Gordon J A, Dillingham M A, Guggenheim S J, Grossfeld P D, Anderson R J
J Lab Clin Med. 1983 Jun;101(6):903-10.
The present studies were carried out to delineate the mechanism of the polyuric state and renal concentration defect seen after gentamicin. Gentamicin was given at a dosage of 100 mg/kg/day subcutaneously for either 4 or 5 days to Sprague-Dawley rats and resulted in a reversible, polyuric form of acute renal failure. This nonoliguric acute renal failure was accompanied by significant polydipsia and a renal concentrating defect 11 days after gentamicin. To assess the role of polydipsia in the polyuria and renal concentrating abnormality, water intake was restricted in gentamicin-treated animals to match intake of control animals. Elimination of the polydipsia failed to eliminate the polyuria and to improve the renal concentrating abnormality. Postdehydration plasma vasopressin levels were higher in gentamicin-treated than control animals, suggesting that the renal concentrating defect was nephrogenic in origin. Daily urinary prostaglandin E2 excretion was comparable in gentamicin-treated and control animals. However, indomethacin failed to improve urinary concentrating ability, suggesting that the renal concentrating defect was prostaglandin E2 independent. Finally, depressed postdehydration inner medullary tonicity was found in gentamicin-treated animals In summary, gentamicin administration in the rat was associated with a reversible polyuric form of acute renal failure and a renal concentrating defect. This concentration defect was nephrogenic in origin, independent of polydipsia and prostaglandin E2, and was associated with a decrease in inner medullary tonicity.
本研究旨在阐明庆大霉素治疗后出现的多尿状态及肾浓缩功能障碍的机制。将100mg/kg/天的庆大霉素皮下注射给Sprague-Dawley大鼠，持续4天或5天，可导致可逆性的多尿型急性肾衰竭。这种非少尿型急性肾衰竭伴有显著的烦渴，且在给予庆大霉素11天后出现肾浓缩功能障碍。为评估烦渴在多尿及肾浓缩异常中的作用，对接受庆大霉素治疗的动物限制水摄入，使其与对照动物的摄入量相匹配。消除烦渴未能消除多尿，也未能改善肾浓缩异常。庆大霉素治疗组动物脱水后血浆血管加压素水平高于对照组动物，提示肾浓缩功能障碍源于肾性因素。庆大霉素治疗组和对照组动物每日尿前列腺素E2排泄量相当。然而，吲哚美辛未能改善尿浓缩能力，提示肾浓缩功能障碍与前列腺素E2无关。最后，发现庆大霉素治疗组动物脱水后髓质内层张力降低。总之，给大鼠使用庆大霉素会导致可逆性的多尿型急性肾衰竭及肾浓缩功能障碍。这种浓缩功能障碍源于肾性因素，与烦渴和前列腺素E2无关，且与髓质内层张力降低有关。
