EFFECT OF CHRONIC CISPLATIN ADMINISTRATION ON PHOSPHATE AND GLUCOSE-TRANSPORT BY THE RENAL BRUSH-BORDER MEMBRANE

Cisplatin (CIS-diamine dichloroplatinum) is a highly nephrotoxic antineoplastic agent which may cause acute renal failure and renal tubular dysfunction. In the present study we have examined the effect of chronic cisplatin administration on sodium-dependent P-32-phosphate and H-3 glucose transport by the renal brush border membrane vesicles (BBMV). Our results indicate that both transport mechanisms were significantly reduced at the BBMV following cisplatin therapy due to an increased K(m) (0.13+/-0.09 vs. 0.34+/-0.09 mM; p = < 0.01) without significant change in Vmax (56+/-18 vs. 44+/-17 pM/mg/s). The results of these studies indicate that cisplatin causes a diffuse renal injury in the proximal segment of the nephron altering both transport mechanisms. Possible mechanisms of cisplatin nephrotoxicity are discussed.