Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome

Julien Zuber , Marie Frimat , Sophie Caillard , Nassim Kamar , Philippe Gatault , Florent Petitprez , Lionel Couzi , Noemie Jourde-Chiche (1, 2) , Valérie Châtelet , Raphaël Gaisne , Dominique Bertrand , Jamal Bamoulid , Magali Louis , Charlotte Colosio , Antoine Thierry , Joseph Rivalan , Laetitia Albano , Nadia Arzouk , Emilie Cornec-Legall , Guillaume Claisse , Michelle Elias , Khalil El Karoui , Sophie Chauvet , Jean-Philippe Coindre , Jean Philippe Rerolle , Leïla Tricot , Johnny Sayegh , Cyril Garrouste , Christophe Charasse , Yahsou Delmas , Ziad Massy , Maryvonne Hourmant , Aude Servais , Chantal Loirat , Fadi Fakhouri , Claire Pouteil Noble , Marie Noelle Peraldi , Christophe Legendre , Eric Rondeau , Moglie Le Quintrec , Veronique Fremeaux-Bacchi

1 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
2 Centre de néphrologie et transplantation rénale [Hôpital de la Conception - APHM]

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.

Mots clés: complement; hemolytic uremic syndrome; kidney transplantation; INHIBITOR ECULIZUMAB; RECURRENCE; MUTATIONS

Domaines: Sciences du Vivant [q-bio]; Médecine humaine et pathologie; Urologie et Néphrologie

Julien Zuber, Marie Frimat, Sophie Caillard, Nassim Kamar, Philippe Gatault, et al.. Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome. Journal of the American Society of Nephrology, 2019, 30 (12), pp.2449-2463. ⟨10.1681/ASN.2019040331⟩. ⟨hal-02556079⟩