Niwa T
Department of Clinical Laboratory and Nephrology, Nagoya University Branch Hospital, Japan.
Semin Nephrol. 1996 May;16(3):167-82.
A number of organic acids including phenols are accumulated in plasma of uremic patients because of reduced renal clearance. Some of them account for uremic problems such as reduced drug binding. Protein-bound organic acids such as hippuric acid, indoxyl sulfate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), are markedly accumulated in uremic plasma, and produce defective protein binding of drugs. CMPF is tightly bound to serum albumin, and thus cannot be removed by conventional hemodialysis, but continuous ambulatory peritoneal dialysis and protein-leaking hemodialysis can remove CMPF, leading to lower serum levels. Based on the findings that indoxyl sulfate stimulates the progression of chronic renal failure in rats, and that low-protein diet or oral sorbent exert protective effects on the progression of chronic renal failure and reduce the serum and urine levels of indoxyl sulfate, the author proposes a protein metabolite hypothesis that endogenous protein metabolites such as indoxyl sulfate play a significant role in the progression of chronic renal failure.
由于肾脏清除率降低，包括酚类在内的多种有机酸在尿毒症患者的血浆中蓄积。其中一些导致了尿毒症相关问题，如药物结合减少。与蛋白质结合的有机酸，如马尿酸、硫酸吲哚酚和3-羧基-4-甲基-5-丙基-2-呋喃丙酸（CMPF），在尿毒症血浆中显著蓄积，并导致药物的蛋白质结合缺陷。CMPF与血清白蛋白紧密结合，因此不能通过常规血液透析清除，但持续非卧床腹膜透析和蛋白渗漏血液透析可以清除CMPF，导致血清水平降低。基于硫酸吲哚酚刺激大鼠慢性肾衰竭进展的研究结果，以及低蛋白饮食或口服吸附剂对慢性肾衰竭进展具有保护作用并降低硫酸吲哚酚的血清和尿液水平的研究结果，作者提出了一种蛋白质代谢产物假说，即内源性蛋白质代谢产物如硫酸吲哚酚在慢性肾衰竭进展中起重要作用。
