Peri-transplant eculizumab for preventing antibody-mediated rejection in kidney transplant recipients at high immunologic risk: a systematic review with design-stratified evidence synthesis

Abstract

Highly sensitized candidates, preformed donor-specific antibodies, and ABO incompatibility restrict access to kidney transplantation and increase antibody-mediated rejection (AMR) risk. We systematically evaluated peri-transplant eculizumab-containing prophylaxis in high-immunologic-risk kidney transplantation. We searched PubMed, Europe PMC, Ovid Embase, Web of Science Core Collection, Ovid CENTRAL, ClinicalTrials.gov, WHO ICTRP, and supplementary sources; database searches ended 10 June 2026, and registry searches ended 20 August 2026. A total of 31 reports were included; 30 were linked to 14 studies or registry projects, and one pathology report was retained qualitatively. In the only randomized trial, centrally confirmed AMR occurred in 5/51 recipients in both the eculizumab and standard-desensitization groups [risk ratio (RR) 1.00, 95% confidence interval (CI) 0.31–3.25]. A historical comparison reported AMR in 2/26 versus 21/51 recipients (RR 0.19, 95% CI 0.05–0.74), but treatment era, post-transplant plasma exchange, and clinical management changed concurrently. An 80-recipient single-arm study reported three AMR events by week 9. Long-term follow-up showed no consistent graft-survival or kidney-function advantage, while persistent donor-specific antibodies and chronic microvascular injury remained evident. Eculizumab can provide terminal complement blockade within selected combination prophylaxis, but randomized evidence does not establish an incremental reduction in AMR. Definitive trials require standardized background therapy, rescue criteria, long-term graft outcomes, and infection surveillance. This systematic review was registered in PROSPERO (CRD420261484542). https://www.crd.york.ac.uk/PROSPERO/ , identifier CRD420261484542.