Background: When kidney transplants fail, transplant medications are discontinued to reduce immunosuppression-related risks. However, retransplant candidates are at risk for allosensitization which prolonging immunosuppression may minimize. We hypothesized that for these patients, a prolonged immunosuppression withdrawal after graft failure preserves nonsensitization status (PRA 0%) better than early immunosuppression withdrawal.
Methods: We retrospectively examined subjects transplanted at a single center between July 1, 1999 and December 1, 2009 with a non–death-related graft loss. Subjects were stratified by timing of immunosuppression withdrawal after graft loss: early (≤3 months) or prolonged (>3 months). Retransplant candidates were eligible for the main study where the primary outcome was nonsensitization at retransplant evaluation. Non-retransplant candidates were included in the safety analysis only.
Results: We found 102 subjects with non–death-related graft loss of which 49 were eligible for the main study. Nonsensitization rates at retransplant evaluation were 30% and 66% for the early and prolonged immunosuppression withdrawal groups, respectively (P=0.01). After adjusting for cofactors such as blood transfusion and allograft nephrectomy, prolonged immunosuppression withdrawal remained significantly associated with nonsensitization (adjusted odds ratio=5.78, 95% CI [1.37–24.44]). No adverse safety signals were seen in the prolonged immunosuppression withdrawal group compared to the early immunosuppression withdrawal group.
Conclusions: These results suggest that prolonged immunosuppression may be a safe strategy to minimize sensitization in retransplant candidates and provide the basis for larger or prospective studies for further verification.
1 Department of Medicine, University of Florida, Gainesville, FL.
2 Department of Surgery, Montefiore Medical Center, Bronx, NY.
3 Department of Medicine, University of Washington Medical Center, Seattle, WA.
4 Department of Pathology, University of Florida, Gainesville, FL.
5 Bristol-Meyers Squibb, Princeton, NJ.
6 Address correspondence to: Michael J. Casey, M.D., Division of Nephrology, Hypertension, and Renal Transplantation, P.O. Box 100224, Gainesville, FL 32610-0224.
This work is supported in part by the NIH/NCATS Clinical and Translational Science Award to the University of Florida UL1 TR000064.
The authors declare no conflicts of interest.
M.J.C. is the corresponding author and participated in designing the research, gathering and analyzing the data, and writing the article. He received support from the NIH/NCATS Clinical and Translational Science Award to the University of Florida UL1 TR000064. X.W. participated in designing the research, and gathering and analyzing the data. L.K.K. participated in writing the article. R.A. participated in gathering the data and writing the article. J.C.S. participated in designing the research and writing the article. H.-U.M.-K. participated in designing the research and writing the article. H.-U.M.-K. is an Adjunct Professor of Medicine at the University of Florida and received no support for this study, but he was previously employed by Astellas Pharma and is presently employed by Bristol-Myers Squibb.
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Received 30 April 2013. Revision requested 16 May 2013.
Accepted 7 January 2014.