA (Institut National de la Recherche Agronomique), CHU de Marseille, Aix-Marseille University, Marseille, France. 10. University Center of Kidney Diseases, CHU de Caen, Caen, France. 11. Department of Nephrology and Kidney Transplantation, CHU de Nantes, Nantes, France. 12. Department of Nephrology and Kidney Transplantation, CHU de Rouen, Rouen, France. 13. Department of Nephrology and Kidney Transplantation, CHRU de Besançon, Besançon, France. 14. Department of Nephrology and Kidney Transplantation, CHU de Dijon, Dijon, France. 15. Department of Nephrology and Kidney Transplantation, University Hospital Center (CHU) Necker, Paris Descartes University-Sorbonne Paris Cité, Paris, France. 16. Department of Nephrology and Kidney Transplantation, Curry Cabral Hospital, Central Lisbon University Hospital Centre, Lisbon, Portugal. 17. Department of Nephrology and Kidney Transplantation, CHU d'Amiens, Amiens, France. 18. Department of Nephrology and Kidney Transplantation, CHU de Nancy, Nancy, France. 19. Department of Nephrology and Kidney Transplantation, CHU de Reims, Reims, France. 20. Department of Nephrology and Kidney Transplantation, CHU de Poitiers, Poitiers, France. 21. Department of Nephrology and Kidney Transplantation, CHU de Rennes, Rennes, France. 22. Department of Nephrology and Kidney Transplantation, CHU de Nice, Nice, France. 23. Department of Nephrology and Kidney Transplantation, CHU Pitié-Salpétrière, Paris, France. 24. Department of Nephrology and Kidney Transplantation, CHU de Brest, Brest, France. 25. Department of Nephrology and Kidney Transplantation, CHU de Saint Etienne, St-Etienne, France. 26. Department of Nephrology and Kidney Transplantation, Kremlin-Bicêtre Hospital, Paris, France. 27. Department of Nephrology and Kidney Transplantation, Henri-Mondor Hospital, Créteil, France. 28. Department of Nephrology, Georges Pompidou European Hospital, Paris, France. 29. Department of Nephrology, Hospital Center du Mans, Le Mans, France. 30. Department of Nephrology and Kidney Transplantation, CHU de Limoges, Limoges, France. 31. Department of Nephrology and Kidney Transplantation, CH de Foch, Suresnes, France. 32. Department of Nephrology and Kidney Transplantation, CHU de Angers, Angers, France. 33. Department of Nephrology and Kidney Transplantation, CHU de Clermont Ferrand, Clermont Ferrand, France. 34. Department of Nephrology, CH du St Brieuc, St Brieuc, France. 35. Department of Nephrology, CHU Ambroise-Paré, Boulogne-Billancourt, France. 36. Department of Nephrology, University Hospital Robert Debré, Paris, France. 37. Department of Nephrology and Kidney Transplantation, CHU de Lyon, Lyon, France. 38. Department of Nephrology and Kidney Transplantation, CHU St Louis, Paris, France. 39. Department of Nephrology and Kidney Transplantation, CHU Tenon, Paris, France; and. 40. Department of Nephrology and Kidney Transplantation, CHU de Montpellier, Montpellier, France.
Abstract
BACKGROUND: Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country. METHODS: To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016. RESULTS: The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients. CONCLUSIONS: Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.
BACKGROUND:Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country. METHODS: To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016. RESULTS: The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients. CONCLUSIONS: Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.
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Authors: Larry A Greenbaum; Christoph Licht; Vasileios Nikolaou; Imad Al-Dakkak; Janet Green; Christian Stefan Haas; Elena Román-Ortiz; Hae Il Cheong; Lisa Sartz; Rita Swinford; Ioannis Tomazos; Benjamin Miller; Spero Cataland Journal: Kidney Int Rep Date: 2020-05-19