Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure.
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.
Michael J
MJ
Casey
Xuerong
X
Wen
Liise K
LK
Kayler
Ravi
R
Aiyer
Juan C
JC
Scornik
Herwig-Ulf
HU
Meier-Kriesche
D000328:Adult; D000368:Aged; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016559:Tacrolimus / Q000097:blood; D013997:Time Factors
D006680:HLA Antigens; D007518:Isoantibodies; D016559:Tacrolimus