Cortical and papillary absorptive defects in gentamicin nephrotoxicity

Renal function was examined in rats given daily injections of gentamicin (100 to 150 mg/kg) for 10 to 14 days. Whole kidney inulin clearance fell and urine volume increased. Single nephron GFR of surface nephrons varied. Some nephrons had no filtration, some had low rates, and some had high rates. Abnormal renal tubular epithelial inulin permeability was demonstrated by microinjection. Micropuncture of individual nephrons early and later in their course demonstrated reduced fluid reabsorption along the proximal convoluted tubule of superficial nephrons. Rates of fluid delivery to the late proximal and distal tubule were elevated. The rate of fluid reabsorption in the superficial loop of Henle was increased. Maximal urine osmolality and papillary tissue content of urea was reduced. The polyuria, therefore, results from decreased fluid reabsorption by proximal tubules and, probably, by papillary collecting ducts. The decrease in proximal fluid reabsorption is probably secondary to impaired solute reabsorption. A decrease in collecting duct fluid absorption can be attributed to the observed decrease in papillary solute concentration.