Cisplatin nephrotoxicity.
Cisplatin is used widely in the treatment of a large number of carcinomas. The clinical use of cisplatin, however, can be complicated by myelotoxicity, ototoxicity and intestinal toxicity; we review briefly cisplatin nephrotoxicity. The principal route of its excretion is via the kidney, and accumulation of cisplatin in the renal cortex has been demonstrated. Three to five days following administration of cisplatin to rats, degenerative changes appear in the proximal tubule, including cytoplasmic vacuolization, tubular dilatation and pyknotic and hydropic degeneration. A decrease in renal plasma flow was observed very early on in patients receiving cisplatin at a dose of 20 mg/m2 over a period of 4 h, and an increase in urinary enzymes occurred rapidly. Hypomagnesaemia, hypocalcaemia and hypokalaemia were frequent. The mechanism of cisplatin nephrotoxicity remain unclear. Biotransformation of cisplatin could play an important role; a decrease in sulphydryl groups in the kidney may be a primary event, and reactive metabolites may be formed. The incidence of cisplatin nephrotoxicity has been observed to decrease when patients are prehydrated, and it was proposed recently that administration of a calcium blocker might reduce the nephrotoxic effects of cisplatin. The clinical recommendations are to avoid rapid cisplatin infusion rates (over 1 mg/kg per hour) and to induce hydration at least during and after cisplatin administration. New compounds with the same or better antitumour activity and less toxicity should be prepared. At present, carboplatin appears to be preferable to cisplatin because of the reduced incidence of untoward effects.
Fillastre
J P
JP
U 295, Institut National de la Santé et de la Recherche Médicale, Faculté de Médecine-Pharmacie de Rouen, Saint-Etienne-du-Rouvray, France.
Raguenez-Viotte
G
G
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D002945:Cisplatin / Q000009:adverse effects / Q000633:toxicity*; D004285:Dogs; D006801:Humans; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D051379:Mice; D051381:Rats
D002945:Cisplatin