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139 - Uremia
- from PART III - VASCULAR BED/ORGAN STRUCTURE AND FUNCTION IN HEALTH AND DISEASE
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- By Jan T. Kielstein, Medical School of Hannover, Germany; Stanford University School of Medicine, California, Danilo Fliser, Medical School of Hannover, Germany;
- Edited by William C. Aird, Harvard University, Massachusetts
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- Book:
- Endothelial Biomedicine
- Published online:
- 04 May 2010
- Print publication:
- 03 September 2007, pp 1278-1286
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- Chapter
- Export citation
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Summary
The uremic syndrome can be defined as the deterioration of multiple biochemical and physiological functions in parallel with progressive renal failure. A myriad of compounds, termed uremic toxins, lead to a complex and variable symptomatology – the uremic syndrome. One hallmark of this syndrome is the rapid development of cardiovascular disease. A cornerstone in the complex pathogenesis of this cardiorenal interaction is the endothelium, because it controls many aspects of vascular function. The endothelium produces a wide range of regulatory molecules that, in health, provide a carefully balanced antiatherogenic environment. In contrast, endothelial dysfunction has been demonstrated repeatedly in renal failure, is present in the absence of anatomically obvious disease, and appears to be useful in the prediction of morbidity and mortality in other cardiovascular risk groups. One of the most important and intensively studied mediators of endothelial function is nitric oxide (NO). Numerous preclinical and clinical studies have shown that NO bioavailability is reduced in chronic kidney disease (CKD). NO deficiency contributes to the progressive nature of CKD, endothelial dysfunction, and associated risk for cardiovascular events. Mechanisms of NO deficiency are likely multifactorial. They include substrate limitation, competitive inhibition of NO synthase (NOS) by endogenous NOS inhibitors, and premature quenching of NO by free radicals. Recent evidence points to an important role for the NOS inhibitor, asymmetric dimethylarginine (ADMA). This compound has a wide range of actions that are consistent not only with its role in uremia pathophysiology but also as a common pathway through which cardiovascular risk factors exert their deleterious effects. Unlike other uremic toxins, it also predicts for progression of renal disease.