Donor-Recipient Non-HLA Variants, Mismatches and Renal Allograft Outcomes: Evolving Paradigms

Despite significant improvement in the rates of acute allograft rejection, proportionate improvements in kidney allograft longevity have not been realized, and are a source of intense research efforts. Emerging translational data and natural history studies suggest a role for anti-donor immune mechanisms in a majority of cases of allograft loss without patient death, even when overt evidence of acute rejection is not identified. At the level of the donor and recipient genome, differences in highly polymorphic HLA genes are routinely evaluated between donor and recipient pairs as part of organ allocation process, and utilized for patient-tailored induction and maintenance immunosuppression. However, a growing body of data have characterized specific variants in donor and recipient genes, outside of HLA loci, that induce phenotypic changes in donor organs or the recipient immune system, impacting transplant outcomes. Newer mechanisms for mismatches in these non-HLA loci have also been proposed during donor-recipient genome interactions with transplantation. Here, we review important recent data evaluating the role of non-HLA genetic loci and genome-wide donor-recipient mismatches in kidney allograft outcomes.

Automated summary

Although there have been significant improvements in the rates of acute allograft rejection, kidney allograft longevity has not seen proportional improvements. Recent research suggests that anti-donor immune mechanisms play a role in cases of allograft loss, even without overt evidence of acute rejection. In addition to evaluating highly polymorphic HLA genes, specific variants in donor and recipient genes outside of the HLA loci have been shown to impact transplant outcomes.