Donor-Specific HLA Antibodies in a Cohort Comparing Everolimus With Cyclosporine After Kidney Transplantation

Abstract

Donor-specific HLA antibodies (DSA) have a negative impact on kidney graft survival. Therefore, we analyzed the occurrence of DSA and antibody-mediated rejection (AMR) in patients from two prospective randomized trials in our center. At 3-4.5 months posttransplant 127 patients were randomized to continue cyclosporine or converted to everolimus therapy. The presence of DSA was prospectively assessed using Luminex assays. AMR was defined according to the Banff 2009 classification. Antibody screening was available in 126 patients with a median follow-up of 1059 days. Seven out of 65 (10.8%) patients on cyclosporine developed DSA after a median of 991 days. In comparison, 14/61 patients (23.0%) randomized to everolimus developed DSA after 551 days (log-rank: p = 0.048). Eight patients on everolimus compared to two patients on cyclosporine developed AMR (log-rank: p = 0.036). Four of 10 patients with AMR-all in the everolimus group-lost their graft. A multivariate regression model revealed everolimus, >3 mismatches and living donor as significant risk factors for DSA. Acute rejection within the first year, >3 mismatches, everolimus and living donor were independent risk factors for AMR. This single center analysis demonstrates for the first time that everolimus-based immunosuppression is associated with an increased risk for the development of DSA and AMR.

Five-Year Outcomes in Kidney Transplant Patients Converted From Cyclosporine to Everolimus: The Randomized ZEUS Study

“…Thus, while the presence of DSA was virtually identical in the two treatment arms, no firm conclusions can be drawn. Previously, Liefeldt et al described an association between everolimus-based immunosuppression and risk of development of DSA and antibody-mediated rejection in a retrospective, single-center study of 126 patients recruited to the ZEUS trial and to another randomized study (40). However, differences in the study populations, statistical methodology and immunosuppressive regimens (notably, steroid withdrawal) (41) mean that results are difficult to interpret.…”

HLA-DR and -DQ Eplet Mismatches and Transplant Glomerulopathy: A Nested Case–Control Study

“…Though the risk for immune-mediated allograft injury may be recognized prior to transplantation in the form of preformed HLA class II DSA (63,70,71) and positive cross-matches (47), anti-class II DSA may also appear posttransplant (72)(73)(74)(75). Knowledge of the eplet load and the immunogenicity of particular eplets, may be used for risk stratification and inform personalized surveillance (DSA monitoring and surveillance biopsies) and therapeutic regimens.…”

Effect of Immunosuppressive Drugs on Humoral Allosensitization after Kidney Transplant

“…In the ZEUS Trial, 74 recipients of kidney transplants on CsA-based immunosuppression were randomized at 4 months post-transplantation to be either maintained on the same regimen or converted to everolimus-based immunosuppression. In a retrospective analysis of a subset of patients, Liefeldt et al 78 reported that 23% of those receiving everolimus had developed dnDSAs compared with only 11% of those who were receiving CsA. This difference was, however, only observed when steroid withdrawal was allowed.…”