Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome
2019
Zuber, Julien | Frimat, Marie | Caillard, Sophie | Kamar, Nassim | Gatault, Philippe | Petitprez, Florent | Couzi, Lionel | Jourde-Chiche, Noemie | Châtelet, Valérie | Gaisne, Raphaël | Bertrand, Dominique | Bamoulid, Jamal | Louis, Magali | Colosio, Charlotte | Thierry, Antoine | Rivalan, Joseph | Albano, Laetitia | Arzouk, Nadia | Cornec-Legall, Emilie | Claisse, Guillaume | Elias, Michelle | Karoui, Khalil, El | Chauvet, Sophie | Coindre, Jean-Philippe | Rerolle, Jean Philippe | Tricot, Leïla | Sayegh, Johnny | Garrouste, Cyril | Charasse, Christophe | Delmas, Yahsou | Massy, Ziad | Hourmant, Maryvonne | Servais, Aude | Loirat, Chantal | Fakhouri, Fadi | Pouteil Noble, Claire | Peraldi, Marie Noelle | Legendre, Christophe | Rondeau, Eric | Le Quintrec, Moglie | Fremeaux-Bacchi, Veronique | Imagine - Institut des maladies génétiques (IMAGINE - U1163) ; Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM) | Centre de Physiopathologie Toulouse Purpan (CPTP) ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | Département de Néphrologie et Transplantation d'organes [CHU Toulouse] ; Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse] ; Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse) | Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)) ; École Pratique des Hautes Études (EPHE) ; Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU) | Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN) ; Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM] ; Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION) | Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) | Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB) ; Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) | Emmanuel Boussard Foundation Fukuda Foundation for Medical TechnologyKayamori FoundationKayamori Foundation of Informational Science AdvancementSENSHIN Medical Research FoundationSasagawa Scientific Research GrantMukai Science and Technology Foundation
International audience
Mostrar más [+] Menos [-]Inglés. 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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