Safirstein R, Miller P, Dikman S, Lyman N, Shapiro C
Am J Physiol. 1981 Aug;241(2):F175-85. doi: 10.1152/ajprenal.1981.241.2.F175.
We examined the effects of cisplatin (5 mg/kg BW) on renal function in rats. Three days after administration of cisplatin whole kidney clearance of inulin fell and 24-h urine volume increased. Maximal urine osmolality and papillary solute content were reduced. Superficial nephron glomerular filtration rate measured along the proximal tubule, where no leak of inulin could be demonstrated, was reduced in cisplatin-treated animals. Differences between superficial nephron glomerular filtration rate determined in proximal and distal tubules were greater in cisplatin-treated rats than in control rats. Neither a change in fluid or sodium movement along superficial nephrons nor a reduced early distal tubule transepithelial sodium gradient explain the polyuria. Urea was reabsorbed from, not added to, the loop fluid in cisplatin-treated animals. Morphologic changes were evident in the S3 segment of the proximal tubule in cisplatin-treated animals but the glomeruli were normal. Polyuria occurred despite diminished glomerular filtration rate in cisplatin nephrotoxicity. The diminished concentration of salt and urea in the papilla as a result of abnormal function of the collecting duct or pars recta portion of the proximal tubule contributed to the defect in concentrating ability.
我们研究了顺铂（5毫克/千克体重）对大鼠肾功能的影响。给予顺铂三天后，菊粉的全肾清除率下降，24小时尿量增加。最大尿渗透压和乳头溶质含量降低。在顺铂处理的动物中，沿近端小管测量的浅表肾单位肾小球滤过率降低，在该部位未发现菊粉泄漏。与对照大鼠相比，顺铂处理大鼠近端和远端小管中浅表肾单位肾小球滤过率的差异更大。沿浅表肾单位的液体或钠转运变化以及早期远端小管跨上皮钠梯度降低均不能解释多尿现象。在顺铂处理的动物中，尿素是从髓袢液中重吸收而非添加到髓袢液中。顺铂处理的动物近端小管S3段有明显的形态学变化，但肾小球正常。尽管顺铂肾毒性导致肾小球滤过率降低，但仍出现多尿。由于集合管或近端小管直部功能异常，乳头中盐和尿素浓度降低，导致浓缩能力缺陷。
