Effect of gentamicin on renal function in the rat

The functional correlates of gentamicin nephrotoxicity were studied in rats injected with gentamicin, 100 mg/kg b.wt. per day, for 1 to 6 days. After 4 days of injections, a significant decrease in urine osmolality was detected in association with a rise in blood urea nitrogen and serum creatinine. These changes became more pronounced after 5 days of injections. Injecting gentamicin for 3 to 5 days had no discernible effect on the capacity of the distal nephron to reabsorb solute free water during a saline load compared to the control group. Tubular secretion of para-aminohippurate (PAH) was significantly greater in rats injected with gentamicin for 4 to 5 days than in the control group. Increased uptake of PAH by renal cortical slices was detected after 1 day of gentamicin treatment and reached a peak effect after 5 days of injections. Probenecid completely inhibited the augmented PAH uptake. No stimulation of the organic base transport system was observed. Three days of gentamicin treatment did not alter intracellular water or electrolyte content of kidney cortical slices. The data suggest that gentamicin specifically stimulates the organic acid transport system and that this effect may represent an early functional correlate of gentamicin nephrotoxicity.