The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors

Abstract

Background: Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor.

Methods: Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival.

Results: Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus.

Conclusions: A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.

Figure 1

Cox multivariate regressions were performed with the survival time of kidney allografts from deceased donors as the dependent variable and HLA mismatch as the primary explanatory variable with 0-mismatch as the reference. Blue diamonds represent the observed HRs for HLA mismatch for a reduced model with age, sex, and transplant era as covariates, while the red squares represent the observed HR values for the full model as presented in Table 2. The solid blue line is the fitted line for the reduced model with an intercept of 1.02 (0.98, 1.07), p < 0.0001, and a slope of 0.16 (0.15, 0.17), p < 0.0001, while the red line is fitted to the full model observed values with intercept 1.04 (0.98, 1.10), p < 0.0001, and slope of 0.11 (0.09, 0.12), p < 0.0001. Error bars are the 95% confidence intervals for the respective points on the fitted lines.

Figure 2

A Cox multivariate regression was performed with the survival time of kidney allografts from deceased donors as the dependent variable and an HLA mismatch categorical variable with 27 ordered triples as the primary explanatory variable with [0,0,0] triple as the reference. HR values for the full model are presented in Table 3. The red line is fitted to the full model observed values with intercept 1.04 (1.0, 1.09), p < 0.0001, and slope of 0.11 (0.09, 0.12), p < 0.0001. This is the same line that results from fitting a line to the collapsed HLA mismatch categories 0–6 in Figure 1. See Supplementary Figure 4 for fitted line and weighted confidence limits.