Cisplatin nephrotocity: Role of filtration and tubular transport of cisplatin in isolated perfused kidneys

Abstract Isolated perfused rat kidneys were used to determined the contribution of filtration and tubular transport of cisplatin to its nephrotoxicity. Perfusion of kidney with 0.5 mM cisplatin concomitantly reduced tubular reabsorption of electrolytes and glomerular filtration rate in a time-dependent manner. These renal functional changes were similar to those obtained following in vivo cisplantin treatment ( mg/kg). In vitro exposure to cisplantin reduced the renal clearance of organic ions without reducing renal perfused flow, suggesting that renal hemodynamic changes do not mediate cisplatini-induced proximal tubular dysfunction. Inhibition of organic ion transport also was observed in non-filtering perfused kidneys treated with 0.5 mM cisplatin, implying that filtration of cisplatin is not a prerequisite for induction of toxicity. These data also suggest that cisplatin transport from a basolateral site may be important in the development of acute nephrotoxicity