Effect of immunosuppression for first kidney or kidney/pancreas transplant on sensitization at the time of second transplant

Background: Previously transplanted patients are more likely to be sensitized, leading to prolonged waitlist times and decreased graft survival. This analysis of the United Network for Organ Sharing kidney/pancreas transplant database investigates factors at the time of first transplant associated with increased sensitization in patients undergoing second transplantation. METHODS.: Records of nonsensitized patients (panel reactive antibodies [PRA] <20%) receiving a primary transplant in 1999 or later were analyzed to determine whether immunosuppressive agents at the time of first transplant were associated with a change in PRA from first to second transplant. Variables included gender, race, human leukocyte antigen (HLA) mismatch, rabbit antithymocyte globulin (RATG), interleukin-2 receptor antagonists, tacrolimus (FK), cyclosporine A (CSA), and mycophenolate mofetil/sodium (MMF). Results: For the primary endpoint of increase in PRA greater than or equal to 20%, African Americans (AA) versus non-AA (OR 2.63, P<0.0001) and HLA nonzero mismatch versus zero mismatch (OR 2.90, P<0.0001) were associated with increased sensitization. The effect of immunosuppressive regimen depended on race and HLA status. In non-AAs/HLA mismatch (1-6), interleukin-2 receptor antagonists versus RATG (OR 1.40, P=0.001), CSA versus FK (OR 1.69, P<0.001) and no MMF versus MMF (OR 1.39, P<0.001) were also associated with increased sensitization. In AAs/HLA mismatch (1-6), no induction versus RATG (OR 1.59, P=0.031) and CSA versus FK (OR 1.68, P=0.006) were associated with increased sensitization. Conclusions: These data suggest a reduced risk of sensitization at the time of second transplant when using more potent immunosuppression with RATG, FK, and MMF for nonsensitized primary kidney or kidney/pancreas transplant patients. These effects seem to be related to race and HLA mismatch.