Kidney Transplantation in Patients With aHUS: A Comparison of Eculizumab Prophylaxis Versus Rescue Therapy.

Background: Guidelines advise eculizumab prophylaxis for most kidney transplant recipients with atypical hemolytic uremic syndrome (aHUS). However, recurrence rates may be overestimated, and starting eculizumab at relapse ("rescue therapy") may prevent graft loss. Randomized controlled trials have not compared the efficacy, safety, and costs of different treatment strategies. We performed a comparative study, including a previously described Dutch cohort treated with rescue therapy and a UK cohort using eculizumab prophylaxis.
Methods: In the Netherlands, we selected all adult patients with aHUS who received a kidney transplant between 2010 and 2021 in the Radboud University Medical Center (n = 30) and enriched this cohort with 8 patients who received rescue therapy in other centers. The UK cohort included all adult patients with aHUS at moderate or high risk of recurrence, transplanted between 2013 and 2017 with prophylactic eculizumab.
Results: We included 38 Dutch patients and 35 UK patients. Characteristics were comparable, although the UK cohort included more patients with a complement factor H SCR20 mutation or hybrid gene (31% versus 5%; P < 0.01), and more Dutch patients received living donor kidneys (66% versus 20%; P < 0.001). Follow-up was comparable (the Dutch patients 70.8 mo, range, 10-134; UK patients 55.4 mo, range, 2-95). Eighteen (47%) Dutch patients received rescue therapy. Death-censored graft survival was not significantly different (the Dutch patients 1 y, 3 y, and 6 y: 97.4%, 91.2%, and 87.1%, respectively; UK patients 1 y, 3 y, and 6 y: 97.1%, 88.2%, and 65.6%, respectively, log-rank P = 0.189).
Conclusions: In a population characterized by low prevalence of "very high risk" genes, who were predominantly transplanted using an endothelial protective regime, death-censored graft survival with eculizumab rescue therapy was not inferior to prophylaxis.
Competing Interests: N.C.A.J.v.d.K. and J.F.M.W. received grant support from the Dutch Board of Health Insurance Companies to conduct the CUREiHUS study. N.C.A.J.v.d.K. received consultancy fees from Roche Pharmaceuticals and Novartis and is a subinvestigator in the APL2-C3G trial, Apellis. J.F.M.W. received consultancy fees from Alexion and Novartis. C.D. is a subinvestigator in the APL2-G3G trial, Apellis. N.S.S. has provided consultancy for Alexion Pharmaceuticals. D.K. has received consultancy income from Gyroscope Therapeutics, Alexion Pharmaceuticals, Novartis, Apellis, and Sarepta. The other authors declare no conflicts of interest.
(Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)