Precision Desensitization In The Imlifidase Era: A Systematic Review of Biomarkers, Risk Stratification Models, and Personalized Treatment Algorithms For Hla-Incompatible Kidney Transplantation

Abstract

Highly human leukocyte antigen (HLA)-sensitized kidney transplant candidates with positive crossmatch have limited access to transplantation, prolonged exposure to dialysis, and increased mortality. Imlifidase, an IgG‑cleaving enzyme, can rapidly convert positive crossmatch to a negative crossmatch; however the roles of immunological biomarkers, risk stratification, and personalized treatment protocols remain insufficiently defined. The study systematically searched PubMed, Web of Science, and the Cochrane Library for clinical studies involving adult HLA‑incompatible kidney transplant candidates or recipients treated with imlifidase. Studies reporting donor‑specific antibodies (DSA) or calculated panel reactive antibody (cPRA) together with crossmatch conversion, antibody‑mediated rejection (AMR), patient and graft survival, and safety outcomes were included. Results were synthesized descriptively because of substantial clinical and methodological heterogeneity. Four clinical studies of imlifidase‑treated HLA‑incompatible kidney transplant recipients and one narrative review on biomarker‑based risk models and personalized algorithms met the eligibility criteria, although the narrative review was used solely to provide  conceptual context . Across the clinical cohorts, sample sizes ranged from 19 to 41 recipients, all of whom were highly sensitized, with median or mean cPRA values ranging from 90–100%. Imlifidase converted a positive crossmatch to a negative crossmatch in 89.5–100% of recipients within 24 hours, with short‑ to mid‑term patient survival rates of 87.5–100% and graft survival rates of 84–100%. Early AMR occurred in 22–39% of recipients and was consistently associated with DSA rebound emerging within 3–15 days after imlifidase administration. Current evidence indicates that imlifidase  provides a viable desensitization strategy for highly sensitized, crossmatch‑positive patients who otherwise have limited transplantation options; however, this benefit is tempered by a substantial burden of early AMR associated with DSA rebound. Reliance on small, nonrandomized cohorts and heterogeneous immunosuppressive and monitoring protocols limits the certainty of the available evidence, underscoring the need for prospective multicentre studies to validate composite biomarker‑based risk models and personalized treatment algorithms in imlifidase‑enabled HLA‑incompatible kidney transplantation.

Keywords: Imlifidase, Kidney Transplantation, HLA-Incompatible, Desensitization, Donor-Specific Antibodies.