Heering P, Schadewaldt P, Bach D, Grabensee B
Medizinische Klinik und Poliklinik, Klinik für Nephrologie, Heinrich Heine-Universität Düsseldorf.
Clin Investig. 1993 Dec;71(12):1010-5. doi: 10.1007/BF00180033.
The chronic nephrotoxic effects of cyclosporine (CsA) include proximal tubular atrophy and vacuolization. This study investigated the effect of CsA on renal hemodynamics and segmental electrolyte transport in CsA-treated patients. The clearance of inulin (CIn) and PAH para-amino-hippuric acid (CPAH) was determined; proximal tubular function was studied using a lithium clearance method and calculating tubular phosphate reabsorption per milliliter of glomerular filtrate (TP/CIn). Twenty patients without renal disease were investigated: ten treated with CsA because of nonrenal grafting (group 1) and ten healthy volunteers (group 2). The results obtained were compared with those from 20 renal allograft recipients, of whom ten were treated with CsA and methylprednisolone (group 3) and ten with azathioprine and methylprednisolone (group 4). CIn and CPAH were significantly impaired in patients treated with CsA. No significant impairment of lithium clearance as induced by CsA was observed. The fractional excretion of lithium was slightly increased in patients treated with CsA compared to their respective controls. TP/CIn was lower in graft recipients compared to controls; no impairment of phosphate reabsorption as induced by CsA was found. The fractional tubular excretion of lithium was slightly increased compared to controls, rising evidence that proximal tubular reabsorption of lithium was decreased. Tubular reabsorption of phosphate was not impaired. The decrease in glomerular filtration and renal perfusion during chronic treatment with CsA was accompanied by a reduced proximal reabsorptive capacity, as was shown by lithium clearance. Our data do not support the hypothesis that functional parameters of the proximal tubular system can be used as indicators of CsA-induced nephrotoxicity.
环孢素（CsA）的慢性肾毒性作用包括近端肾小管萎缩和空泡形成。本研究调查了CsA对接受CsA治疗患者的肾血流动力学和节段性电解质转运的影响。测定了菊粉清除率（CIn）和对氨基马尿酸（PAH）清除率（CPAH）；采用锂清除率方法并计算每毫升肾小球滤过液的肾小管磷酸盐重吸收（TP/CIn）来研究近端肾小管功能。对20例无肾脏疾病的患者进行了调查：10例因非肾脏移植接受CsA治疗（第1组）和10名健康志愿者（第2组）。将所得结果与20例肾移植受者的结果进行比较，其中10例接受CsA和甲基泼尼松龙治疗（第3组），10例接受硫唑嘌呤和甲基泼尼松龙治疗（第4组）。接受CsA治疗的患者CIn和CPAH明显受损。未观察到CsA诱导的锂清除率有明显损害。与各自的对照组相比，接受CsA治疗的患者锂的分数排泄略有增加。与对照组相比，移植受者的TP/CIn较低；未发现CsA诱导的磷酸盐重吸收受损。与对照组相比，锂的肾小管分数排泄略有增加，越来越多的证据表明近端肾小管对锂的重吸收减少。肾小管对磷酸盐的重吸收未受损。CsA慢性治疗期间肾小球滤过和肾灌注的降低伴随着近端重吸收能力的降低，锂清除率显示了这一点。我们的数据不支持近端肾小管系统功能参数可作为CsA诱导的肾毒性指标的假设。
