Effect of human leukocyte antigen mismatching on the outcomes of pediatric kidney transplantation: a systematic review and meta-analysis.

BACKGROUND: Kidney transplantation is regarded as the optimal treatment for pediatric patients with end-stage renal disease. Here, we address a controversial topic in pediatric kidney transplantation by performing a quantitative evaluation of the effect of human leukocyte antigen (HLA) mismatching on the outcomes of pediatric kidney transplantation.

METHODS: We systematically searched PubMed, EMBASE and the Cochrane Library from their inception to 31 December 2016 for cohort studies assessing the risk ratio (RR) of HLA mismatching on pediatric kidney transplantation. Outcome measures included graft failure, rejection and all-cause mortality. RRs and 95% confidence intervals (CIs) were used as estimates of effect size in random-effect models.

RESULTS: Eighteen studies comprising a total of 26 018 pediatric recipients were included in the evaluation. Compared with 0-1 HLA-DR mismatch, 2 mismatches significantly increased the risk of graft failure at 1 year (RR: 1.41, 95% CI: 1.11-1.80), 3 years (RR: 1.28, 95% CI: 1.08-1.52), 5 years (RR: 1.21, 95% CI: 1.04-1.41) and 10 years (RR: 1.30, 95% CI: 1.02-1.67). For HLA-A + B, the 5-year graft failure risk was higher for 2-4 mismatches compared with 0-1 mismatch (RR: 3.17, 95% CI: 1.20-8.36), but not for 3-4 compared with 0-2 mismatches (RR: 1.49, 95% CI: 0.79-2.80).

CONCLUSIONS: Based on pooled analysis, HLA-DR and HLA-A + B are important factors affecting post-transplant outcomes, especially graft failure, in pediatric recipients. Additional randomized controlled trials with higher quality evidence are needed for further investigation.