Dieperink H, Leyssac P P, Starklint H, Kemp E
Eur J Clin Invest. 1986 Feb;16(1):69-77. doi: 10.1111/j.1365-2362.1986.tb01310.x.
Renal function was studied in rats treated with cyclosporin A (CyA). Peroral CyA 25 mg kg-1 day-1 depressed glomerular filtration rate (GFR) from 1284 +/- 429 to 500 +/- 228 microliters min-1 g-1 kidney weight (KW) (P less than 0.01). Absolute rate of proximal tubular reabsorption (APR) decreased from 1075 +/- 437 to 468 +/- 203 microliters min g KW-1 (P less than 0.01). Proximal tubular fractional reabsorption (PFR) was 67.7 and 68.5% measured with the TT/OT and fractional lithium-clearance methods, respectively. Amiloride had no effect on lithium-clearance in CyA treated rats. Acute isotonic volume expansion increased GFR and APR towards normal, while PFR remained increased. Increased sodium clearance did not normalize renal function. CyA intravenously (12.5 mg kg-1) depressed GFR and APR acutely, while PFR increased. Proximal intratubular pressures were low normal (mean 11.6 mmHg). Proximal transit times were prolonged (mean 25.2 s, P less than 0.01). Renal morphology was normal. The data are evidence against a primary tubular damage of CyA, and makes it less likely that the major lesion is located to the glomerular membrane. The results suggest that CyA nephrotoxicity mainly is due to a haemodynamic effect.
研究了用环孢素A（CyA）治疗的大鼠的肾功能。口服CyA 25mg/kg/天可使肾小球滤过率（GFR）从1284±429微升/分钟/克肾重（KW）降至500±228微升/分钟/克KW（P<0.01）。近端肾小管重吸收率（APR）绝对值从1075±437降至468±203微升/分钟/克KW-1（P<0.01）。分别用TT/OT法和锂清除率分数法测得近端肾小管分数重吸收率（PFR）为67.7%和68.5%。氨氯地平对CyA治疗的大鼠的锂清除率无影响。急性等渗容量扩张使GFR和APR恢复正常，而PFR仍升高。钠清除率增加并未使肾功能恢复正常。静脉注射CyA（12.5mg/kg）可急性降低GFR和APR，而PFR升高。近端肾小管内压力处于正常低水平（平均11.6mmHg）。近端转运时间延长（平均25.2秒，P<0.01）。肾脏形态正常。这些数据证明CyA不存在原发性肾小管损伤，且主要病变位于肾小球膜的可能性较小。结果表明，CyA肾毒性主要是由于血流动力学效应。
