African American (AA) Renal Transplant Recipients (RTR) Require Higher Tacrolimus Doses to Achieve Target Levels Compared to White RTR: Does Clotrimazole (CTZ) Help?

Abstract

The number of African Americans on the kidney waiting list is increasing in the USA. Several studies showed that AAs are at higher risk for rejection and graft loss. Due to genetic polymorphisms, AA may metabolize CNI faster than White individuals. The goal of this study is to evaluate the tacrolimus dose required to reach therapeutic levels and to assess the impact of CTZ on tacrolimus metabolism in AA compared to White patients. One hundred forty-two AA renal transplant recipients (RTR) were compared to 312 White RTR. Demographics were similar in both groups (Table 1). Induction therapy and maintenance immunosuppression were similar in both groups and included tacrolimus, mycophenolate acid (MPA) and steroids. The goal in all RTR was to maintain a 12 hour trough level of 10-15 ng/ml in the first 3 months, 8-10 ng/ml for the first year and 5-8 ng/ml thereafter. To achieve these levels, AA require a significantly higher dosage of tacrolimus compared to Whites (5.9±2.9 vs. 3.6±2 mg/d respectively, p< 0.0001). By multivariate analysis, tacrolimus dose requirements were not affected by age, gender, MPA or prednisone dose, diabetes and renal function. Both male and female AA required a higher dose of tacrolimus compared to White male and female respectively. Adding CTZ to the RTR regimen significantly reduced the tacrolimus dose requirements in all RTR. When CTZ was used, the tacrolimus dose requirement was not statistically significant between AA and Whites (2.6±1.2 mg/d vs. 1.8±1.5 mg/d, p=0.07).Table: [*=p<0.05]We conclude that AA required a higher tacrolimus dose to reach the desired trough level in RTR compared to White RTR. The use of CTZ significantly reduces the tacrolimus dose and eliminates the need for higher doses of tacrolimus in AA RTR. Thus, for AA who would require a high dose of tacrolimus, use of CTZ may benefit these RTR in order to avoid both the higher dose and cost of tacrolimus.