INCREASED NEPHROTOXICITY OF GENTAMICIN IN PYELONEPHRITIC RATS

Multiple factors may increase the nephrotoxic potential of aminoglycosides. We studied gentamicin susceptibility of kidneys infected with Escherichia coli. Several parameters of renal function, histological changes on light and electron microscopy and drug levels in renal parenchyma were compared in pyelonephritic and normal rats treated with low doses (10 mg/kg/Q8 hr for 3 days), or high doses (60 mg/kg/day for 14 days), of gentamicin. A significant increase (P < 0.01) in .beta.-galactosidase and protein excreted in urea over a period of 17 days associated with severe changes in diuresis and osmolality was noted in the infected treated rats (low doses) compared with normal, treated, infected or control animals. Histological modifications compatible with gentamicin nephrotoxicity were more persistent in the infected treated animals. A significant decrease in 14C inulin (P < 0.01) and 3H-PAH clearance and secretion (P < .02) was observed in the infected treated rats receiving high doses of antibiotics. Celllular necrosis and tubular desquamation also were more severe in this group. Gentamicin levels in the cortex and medulla of infected animals were significantly higher than in the normals (P < 0.01) and might have been responsible for the increased toxicity noted in the pyrelonephritic animals. Infected kidneys appeared to be more susceptible to the nephrototoxic potential of gentamicin.