Cyclosporine pharmacokinetics and risk of recurrent rejection in recipients of simultaneous pancreas/kidney transplants

Recipients of a simultaneous pancreas/kidney transplant (SPK) appear to have a greater incidence of acute rejection than do recipients of a kidney- alone transplant. These patients are also susceptible to multiple rejection episodes. Because of this, optimal immunosuppression is imperative in these patients. Cyclosporine A (CsA) based immunosuppression remains the mainstay of therapy, anti therefore, optimization of this often unpredictable drug is necessary. We looked at 14 consecutive SPK recipients and assessed the utility of a single 1-month pharmacokinetic study in predicting the risk of acute rejection. Each pharmacokinetic study was analyzed by both monoclonal fluorescence polarization immunoassay (TDX) and high performance liquid chromatography (HPLC). Due to the small sample size and the high rate of primary rejection (12/14 patients), we chose a novel endpoint, that of recurrent rejection. Seven of the 14 patients studied developed recurrent rejection. The patients without recurrent rejection had significantly higher areas under the concentration curve (AUCs) than did patients with recurrent rejection: 4,663 ± 1,460 vs. 2,454 ± 1,717 ng-h/ml (p < 0.05) by HPLC and 6.669 ± 2.556 vs. 3,661 ± 1,956 ng-h/ml (p < 0.05) by TDX. We propose that a single 1-month AUC has potential utility in identifying a subset of SPK patients with poor CsA absorption at risk for recurrent rejection.