AHUS is a thrombotic microangiopathy (TMA) triggered by alternate complement pathway (AP) dysregulation. In 60% of patients, a pathogenic variant can be identified in one of several genes critical for AP regulation. Another 10% have a factor H antibody. Prior to the use of eculizumab, a terminal complement blocker, ESRD occurred in 70% of native disease and 90% of transplant kidneys despite plasma therapy. Eculizumab, a monoclonal anti-C5 antibody has improved the survival of patients with aHUS; however guidance on the optimal use post-transplant setting is absent.

We report the clinical course of 9 patients (8 female) with aHUS who underwent kidney transplantation with prophylactic eculizumab. All patients were on eculizumab preoperatively and have remained on treatment. 8 of the 9 patients were female and the age at transplant ranged from 6 to 40 yr. Pathogenic variants were identified in CFH (5 patients) and FI (3 patients). 1 patient with FI mutation also had a heterozygous CFHR1-CFHR3 deletion and low titer CFH autoantibodies while one patient had no acquired or genetic complement abnormality. 7 patients received living unrelated and 2 received deceased donor transplants. The effectiveness of complement blockade was monitored by a functional C5 assay. 4 patients were induced with basiliximab and 3 with thymoglobulin and initial maintenance was with tacrolimus, mycophenolate and prednisone. Mean follow up was 2.6 yr (range 2 mo to 5 yr). Mycophenolate was withdrawn in 2 patients due to infections (Parvo B19 in 1 and CMV viremia and adenoviral hemorrhagic cystitis in 1). There was one rejection episode (Banff 1B). Low Mg was seen in 5 and was managed by replacement +/- amiloride. All patients have excellent allograft function with a mean creatinine of 1.05 mg/dl (range 0.27 -1.7). Although 2 patients had donor specific antibodies pre transplant, no patient has had AMR or recurrence of hemolysis or TMA.

This aHUS case series, the largest report of a single center post-transplant cohort, emphasizes the safety and apparent efficacy of prophylactic eculizumab to prevent recurrence of aHUS in the post-transplant setting. Eculizumab may also protect against the consequences of anti-HLA Ab binding within the allograft. Further study is required to determine whether eculizumab can be withdrawn after a period of quiescence post-transplant.

CITATION INFORMATION: Kumar A, Stewart Z, Reed A, Orozco D, Smith R, Nester C, Thomas C. Successful Prophylactic Use of Eculizumab in aHUS Kidney Transplant Patients: A Report of 9 Cases. Am J Transplant. 2016;16 (suppl 3).

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