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Understanding the relationship between the factors that influence long-term kidney transplant survival in order to appropriately select the optimal initial graft remains a key priority for pediatric nephrologists.Using the ANZDATA database, we conducted a retrospective cohort study of pediatric and adolescent primary kidney transplant recipients to assess the relative impact of donor/recipient age difference and HLA mismatches on long-term graft outcomes. The study population included all kidney transplant recipients less than 20 years of age who received a primary kidney transplant in Australia and New Zealand between January 1, 1990 and December 31, 2015. The primary outcome was graft survival following first kidney transplant analysed according to the Kaplan-Meier method. Secondary outcomes included delayed graft function (requiring dialysis in the first 72 hours post-transplant) and graft function at 12 months, as a surrogate marker of long term graft survival.During this 26-year period, 1134 primary kidney transplants were performed in recipients less than 20 years of age. The median follow-up time after the first graft transplant was 10.2 years (IQR 4.2-16.3 years), with 30 recipients lost to follow up (2.6%). During the study period, 405 patients (35.7%) lost their graft with graft survival of 93.8% (95% CI, 92.4%-95.2%) at 1 year post-transplant, 82.5% (95%CI 80.6%-84.4) at 5-years, 65.8% (95% CI, 62.5-69.1%) at 10 years and 49.9% (95% CI, 46.9-54.1%) at 15 years. There was consistently higher graft loss of deceased donor kidneys as compared to live donor kidneys at each time point. On Cox proportional hazards regression, both increasing donor/recipient age difference (adjusted hazard ratio [aHR] 1.09 per 10 years; 95%CI, 1.01-1.18; p=0.03) and increasing HLA mismatch (aHR 1.19 per mismatch; 95%CI, 1.10-1.30; p<0.001) were associated with decreased graft survival. In addition, graft failure was associated with the following factors: Indigenous/Pacific Islander race (when compared to Caucasian race, p<0.001), glomerulonephritis as a cause of ESKD (when compared to CAKUT; p=0.01), use of T-cell or other induction agents (when compared to basiliximab; p=0.009) and increasing recipient age at kidney transplant (p<0.001), when adjusted for baseline immunosuppression.Both donor/recipient age difference and HLA matching are important factors influencing long-term graft outcomes in pediatric kidney transplantation and HLA mismatch remains a strong predictor of graft loss. For pediatric patients without the option of a live donor, we suggest that along with age of the donor and other markers of kidney quality, the degree of HLA mismatch should not be discounted as part of the decision making process in deceased donor allocation.ANZDATA.