Effective immunosuppressive management with belatacept and eculizumab in post-transplant aHUS due to a homozygous deletion of CFHR1/ CFHR3 and the presence of CFH antibodies

Clin Kidney J. 2017 Dec;10(6):742-746. doi: 10.1093/ckj/sfx053. Epub 2017 Jul 10.

Abstract

Atypical haemolytic uraemic syndrome (aHUS) may clinically present as acute renal graft failure resulting from excessive activation of the complement cascade. While mutations of complement-encoding genes predispose for aHUS, it is generally thought to require an additional insult (e.g. drugs) to trigger and manifest the full-blown clinical syndrome. Calcineurin inhibitors (CNIs) used for immunosuppression act as potential triggers, especially in the post-transplantation setting. Therefore, CNI-free immunosuppressive regimens may be beneficial. We report on a 58-year-old woman who developed aHUS with acute graft failure within 20 days after renal transplantation. Genetic investigation revealed a homozygous deletion of the CFH-related 1 (CFHR1) and CFHR3 genes in addition to the presence of autoantibodies against complement factor H (CFH). The patient was treated with plasmapheresis and administration of the complement component 5 (C5) antibody eculizumab, and her immunosuppressive regimen was switched from CNI (tacrolimus) to the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor belatacept. Renal graft function recovered and stabilized over an 18-month follow-up period. We describe the successful management of post-transplant aHUS using a CNI-free immunosuppressive regimen based on eculizumab and belatacept. Ideally, adequate molecular diagnostics, performed prior to transplantation, can identify relevant genetic risk factors for graft failure and help to select patients for individualized immunosuppressive regimens.

Keywords: atypical haemolytic uraemic syndrome; recurrence; renal transplantation.

Publication types

  • Case Reports