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

Williams, Robert C. PhD; Opelz, Gerhard MD; McGarvey, Chelsea J. MD; Weil, E. Jennifer MD; Chakkera, Harini A. MD

doi: 10.1097/TP.0000000000001115
Original Clinical Science-General

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.

This largest, most contemporary analysis of HLA shows that HLA mismatching is associated with worse transplant outcomes, ordered by number of mismatches and without an independent effect of any specific locus, such as donor-recipient mismatching.

1 Phoenix Epidemiology and Clinical Research Branch, NIH, NIDDK, Phoenix, AZ.

2 Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.

3 Mayo Clinic Hospital, Mayo Clinic, Phoenix, AZ.

4 Division of Nephrology, Mayo Clinic, Phoenix, AZ.

Received 13 July 2015. Revision received 12 November 2015.

Accepted 21 November 2015.

This work was supported in part by Health Resources and Services Administration contract 234-2005-370011C. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

The authors declare no conflict of interest.

R.C.W. is responsible for the design and performance of the statistical analysis, wrote the first draft, acts as corresponding author, and is responsible for the accuracy and integrity of the work. G.O. participated in the design of the analysis, revises the drafts, has final approval on the submission manuscript, and is responsible for the integrity of the work. C.M.G. participated in the design of the analysis and the creation of new variables and covariates, revises the drafts, has final approval on the submission of the article, and is responsible for the integrity of the work. E.J.W. participated in the design of the analysis, particularly the categories for induction and immunosuppression and covariates, revises the drafts, has final approval on the submission of the manuscript, and is responsible for the integrity of the work. H.C. provided the UNOS STAR files for the work, participated in the design of the analysis, particularly the categories for induction and immunosuppression and covariates, revises the drafts, has final approval on the submission of the article, and is responsible for the integrity of the work.

Correspondence: Robert C. Williams, PhD, NIH, NIDDK, PECRB 1550, East Indian School Road, Phoenix, AZ 85014. (williamsr@mail.nih.gov).

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