Blood levels of urea rise with progressive decline in kidney function. Older studies examining acute urea infusion suggested that urea was well-tolerated at levels 8–10× above normal values. More recent in vitro and in vivo work argue the opposite and demonstrate both direct and indirect toxicities of urea, which probably promote the premature aging phenotype that is pervasive in chronic kidney disease (CKD). Elevated urea at concentrations typically encountered in uremic patients induces disintegration of the gut epithelial barrier, leading to translocation of bacterial toxins into the bloodstream and systemic inflammation. Urea induces apoptosis of vascular smooth muscle cells as well as endothelial dysfunction, thus directly promoting cardiovascular disease. Further, urea stimulates oxidative stress and dysfunction in adipocytes, leading to insulin resistance. Finally, there are widespread indirect effects of elevated urea as a result of the carbamylation reaction, where isocyanic acid (a product of urea catabolism) alters the structure and function of proteins in the body. Carbamylation has been linked with renal fibrosis, atherosclerosis and anaemia. In summary, urea is a re-emerging Dark Force in CKD pathophysiology. Trials examining low protein diet to minimize accumulation of urea and other toxins suggest a clinical benefit in terms of slowing progression of CKD.
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January 2017
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Masson staining of rat liver specimens. Please see pp. 159-168 for more information. Image provided by Xujiong Li.
Review Article|
November 21 2016
Urea, a true uremic toxin: the empire strikes back
Wei Ling Lau;
Wei Ling Lau
*Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, U.S.A.
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Nosratola D. Vaziri
*Division of Nephrology and Hypertension, University of California Irvine, Orange, CA, U.S.A.
Correspondence: Nosratola D. Vaziri (email [email protected]).
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Publisher: Portland Press Ltd
Received:
March 14 2016
Revision Received:
September 12 2016
Accepted:
September 28 2016
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2016
Clin Sci (Lond) (2017) 131 (1): 3–12.
Article history
Received:
March 14 2016
Revision Received:
September 12 2016
Accepted:
September 28 2016
Citation
Wei Ling Lau, Nosratola D. Vaziri; Urea, a true uremic toxin: the empire strikes back. Clin Sci (Lond) 1 January 2017; 131 (1): 3–12. doi: https://doi.org/10.1042/CS20160203
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