Change in Mycophenolate and Tacrolimus Exposure by Transplant Vintage and Race

Although both tacrolimus and mycophenolate have improved outcomes after kidney transplant, studies regarding effects of exposure on outcomes, specifically related to racial disparities, are sparse.

In this 8-year longitudinal cohort study of adult kidney transplant recipients, mycophenolate and tacrolimus levels were compared across transplant vintage stratified by non-African Americans versus African Americans. Data were analyzed with standard univariate tests and multivariable regression models.

Our study included 1217 patients (transplanted from 2005-2013) who had tacrolimus and myco-phenolate exposure data, with follow-up through 2015 (53.7% were African Americans). Mean mycophenolate dose was 1672 ± 463 mg/day during the first 3 years posttransplant. Although transplant vintage did not appreciably impact mycophenolate dosing in non-African Americans (0.7 mg/day/y; P = .903), doses significantly decreased in African Americans across transplant vintage (-20.5 mg/day/y; P < .001). Rate of mycophenolate being held or discontinued based on transplant vintage significantly increased in African Americans but did not change in non-African Americans. At the beginning of the study, mean tacrolimus levels were lower in African Americans; however, levels then slightly decreased in non-African Americans (-0.03 ng/mL/y; P = .279) and slightly increased in African Americans (+0.03 ng/mL/y; P = .247), with similar levels by 2013. Higher tacrolimus levels were protective against rejection in African Americans only but were protective against death-censored graft loss in both race/ethnicity groups. Mycophenolate dosing had no appreciable impact on outcomes in African Americans, but higher mycophenolate dosing was a significant risk factor for death-censored graft loss in non-African Americans.

Tacrolimus and mycophenolate exposure levels have significantly changed over time and differed by race/ethnicity. In non-African Americans, those transplanted more recently tended to have lower tacrolimus but similar mycophenolate exposure. Although mycophenolate exposure in African Americans has recently decreased, tacrolimus has increased. Differences in outcomes likely reflect improved understanding of immunosuppressant tolerability by recipient race/ethnicity.