Use of human renal proximal tubule cell cultures for studying foscarnet-induced nephrotoxicity in vitro.

Foscarnet is an antiviral agent used for the treatment of cytomegalovirus retinitis and acyclovir-resistant herpes simplex virus infections in AIDS patients. Renal impairment has been reported for many patients treated with foscarnet. We have studied the effects of foscarnet on the viability (estimated by neutral red inclusion) and ultrastructure of cultures of human renal proximal tubule cells (HRPTC) isolated from the kidneys of five cadavers and cultured. The degree of foscarnet-induced toxicity was dose dependent and varied among the HRPTC cultures. The data obtained by using the in vitro system of HRPTC mimic the data of the clinical trials in that there is a dose-dependent individual variation among human cases in response to foscarnet treatment. Thus, these cultures are extremely well-suited to investigations of the mechanism of toxicity at the subcellular level.