Reversibility of Gentamicin Nephrotoxicity in Rats: Recovery during Continuous Drug Administration

The administration of gentamicin, 40 mg/kg per day in two divided doses for 14 days, to male Fischer 344 rats, predictably resulted in acute tubular necrosis and azotemia. Gentamicin administration, in the same dosage, was continued for a total of 42 days because morphologic evidence of regeneration was observed after only 10 days. Despite the continued drug exposure, the blood urea nitrogen and serum creatinine concentrations returned to, and remained in, the normal range by day 21. The ability of the treated rats to produce concentrated urine improved more gradually and was within the normal range by day 34. Renal morphology progressed from acute tubular necrosis on day 10 to near normal morphology on and after day 21. The renal concentration of gentamicin went through two cycles of large increases and decreases. Since the cyclic renal concentration did not correlate with toxicity, we postulated a relationship to the turnover time of injured regenerating rat proximal tubular cells. The mechanism of gentamicin intracellular toxicity remains speculative.