Studies on the pathogenesis of cisplatin-induced hypomagnesemia in rats

After three weekly intraperitoneal injections of cisplatin (2.5 mg/kg body wt), male Wistar rats developed chronic hypomagnesemia, which was evident from the second week and persisted throughout the 8-week experiments. Plasma magnesium concentration was 0.69 +/- 0.01 mM in cisplatin-treated rats compared to 0.80 +/- 0.02 mM in pair-fed control rats (P less than 0.01) in the eighth week of experimentation. Despite a similar dietary magnesium intake, urinary excretion of magnesium in cisplatin-treated rats was inappropriately high, relative to the lower plasma magnesium concentration, indicating the presence of renal magnesium wasting induced by cisplatin. During the 3 weeks of cisplatin injections, metabolic balance studies indicated abnormal renal excretion and a reduction in the fractional intestinal absorption of magnesium. A compensatory period of significantly greater retention of magnesium then occurred in cisplatin-treated rats beginning in the fourth week. Clearance and recollection micropuncture studies in a separate group of rats revealed normal magnesium and calcium transport in the superficial proximal and distal nephron. Following acute MgCl2 infusion, the urinary excretion of magnesium and calcium were significantly higher in cisplatin-treated rats than in control rats; however, micropuncture studies of superficial nephrons failed to demonstrate abnormal transport of these divalent cations. It is possible, therefore, that 7 weeks of cisplatin treatment led to tubular adaptation that might have obscured the defect in magnesium reabsorption. Morphological examination indicated that pathological changes were confined to the S3 segment of proximal corticomedullary nephrons.(ABSTRACT TRUNCATED AT 250 WORDS)