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Abstract: SA-PO871

Obinutuzumab Induction in a Kidney Transplant Recipient With Atypical Hemolytic Uremic Syndrome due to CFHR1/CFHR3 Gene Mutation and Anti-Complement Factor H Antibody

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Favi, Evaldo, Universita degli Studi di Milano, Milano, Lombardia, Italy
  • Molinari, Paolo, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy
  • Iesari, Samuele, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy
  • Alfieri, Carlo, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy
  • Castellano, Giuseppe, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy
  • Ferraresso, Mariano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy
  • Cresseri, Donata Carmela, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Lombardia, Italy
Introduction

For many years, atypical hemolytic uremic syndrome (aHUS) has represented a relative contraindication to kidney transplantation (KT). The wide spread use of the anti-complement component 5 monoclonal antibody eculizumab has reduced post-transplant aHUS relapse and allograft loss rates. However, the optimal management of patients with DEficiency of CFHR plasma proteins and Autoantibody Positive form of Hemolytic Uremic Syndrome (DEAP-HUS) remains debated. In this particular subset of recipients, the benefits of repeated apheresis and/or chronic eculizumab administration should be weighed against the risk of fatal infections, severe adverse events, and exorbitant costs.

Case Description

We report the case of a 45-year-old woman with end-stage renal disease due to CFHR1/CFHR3 gene homozygous deletion-associated aHUS who underwent deceased-donor KT despite persistently elevated anti-CFH antibody titers. While on the transplant waiting list, she was not given any aHUS-targeted therapy. At transplant, she received an induction scheme including eculizumab (900 mg before surgery), basiliximab (20 mg on day 0 and day 4), methylprednisolone, and obinutuzumab (1000 mg on day 6). As a maintenance, we used LCP-tacrolimus, mycophenolate mofetil, and prednisone. The post-operative course was uneventful. After 1-year follow-up, she is doing well with excellent allograft function, undetectable anti-CFH antibody, full CD19+ cells depletion, and no signs of aHUS activity. Remarkably, no obinutuzumab infusion-related adverse reactions, severe infectious complications, or hematologic disorders were recorded.

Discussion

Although anecdotal, our experience suggests that peri-transplant administration of eculizumab and obinutuzumab safely and effectively inhibits complement activation and block anti-CFH antibody production, thus ensuring long-lasting protection from DEAP-HUS relapse, at a reasonable cost. For the first time, we have also provided evidence in vivo that obinutuzumab-induced B-cell depletion does not necessarily require complement activation. Such preliminary finding could provide the rationale for further studies investigating combined eculizumab and obinutuzumab use for antibody-mediated rejection prophylaxis or treatment.