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Comment published on 17 April 2017, see Toxins 2017, 9(4), 142.

Open AccessReview
Toxins 2016, 8(12), 358; doi:10.3390/toxins8120358

Indoxyl Sulfate—Review of Toxicity and Therapeutic Strategies

The Departments of Medicine, VA Palo Alto HCS and Stanford University, Nephrology 111R, Palo Alto VAHCS, 3801 Miranda Ave., Palo Alto, CA 94304, USA
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Author to whom correspondence should be addressed.
Academic Editor: Raymond Vanholder
Received: 3 November 2016 / Revised: 24 November 2016 / Accepted: 28 November 2016 / Published: 30 November 2016
(This article belongs to the Special Issue Novel Issues in Uremic Toxicity)
View Full-Text   |   Download PDF [247 KB, uploaded 30 November 2016]

Abstract

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. View Full-Text
Keywords: indoxyl sulfate; dialysis; uremia indoxyl sulfate; dialysis; uremia
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Leong, S.C.; Sirich, T.L. Indoxyl Sulfate—Review of Toxicity and Therapeutic Strategies. Toxins 2016, 8, 358.

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