Relationship between allograft cyclosporin concentrations and P‐glycoprotein expression in the first month following renal transplantation

Abstract

The immunosuppressant cyclosporin is a P‐glycoprotein substrate whose impaired function has been associated with an increased risk of cyclosporin‐induced nephrotoxicity following renal transplantation. This study investigated the relationship between blood and allograft cyclosporin concentration, and the effect of P‐glycoprotein expression. Fifty biopsy samples were obtained from 39 renal transplant recipients who received cyclosporine as part of maintenance immunosuppression. Blood cyclosporin concentrations (2 hours post‐dose) were obtained from clinical records, matching allograft cyclosporin concentrations were measured in frozen biopsy tissue by LC‐MS/MS, and allograft P‐glycoprotein expression was assessed by immunohistochemistry. Blood and allograft cyclosporin concentrations in the first month post‐transplantation ranged from 505‐2005 μg/L and 0.01‐16.7 ng/mg tissue, respectively. Dose was the only significant predictor of allograft cyclosporin concentrations (adjusted R² = 0.24, F‐statistic = 11.52, p = 0.0019), with no effect of P‐glycoprotein expression or blood cyclosporin concentrations. P‐glycoprotein expression is not the major determinant of allograft cyclosporin concentrations.

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