[Experimental study of drug-induced acute renal failure. Recovery after renal impairment caused by the administration of low molecular weight dextran and kanamycin in water-deprived rats].

Various risk factors for the development of acute renal failure (ARF) have been pointed out clinically. Hypotension, excessive aminoglycoside exposure, and dehydration were identified as highly significant acute insults. Adenine nucleotide level in the renal tissue and morphological changes were investigated to clarify the recovery of renal tissue after gradual impairment caused by the administration of low molecular weight dextran (LMWD) and Kanamycin (KM) in water-deprived rats. Male SD rats, deprived of water for 2 days, received various dosages of LMWD (10, 15, 20, 30 ml/kg, i.p.) and KM (300 mg/kg, s.c.) concomitantly. The rats were killed on the 5th day and the level of adenine nucleotide in the renal tissue was determined by high pressure liquid chromatography (HPLC). The kidney was examined by electron microscopy. For comparison, LMWD and KM were administered to a second group of rats in tap water ad libitum, using the same dosages. The group dehydrated rats was more liable to have ARF. Electron microscopy disclosed changes in the kidney, indicating a disorder of the lysosome of the epithelial cells, not the mitochondria, of the proximal tubules. In this group, a decrease in Energy Charge value (EC = (ATP + 1/2ADP)/(ATP + ADP + AMP)) occurred later than both functional and morphological impairments. Both the EC values and the microscopic examination of the rats with the LMWD.KM-induced ARF showed that water deprivation greatly increased the potential for ARF. The degree of renal impairment depended on the dosage of LMWD. Both excessive aminoglycoside exposure and water deprivation were significant risk factors.