The Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys... Show moreThe Eurotransplant Senior Program (ESP) has expedited the chance for elderly patients with kidney failure to receive a timely transplant. This current study evaluated survival parameters of kidneys donated after brain death with or without matching for HLA-DR antigens. This cohort study evaluated the period within ESP with paired allocation of 675 kidneys from donors 65 years and older to transplant candidates 65 years and older, the first kidney to 341 patients within the Eurotransplant Senior DR-compatible Program and 334 contralateral kidneys without (ESP) HLADR antigen matching. We used Kaplan-Meier estimates and competing risk analysis to assess all cause mortality and kidney graft failure, respectively. The log-rank test and Cox proportional hazards regression were used for comparisons. Within ESP, matching for HLA-DR antigens was associated with a significantly lower five-year risk of mortality (hazard ratio 0.71; 95% confidence interval 0.530.95) and significantly lower cause-specific hazards for kidney graft failure and return to dialysis at one year (0.55; 0.35-0.87) and five years (0.73; 0.53-0.99) post-transplant. Allocation based on HLA-DR matching resulted in longer cold ischemia (mean difference 1.00 hours; 95% confidence interval: 0.32-1.68) and kidney offers with a significantly shorter median dialysis vintage of 2.4 versus 4.1 yrs. in ESP without matching. Thus, our allocation based on HLA-DR matching improved five-year patient and kidney allograft survival. Hence, our paired allocation study suggests a superior outcome of HLA-DR matching in the context of old-for-old kidney transplantation. Show less
Significance Statement This randomized trial demonstrates the safety and efficacy of conversion from calcineurin inhibitor (CNI)? to belatacept-based maintenance immunosuppression in renal... Show moreSignificance Statement This randomized trial demonstrates the safety and efficacy of conversion from calcineurin inhibitor (CNI)? to belatacept-based maintenance immunosuppression in renal transplant recipients 6?60 months post-transplant. Patients converted to belatacept showed sustained improvement in renal function associated with an acceptable safety profile consistent with prior experience and a smaller treatment difference in acute rejection postconversion compared with that observed in earlier studies in de novo renal allograft recipients. These results favor the use of belatacept as an alternative to continued long-term CNI-based maintenance immunosuppression, which is particularly relevant for CNI-intolerant patients, including those who experience nephrotoxicity. These data help inform clinical practice guidelines regarding the conversion of such patients to an alternative immunosuppressive drug regimen.Background Calcineurin inhibitors (CNIs) are standard of care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial evaluated the efficacy and safety of conversion from CNI-based to belatacept-based maintenance immunosuppression in kidney transplant recipients.Methods Stable adult kidney transplant recipients 6?60 months post-transplantation under CNI-based immunosuppression were randomized (1:1) to switch to belatacept or continue treatment with their established CNI. The primary end point was the percentage of patients surviving with a functioning graft at 24 months.Results Overall, 446 renal transplant recipients were randomized to belatacept conversion (n=223) or CNI continuation (n=223). The 24-month rates of survival with graft function were 98% and 97% in the belatacept and CNI groups, respectively (adjusted difference, 0.8; 95.1% CI, ?2.1 to 3.7). In the belatacept conversion versus CNI continuation groups, 8% versus 4% of patients experienced biopsy-proven acute rejection (BPAR), respectively, and 1% versus 7% developed de novo donor-specific antibodies (dnDSAs), respectively. The 24-month eGFR was higher with belatacept (55.5 versus 48.5 ml/min per 1.73 m(2) with CNI). Both groups had similar rates of serious adverse events, infections, and discontinuations, with no unexpected adverse events. One patient in the belatacept group had post-transplant lymphoproliferative disorder.Conclusions Switching stable renal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a similar rate of death or graft loss, improved renal function, and a numerically higher BPAR rate but a lower incidence of dnDSA. Clinical Trial registry name and registration number: A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix? (Belatacept)-Based, NCT01820572 Show less
