Cyclosporine nephrotoxicity: associated allograft dysfunction at low trough concentration

A case report on the nephrotoxic effect of cyclosporine in a 9-year-old boy with a kidney transplant is presented. Nephrotoxicity was present even at low trough cyclosporine concentration. The literature on the range of cyclosporine nephrotoxicity is reviewed. Cyclosporine (CsA), a fungal decapeptide first introduced in 1983, has significantly improved the outcome of renal transplantation, and remains the first line immunosupressant for pediatric recipients. CsA has a narrow therapeutic range because of the fine line between adequate immunosuppression and the risk of drug-induced side effects. Furthermore, considerable inter- and intrapatient variability does exist [Filler et al. 1999]. The pre-dose trough concentration is routinely used for therapeutic drug monitoring [Bunchman et al. 1998]. The most significant side effect is nephrotoxicity, which may present differently at different times after transplantation. Renal vasoconstriction, especially involving the afferent renal arterioles, has been strongly implicated as a primary factor in acute reversible CsA nephrotoxicity. Alpha-adrenergic and calcium channel blockade with either verapamil or nifedipine ameliorates vasospasm and impairment of renal function that accompany CsA toxicity. Because of this vasoconstrictive effect, CsA may increase ischemic graft damage in the early posttransplant period. CsA side effects can be eliminated by reducing the dosage of the drug. We present an unusual case of nephrotoxicity and impaired renal function with a very low CsA blood trough concentration (50 ng/ml) on posttransplant treatment. The side effects subsided only after the discontinuation of CsA.