Indoxyl Sulfate-Review of Toxicity and Therapeutic Strategies.
Indoxyl Sulfate-Review of Toxicity and Therapeutic Strategies.
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DOI：
10.3390/toxins8120358
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发表时间：
2016-11-30
期刊：
影响因子：
4.2
通讯作者：
Sirich TL
中科院分区：
文献类型：
--
作者：
Leong SC;Sirich TL
硫酸吲哚酚是一种广泛研究的尿毒症溶质。它是一种小分子，90%以上与血浆蛋白结合。硫酸吲哚酚是由结肠微生物分解色氨酸而得。肾脏通过肾小管分泌实现硫酸吲哚酚的高清除率，这是血液透析无法复制的功能。血液透析的清除率受到蛋白质结合的限制，因为只有游离的、未结合的溶质才能扩散穿过膜。由于透析清除率远低于肾脏清除率，因此硫酸吲哚酚在血液透析患者中蓄积至相对较高的血浆水平。硫酸吲哚酚最常被认为是肾脏疾病进展和血管疾病的促成因素。研究表明，硫酸吲哚酚对骨骼和中枢神经系统也有不良影响。大多数研究评估了培养细胞和动物模型中的毒性。对人类的毒性尚未得到证实，因为大多数数据来自相关研究。这些毒性数据虽然不确定，但已促使人们努力通过透析和非透析方法降低硫酸吲哚酚的血浆水平。最大的随机试验显示AST-120对肾脏疾病进展无益处。还没有试验测试心血管或死亡率的好处。如果没有这样的试验，硫酸吲哚酚的毒性就不能确定。
Indoxyl sulfate is an extensively studied uremic solute. It is a small molecule that is more than 90% bound to plasma proteins. Indoxyl sulfate is derived from the breakdown of tryptophan by colon microbes. The kidneys achieve high clearances of indoxyl sulfate by tubular secretion, a function not replicated by hemodialysis. Clearance by hemodialysis is limited by protein binding since only the free, unbound solute can diffuse across the membrane. Since the dialytic clearance is much lower than the kidney clearance, indoxyl sulfate accumulates to relatively high plasma levels in hemodialysis patients. Indoxyl sulfate has been most frequently implicated as a contributor to renal disease progression and vascular disease. Studies have suggested that indoxyl sulfate also has adverse effects on bones and the central nervous system. The majority of studies have assessed toxicity in cultured cells and animal models. The toxicity in humans has not yet been proven, as most data have been from association studies. Such toxicity data, albeit inconclusive, have prompted efforts to lower the plasma levels of indoxyl sulfate through dialytic and non-dialytic means. The largest randomized trial showed no benefit in renal disease progression with AST-120. No trials have yet tested cardiovascular or mortality benefit. Without such trials, the toxicity of indoxyl sulfate cannot be firmly established.
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