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      The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts 2: Living Donors, Summary, Guide

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          Abstract

          Background

          Allografts from living donors survive longer than those from deceased donors but the role of HLA mismatching in living kidney donation is still in question. We examined the effect of HLA compatibility on kidney allograft survival from living donors by studying all first adult kidney transplants performed in the United States over 25 years.

          Methods

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

          Results

          There were 66 596 first adult transplants from living donors with 348 960 years of follow-up. We found a linear relationship between HLA mismatch and allograft survival. In adjusted analyses, among all living donors, 1 mismatch conferred a 44% higher risk, whereas 6 mismatches conferred a twofold higher risk of allograft failure. When using 0-mismatched full siblings as a reference, living-donor kidneys reduce the hazard of failure by approximately 34% when compared with deceased donors. Twenty-five years of transplant experience, stratified by donor source, was summarized and presented as a guide for allocation.

          Conclusions

          These data reinforce the importance of optimizing HLA matching to further improve survival in first adult kidney allografts in the future, especially in living unrelated donations, when possible.

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          Most cited references12

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          Conspectus florae Graecae / auctore E. de Halácsy.

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            Living-donor kidney transplantation: a review of the current practices for the live donor.

            The first successful living-donor kidney transplant was performed 50 yr ago. Since then, in a relatively brief period of medical history, living kidney transplantation has become the preferred treatment for those with ESRD. Organ replacement from either a live or a deceased donor is preferable to dialysis therapy because transplantation provides a better quality of life and improved survival. The advantages of live versus deceased donor transplantation now are readily apparent as it affords earlier transplantation and the best long-term survival. Live kidney donation has also been fostered by the technical advance of laparoscopic nephrectomy and immunologic maneuvers that can overcome biologic obstacles such as HLA disparity and ABO or cross-match incompatibility. Congressional legislation has provided an important model to remove financial disincentives to being a live donor. Federal employees now are afforded paid leave and coverage for travel expenses. Candidates for renal transplantation are aware of these developments, and they have become less hesitant to ask family members, spouses, or friends to become live kidney donors. Living donation as practiced for the past 50 yr has been safe with minimal immediate and long-term risk for the donor. However, the future experience may not be the same as our society is becoming increasingly obese and developing associated health problems. In this environment, predicting medical futures is less precise than in the past. Even so, isolated abnormalities such as obesity and in some instances hypertension are no longer considered absolute contraindications to donation. These and other medical risks bring additional responsibility in such circumstances to track the unknown consequences of a live-donor nephrectomy.
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              Quantifying the risk of incompatible kidney transplantation: a multicenter study.

              Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti-HLA donor-specific antibody (DSA). Program-specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15-2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71-6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28-3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98-7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal-quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19-, 1.33- and 1.73-fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22-, 4.09- and 10.72-fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life-saving treatment in jeopardy of regulatory intervention.
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                Author and article information

                Journal
                Transplant Direct
                Transplant Direct
                TXD
                Transplantation Direct
                Lippincott Williams & Wilkins
                2373-8731
                May 2017
                07 April 2017
                : 3
                : 5
                : e152
                Affiliations
                [1] 1 Phoenix Epidemiology and Clinical Research Branch, NIH, NIDDK, Phoenix, AZ.
                [2] 2 Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany.
                [3] 3 Mayo Clinic Hospital, Mayo Clinic, Phoenix, AZ.
                [4] 4 Division of Nephrology, Mayo Clinic, Phoenix, AZ.
                Author notes
                Correspondence: Robert C. Williams, PhD, NIH/NIDDK, Phoenix Epidemiology and Clinical Research Branch, 445 North 5th Street, Suite 210, Phoenix, AZ 85004. ( williamsr@ 123456mail.nih.gov ).
                Article
                TXD50142 00003
                10.1097/TXD.0000000000000664
                5441983
                28573187
                c6209d7e-a28f-4bae-bb3d-961d9cf36182
                Copyright © 2017 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 22 November 2016
                : 8 February 2017
                : 28 February 2017
                Page count
                Pages: 0
                Categories
                016
                Kidney Transplantation
                Custom metadata
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