Rethinking the advantage of zero-HLA mismatches in unrelated living donor kidney transplantation: implications on kidney paired donation.

The OPTN/UNOS Kidney Paired Donation (KPD) Pilot Program allocates priority to zero-HLA mismatches. However, in unrelated living donor kidney transplants (LDKT)-the same donor source in KPD-no study has shown whether zero-HLA mismatches provide any advantage over >0 HLA mismatches. We hypothesize that zero-HLA mismatches among unrelated LDKT do not benefit graft survival. This retrospective SRTR database study analyzed LDKT recipients from 1987 to 2012. Among unrelated LDKT, subjects with zero-HLA mismatches were compared to a 1:1-5 matched (by donor age ±1 year and year of transplantation) control cohort with >0 HLA mismatches. The primary endpoint was death-censored graft survival. Among 32,654 unrelated LDKT recipients, 83 had zero-HLA mismatches and were matched to 407 controls with >0 HLA mismatches. Kaplan-Meier analyses for death-censored graft and patient survival showed no difference between study and control cohorts. In multivariate marginal Cox models, zero-HLA mismatches saw no benefit with death-censored graft survival (HR = 1.46, 95% CI 0.78-2.73) or patient survival (HR = 1.43, 95% CI 0.68-3.01). Our data suggest that in unrelated LDKT, zero-HLA mismatches may not offer any survival advantage. Therefore, particular study of zero-HLA mismatching is needed to validate its place in the OPTN/UNOS KPD Pilot Program allocation algorithm.

Calcineurin inhibitors in kidney transplantation: friend or foe?

PURPOSE OF REVIEW: The utilization of calcineurin inhibitors (CNI) in kidney transplantation has dramatically improved short-term outcomes but significant gains in long-term outcomes have proved elusive. Nephrotoxicity is the major problem associated with CNIs and is responsible for the disappointing progress seen in long-term graft survival. In this review, we assess CNI efficacy as well as the latest strategies employed to limit long-term CNI nephrotoxicity. RECENT FINDINGS: Three CNI sparing strategies - CNI withdrawal, CNI avoidance, and CNI minimization - are evaluated with discussion of key studies such as the Efficacy Limiting Toxicity Elimination-Symphony and Spare-the-Nephron studies. Recent breakthroughs in transplant immunosuppression are discussed such as the BENEFIT and BENEFIT-EXT studies, which have led to the recent US Food and Drug Administratrion approval of belatacept, a novel T-cell costimulation blocker. SUMMARY: For now, CNIs remain the proven standard of care in modern immunosuppression. However, some novel agents may challenge the role CNIs play in kidney transplantation in the very near future.