Individualization of Immunosuppressive therapy: I. Sirolimus Improves Outcomes in African-American Renal Transplant Recipients

Abstract

Introduction African-American renal transplant recipients are prone to acute rejection episodes and graft loss owing to genetic, pharmacokinetic, cultural, and socioeconomic factors. While more intense exposures to antirejection agents can mitigate this propensity, heightened immunosuppressive regimens are accompanied by an array of toxicities. Our study sought to examine the impact of a combination of sirolimus (SRL) and cyclosporine (CsA) on the outcomes of African-Americans vs Caucasians. Materials and Methods The outcomes of African-Americans treated with either CsA-prednisone (Pred, n = 90) or SRL-CsA-Pred (n = 86) were compared with 148 SRL-CsA-Pred-treated Caucasians. Results The addition of SRL to a CsA-Pred regimen reduced the rate of acute rejection episodes within 2 years in African-Americans from 43.3% to 17% ( P = .004), a value similar to that observed in Caucasian patients (18%). At 2 years, the graft survival rate of 79% among African-American patients treated with SRL-CsA-Pred was similar to that in the Caucasian cohort (80%). The respective patient survival rates also were similar: 93% and 90%, respectively. Multivariate analysis of 5-year outcomes among patients treated with SRL-CsA-Pred revealed the hazard ratios of African-Americans vs Caucasians to actually be reduced for acute rejection (.22; P = .01) and for death (.15; P = .01), but similar for chronic rejection (.77; P = NS) and graft loss (1.03; P = NS). Conclusion The use of SRL-based regimens mitigated the otherwise enhanced risk for acute rejection episodes or graft loss otherwise experienced by CsA-treated African-American renal transplant recipients.