RENAL PAPILLARY CYTOPLASMIC GRANULARITY AND POTASSIUM-DEPLETION INDUCED BY CARBONIC-ANHYDRASE INHIBITORS IN RATS

Renal papillary cytoplasmic granularity (RPCG) induced by carbonic anh ydrase inhibitors (CAIs) in rats is characterized by the accumulation of dense secondary lysosomes in epithelial, endothelial, and interstit ial cells and may be related to drug-induced potassium depletion. Fema le Sprague-Dawley rats were given the CAI, acetazolamide, by gavage. H alf were supplemented with 1% potassium chloride in the drinking water . Two treated groups were allowed to recover for 1 or 2 mo. Potassium supplementation inhibited RPCG by 80% but produced little amelioration of the mild 13% decrease in serum potassium induced by 200 mg/kg/day acetazolamide for 28 days. Acetazolamide-induced RPCG is reversible be cause 1- and 2-mo recovery periods decreased the incidence by 75% and 80%, respectively. The results support the hypothesis that RPCG is rel ated to potassium depletion secondary to carbonic anhydrase inhibition . Because supplementation of potassium chloride had little effect on s erum potassium, these data suggest that depletion of renal medullary p otassium content is important in the pathogenesis of RPCG as previousl y suggested by others. Other types of diuretics that produce hypokalem ia as a side effect may not deplete medullary potassium since RPCG has not been reported in humans or animals given these drugs.