Survival Benefit with Kidney Transplants from HLA-Incompatible Live Donors

Abstract

BACKGROUND A report from a high-volume single center indicated a survival benefit of receiving a kidney transplant from an HLA-incompatible live donor as compared with remaining on the waiting list, whether or not a kidney from a deceased donor was received. The generalizability of that finding is unclear. METHODS In a 22-center study, we estimated the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting-list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group). We analyzed the data with and without patients from the highest-volume center in the study. RESULTS Recipients of kidney transplants from incompatible live donors had a higher survival rate than either control group at 1 year (95.0%, vs. 94.0% for the waiting-list-or-transplant control group and 89.6% for the waiting-list-only control group), 3 years (91.7% vs. 83.6% and 72.7%, respectively), 5 years (86.0% vs. 74.4% and 59.2%), and 8 years (76.5% vs. 62.9% and 43.9%) (P<0.001 for all comparisons with the two control groups). The survival benefit was significant at 8 years across all levels of donor-specific antibody: 89.2% for recipients of kidney transplants from incompatible live donors who had a positive Luminex assay for anti-HLA antibody but a negative flow-cytometric cross-match versus 65.0% for the waiting-list-or-transplant control group and 47.1% for the waiting-list-only control group; 76.3% for recipients with a positive flow-cytometric cross-match but a negative cytotoxic cross-match versus 63.3% and 43.0% in the two control groups, respectively; and 71.0% for recipients with a positive cytotoxic cross-match versus 61.5% and 43.7%, respectively. The findings did not change when patients from the highest-volume center were excluded. CONCLUSIONS This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.)

The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology

“…As noted by Orandi et al, “Increasing numbers of transplant physicians are encountering this problem, which may become more common given new therapeutic agents and new organ allocation policies” 10.…”

“…A growing number of centers perform high‐risk renal transplants, thereby intensifying the need for improved assessment of subclinical ABMR 11 and the clinical implications of its kinetics and response to therapy 10. Advances in antibody testing by multiplex bead array assays have greatly enhanced the sensitivity and precision of detection of circulating DSAs 12.…”

Safety, immunogenicity, pharmacokinetics, and efficacy of degradation of anti-HLA antibodies by IdeS (imlifidase) in chronic kidney disease patients

“…These strategies use preconditioning with cycles of high‐dose intravenous Ig (IVIg), or plasmapheresis combined with low‐dose IVIg,5 but can include other agents such as rituximab 6, 7. Desensitization has increased transplant rates, reduced waiting times, and provided a significant survival benefit for patients with DSA compared with waiting for an HLA‐compatible transplant 8. Transplant of an HLA‐incompatible kidney after desensitization is, however, associated with an increased risk of ABMR, in both the short and longer term 4, 9…”

Pilot Experience with ABO-Incompatible Kidney Transplantation as a Second Transplant

“…In highly sensitized patients, the immunologic barrier is associated with an increased risk of antibody-mediated rejection and poor graft survival. Recently, living donor kidney transplantation after desensitization has been reported to provide a significant survival benefit for patients with HLA sensitization, as compared with waiting for a compatible organ [18,19] . The regimen for ABOincompatible kidney transplantation including plasmapheresis for removal of anti-A/B antibodies and administration of RIT for inhibition of antibody production may be useful for desensitization in second transplantation, which may have a higher risk related to increased levels of preformed HLA antibodies or non-HLA antibodies that might cause damages of the graft.…”