Suppression of para-aminohippurate transport in the isolated perfused kidney by an inhibitor of protein binding in uremia.
Suppression of para-aminohippurate transport in the isolated perfused kidney by an inhibitor of protein binding in uremia.
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尿毒症中蛋白质结合抑制剂抑制离体灌注肾中对氨基马尿酸的转运。
DOI：
10.1016/s0272-6386(84)80046-3
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Stanfel,LA
中科院分区：
文献类型：
--
作者：
Depner,TA;Sanaka,T;Stanfel,LA
晚期肾衰竭患者的血清中含有抑制小配体与白蛋白结合的物质。将先前在大鼠肾切片中显示可抑制对氨基马尿酸盐（PAH）转运的可提取白蛋白（IX）结合抑制剂添加到体外灌注大鼠肾脏中，以研究对完整器官中有机酸转运的影响。向灌注液中加入浸提液后，全肾PAH分泌立即显著减少。加入人尿毒症胸膜渗出液浸提液后，PAH平均清除率平均下降60% ± 7%，加入正常人尿液相似制备的浸提液后，PAH平均清除率平均下降62% ± 6%。菊粉清除率、血管阻力、尿流量或钠重吸收分数无变化。当向灌注液中加入牛血清白蛋白（4.0 g/dL）时，效果显著，清除率下降66% ± 7%。在90分钟的体外灌注期间，对照显示PAH或菊粉清除率没有变化。在向灌注液中加入抑制剂后几分钟内，尿液的紫外线（UV）吸光度增加，表明提取物的主要部分由肾小管分泌。20 - 40分钟后，在大多数肾脏中观察到PAH清除率部分恢复，在一些肾脏中几乎完全恢复。通过向灌注液中加入24 mg/dL（1.2 mmol/L）马尿酸盐复制抑制作用。这些研究结果表明，有机酸分泌的整个哺乳动物肾脏可以特异性和可逆性抑制部分纯化的蛋白结合抑制剂在尿毒症。马尿酸盐和正常尿液提取物的类似作用表明，尿毒症患者体液中积累的几种蛋白质结合的有机酸可能是这两种现象的原因。
Serum from patients with advanced renal failure contains substances that inhibit binding of small ligands to albumin. The extractable inhibitors of binding to albumin (IX), which were previously shown in rat kidney slices to inhibit para-aminohippurate (PAH) transport, were added to the in vitro perfused rat kidney in an attempt to investigate effects on organic acid transport in the intact organ. Following addition of extract to the perfusate there was an immediate and profound decrease in whole kidney PAH secretion. Mean PAH clearance fell an average of 60% ± 7% after addition of extract from human uremic pleural exudate and an average of 62% ± 6% after addition of similarly prepared extract from normal human urine. There was no change in inulin clearance, vascular resistance, urine flow, or fractional reabsorption of sodium. The effect was shown to be as marked when bovine serum albumin (4.0 g/dL) was added to the perfusate, clearances falling 66% ± 7%. Controls showed no change in PAH or inulin clearance during 90 minutes of in vitro perfusion. An increase in ultraviolet (UV) absorbance by the urine within minutes after addition of inhibitor to the perfusate suggested tubular secretion of a major portion of the extract. Partial recovery of PAH clearance was observed after 20 to 40 minutes in most kidneys and near complete recovery occurred in some kidneys. The inhibitory effect was duplicated by addition of hippurate at 24 mg/dL (1.2 mmol/L) to the perfusate. These findings show that organic acid secretion by whole mammalian kidneys can be specifically and reversibly suppressed by partially purified inhibitors of protein binding in uremia. Similar effects by hippurate and by an extract of normal urine suggest that several protein-bound organic acids accumulating in body fluids of uremic patients may account for both phenomena.
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