Intermediate-Term Graft Loss After Renal Transplantation is Associated With Both Donor-Specific Antibody and Acute Rejection

DeVos, Jennifer M.1,4; Gaber, Ahmed Osama2; Teeter, Larry D.3; Graviss, Edward A3; Patel, Samir J1; Land, Geoffrey A.3; Moore, Linda W.2; Knight, Richard J.2

Transplantation:
doi: 10.1097/01.TP.0000438196.30790.66
Clinical and Translational Research
Abstract

Background: Renal transplant recipients with de novo DSA (dDSA) experience higher rates of rejection and worse graft survival than dDSA-free recipients. This study presents a single-center review of dDSA monitoring in a large, multi-ethnic cohort of renal transplant recipients.

Methods: The authors performed a nested case-control study of adult kidney and kidney-pancreas recipients from July 2007 through July 2011. Cases were defined as dDSA-positive whereas controls were all DSA-negative transplant recipients. DSA were determined at 1, 3, 6, 9, and 12 months posttransplant, and every 6 months thereafter.

Results: Of 503 recipients in the analysis, 24% developed a dDSA, of whom 73% had dDSA against DQ antigen. Median time to dDSA was 6.1 months (range 0.2–44.6 months). After multivariate analysis, African American race, kidney-pancreas recipient, and increasing numbers of human leukocyte antigen mismatches were independent risk factors for dDSA. Recipients with dDSA were more likely to suffer an acute rejection (AR) (35% vs. 10%, P<0.001), an antibody-mediated AR (16% vs. 0.3%, P<0.001), an AR ascribed to noncompliance (8% vs. 2%, P=0.001), and a recurrent AR (6% vs. 1%, P=0.002) than dDSA-negative recipients. At a median follow-up of 31 months, the death-censored actuarial graft survival of dDSA recipients was worse than the DSA-free cohort (P=0.002). Yet, for AR-free recipients, there was no difference in graft survival between cohorts (P=0.66).

Conclusions: Development of dDSA was associated with an increased incidence of graft loss, yet the detrimental effect of dDSA was limited in the intermediate term to recipients with AR.

Author Information

1 Department of Pharmacy, The Methodist Hospital, Houston, TX.

2 Department of Surgery, The Methodist Hospital, Houston, TX.

3 Department of Pathology and Genomic Medicine, The Methodist Hospital Research Institute, Houston, TX.

4 Address correspondence to: Jennifer M. DeVos, Pharm.D, B.C.P.S., Department of Pharmacy, The Methodist Hospital, 6565 Fannin Street DB1-09, Houston, TX 77030.

The authors declare no funding or conflicts of interest.

E-mail: JMDevos@tmhs.org

J.M.D. participated in designing and performing the research, writing the article, and analyzing the data. A.O.G. participated in designing the research and writing the article. L.D.T. participated in designing the research, writing the article, and analyzing the data. E.A.G. participated in designing the research, writing the article, and analyzing the data. S.J.P. participated in designing and performing the research, and writing the article. G.A.L. participated in designing the research and writing the article. L.W.M. participated in designing the research and writing the article. R.J.K. participated in designing and performing the research, writing the article, and analyzing the data.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (www.transplantjournal.com).

Received 17 April 2013. Revision requested 5 May 2013.

Accepted 25 September 2013.

Accepted December 27, 2013

© 2014 by Lippincott Williams & Wilkins