Can a pharmacokinetic approach to immunosuppression eliminate ethnic disparities in renal allograft outcome?

Abstract

Although renal allograft outcome correlates more closely with area under the concentration time curve (AUC) for cyclosporin (CsA) compared with the 12-h trough level (C0), few studies have prospectively evaluated pharmacokinetic monitoring in kidney transplantation. This paper describes a study designed to evaluate the impact of a novel approach to CsA-based immunosuppression on ethnic differences in renal allograft outcome. Sixty (32 African Americans and 28 Caucasians) renal transplant recipients were treated with cyclosporin-based triple therapy. Morning and evening doses were independently adjusted to reach an AUC0-12 of 6600-7200 ng h/mL and a C0 of 250-325 ng/mL, respectively. AUCs were measured within 48 h of starting CsA, and as often as necessary to maintain target levels. Only two patients experienced significant adverse events related to immunosuppression. One (Caucasian) developed haemolytic uremic syndrome and was converted to tacrolimus, while another (African American) developed acute vascular rejection. One graft was lost (Caucasian) due to death with a functioning graft. An average of 8 AUCs (range 5-13) were measured in the first 3 months. AUCs were significantly higher in African Americans compared with Caucasians only in the first and second month. C0 values were similar in both groups throughout the study period. A pharmacokinetic approach to immunosuppression allows individualization of CsA exposure, and appears to reduce ethnic disparities in renal allograft outcome.