Changes in Renal Brush-Border Sodium-Dependent Transport Systems in Gentamicin-Treated Rats

Changes in Renal Brush-Border Sodium-Dependent Transport Systems in Gentamicin-Treated Rats

<P> To elucidate the mechanism of gentamicin induced renal dysfunction, renal functions and activities of various proximal tubular transport systems were studied in gentamicin-treated rats (Fisher 344). Gentamicin nephrotoxicity was induced by injecting gentamicin sulfate subcutaneously at a dose of 100 mg/kg·day for 7 days. The gentamicin injection resulted in a marked polyuria, hyposthenuria, proteinuria, glycosuria, aminoaciduria, phosphaturia, natriuresis, and kaliuresis, characteristics of aminoglycoside nephropathy. Such renal functional changes occurred in the face of reduced GFR, thus tubular transport functions appeared to be impaired. The polyuria and hyposthenuria were partly associated with a mild osmotic diuresis, but mostly attributed to a reduction in free water reabsorption. In renal cortical brush-border membrane vesicles isolated from gentamicin-treated rats, the Na<SUP>+</SUP> gradient dependent transport of glucose, alanine, phosphate and succinate was significantly attenuated with no changes in Na<SUP>+</SUP>-independent transport and the membrane permeability to Na<SUP>+</SUP>. These results indicate that gentamicin treatment induces a defect in free water reabsorption in the distal nephron and impairs various Na<SUP>+</SUP>-cotransport systems in the proximal tubular brush-border membranes, leading to polyuria, hyposthenuria, and increased urinary excretion of Na<SUP>+</SUP> and other solutes.