Marina Noris1, Giuseppe Remuzzi. 1. aIRCCS - Istituto di Ricerche Farmacologiche 'Mario Negri', Clinical Research Center for Rare Diseases 'Aldo e Cele Daccò', Ranica, and 'Centro Anna Maria Astori' Science and Technology Park Kilometro Rosso bUnit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
Abstract
PURPOSE OF REVIEW: Several genetic and acquired abnormalities leading to abnormal activation of the alternative pathway of complement have been identified in patients with atypical hemolytic uremic syndrome (aHUS). The purpose of this review is to shed light on how advances in the understanding of aHUS pathogenesis have impacted on prevention and cure of aHUS recurrence after kidney transplantation. RECENT FINDINGS: Studies over the past decade have shown that the risk of posttransplant recurrence of aHUS depends on the underlying genetic abnormality. The risk is high in patients with mutations in genes encoding circulating complement proteins and regulators, whereas patients with mutations in membrane cofactor protein generally show good transplant outcome. Given the poor outcome associated with recurrence, isolated renal transplantation had been contraindicated in aHUS patients. Combined kidney-liver transplantation and prophylactic plasma exchange have been used to prevent posttransplant recurrences. More recent data have provided evidence about the efficacy of the anti-C5 monoclonal antibody eculizumab in the prevention and treatment of posttransplant aHUS recurrences. SUMMARY: This review summarizes recent advances on preventing and managing aHUS recurrence after kidney transplantation and discusses the issues that still need clarification.
PURPOSE OF REVIEW: Several genetic and acquired abnormalities leading to abnormal activation of the alternative pathway of complement have been identified in patients with atypical hemolytic uremic syndrome (aHUS). The purpose of this review is to shed light on how advances in the understanding of aHUS pathogenesis have impacted on prevention and cure of aHUS recurrence after kidney transplantation. RECENT FINDINGS: Studies over the past decade have shown that the risk of posttransplant recurrence of aHUS depends on the underlying genetic abnormality. The risk is high in patients with mutations in genes encoding circulating complement proteins and regulators, whereas patients with mutations in membrane cofactor protein generally show good transplant outcome. Given the poor outcome associated with recurrence, isolated renal transplantation had been contraindicated in aHUS patients. Combined kidney-liver transplantation and prophylactic plasma exchange have been used to prevent posttransplant recurrences. More recent data have provided evidence about the efficacy of the anti-C5 monoclonal antibody eculizumab in the prevention and treatment of posttransplant aHUS recurrences. SUMMARY: This review summarizes recent advances on preventing and managing aHUS recurrence after kidney transplantation and discusses the issues that still need clarification.
Authors: Donal J Sexton; Scott Reule; Craig A Solid; Shu-Cheng Chen; Allan J Collins; Robert N Foley Journal: Hemodial Int Date: 2015-02-17 Impact factor: 1.812
Authors: Karolis Azukaitis; Eva Simkova; Mohammad Abdul Majid; Matthias Galiano; Kerstin Benz; Kerstin Amann; Clemens Bockmeyer; Radha Gajjar; Kevin E Meyers; Hae Il Cheong; Bärbel Lange-Sperandio; Therese Jungraithmayr; Véronique Frémeaux-Bacchi; Carsten Bergmann; Csaba Bereczki; Monika Miklaszewska; Dorottya Csuka; Zoltán Prohászka; Paul Killen; Patrick Gipson; Matthew G Sampson; Mathieu Lemaire; Franz Schaefer Journal: J Am Soc Nephrol Date: 2017-05-19 Impact factor: 14.978