The impact of human leukocyte antigen mismatching on graft survival and mortality in adult renal transplantation

BACKGROUND Human leukocyte antigen (HLA) was important biological barrier to a successful transplantation. Quantitative evaluations of the effect of HLA mismatching on heart, liver, umbilical cord blood, and hematopoietic stem cell transplantation, have previously been reported. In new era of immunosuppression, the reported magnitude effect of HLA mismatching on survival outcomes of kidney transplantation was controversial. In addition, the current kidney allocation guideline recommendations in different countries were inconsistent in term of HLA mismatching. We undertake this study to conduct a systematic review and meta-analysis to assess the magnitude effect of HLA mismatching in adult kidney transplantation, with a particular focus on graft survival and mortality. METHODS The present systematic review and meta-analysis protocol was conducted following the Meta-analysis of Observational Studies in Epidemiology protocol (MOOSE-P) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis protocol (PRISMA-P). PubMed, EMBASE, Cochrane library Database will be searched without language restriction. Studies fulfill the following criteria will be eligible: included study cohorts comprising adult recipients; reported the association between HLA mismatching (per mismatches or HLA-A, -B, -DR mismatches) and posttransplant survival outcomes; provided effect estimates of hazard ratios (HRs) with 95% confidence interval (CIs). The incidence of measured outcomes was defined according to the European Renal Best Practice Transplantation Guidelines and Kidney Disease: Improving Global Outcomes Guidelines. RESULTS This study will quantitatively assess the association of HLA per mismatches, DR-antigen mismatches, A-antigen mismatches, and B-antigen mismatches with survival outcomes of overall graft failure, death-censored graft failure, all-cause mortality, and mortality with a functioning graft. CONCLUSION This study will determine the issues on what extent HLA compatibility influenced recipient and graft survival and which HLA antigen plays a more important role in kidney transplantation. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017071894.