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Toxins 2018, 10(6), 226; https://doi.org/10.3390/toxins10060226

Uremic Toxin Clearance and Cardiovascular Toxicities

1
The Departments of Medicine, VA Palo Alto Healthcare System, 111R, 3801 Miranda Ave., Palo Alto, CA 94304, USA
2
Division of Nephrology, Stanford University, 777 Welch Road, Suite DE, Palo Alto, CA 94304, USA
*
Author to whom correspondence should be addressed.
Received: 10 April 2018 / Revised: 25 May 2018 / Accepted: 31 May 2018 / Published: 2 June 2018
(This article belongs to the Special Issue Uremia and Cardiovascular Disease)
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Abstract

Uremic solutes contribute to cardiovascular disease in renal insufficiency. In this review we describe the clearance of selected uremic solutes, which have been associated with cardiovascular disease. These solutes—indoxyl sulfate (IS), p-cresol sulfate (PCS), phenylacetylglutamine (PAG), trimethylamine-n-oxide (TMAO), and kynurenine—exemplify different mechanisms of clearance. IS and PCS are protein-bound solutes efficiently cleared by the native kidney through tubular secretion. PAG and TMAO are not protein-bound but are also cleared by the native kidney through tubular secretion, while kynurenine is not normally cleared by the kidney. Increases in the plasma levels of the normally secreted solutes IS, PCS, TMAO, and PAG in chronic kidney disease (CKD) are attributable to a reduction in their renal clearances. Levels of each of these potential toxins are even higher in patients on dialysis than in those with advanced chronic kidney disease, which can be accounted for in part by a low ratio of dialytic to native kidney clearance. The rise in plasma kynurenine in CKD and dialysis patients, by contrast, remains to be explained. Our ability to detect lower levels of the potential uremic cardiovascular toxins with renal replacement therapy may be limited by the intermittency of treatment, by increases in solute production, and by the presence of non-renal clearance. Reduction in the levels of uremic cardiovascular toxins may in the future be achieved more effectively by inhibiting their production. View Full-Text
Keywords: Uremia; cardiovascular disease; dialysis Uremia; cardiovascular disease; dialysis
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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Mair, R.D.; Sirich, T.L.; Meyer, T.W. Uremic Toxin Clearance and Cardiovascular Toxicities. Toxins 2018, 10, 226.

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