薬物起因性急性腎不全発症に関する実験的研究水欠乏性脱水時の低分子デキストランおよびKallamycin併用による腎障害とその回復力

Abstract

SD系雄性ラットを用い水欠乏性脱水に低分子デキストランとKMを投与し, 組織的および腎組織のadenine nucleotideを検討した.1)脱水群は自由飲水群に比べて腎障害を来し易かった.2)脱水群の腎機能および組織学的変化はLMWD (Low molecular weight dextran)の増量に並行して増悪した.3)脱水群の腎組織のATP値は腎機能低下に先んじて徐々に低下したが, EC(=ηATP+1/2 ADPΛ/ηATP+ADP+AMPΛ)値は腎機能障害に遅れて変動した.腎障害を起こすLMWDの少ない投与領域での腎組織のEG値は可逆性変化の範囲で腎組織の回復能は認められるが, LMWDの増量により腎障害は不可逆性変化を来すものと考えられた.4) LMWD, KM, 脱水条件の3因子が重なると不可逆性のARF (Acute renal failure)になり易かった

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.