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      Peripheral Vascular Dysfunction in Chronic Kidney Disease

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      Cardiology Research and Practice
      SAGE-Hindawi Access to Research

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          Abstract

          There is an increased prevalence of cardiovascular disease- (CVD-) related mortality in patients with chronic kidney disease (CKD). Endothelial dysfunction is a primary event in the development of atherosclerosis and hypertension and likely contributes to the elevated cardiovascular risk in CKD. Endothelial dysfunction has been shown to occur in the peripheral vasculature of patients with both severe and moderate CKD. Mechanisms include oxidative stress, L-arginine deficiency, and elevated plasma levels of ADMA. Interventions designed to restore vascular function in patients with CKD have shown mixed results. Evidence from cell culture studies suggest that the accumulation of uremic toxins inhibits L-arginine transport and reduces nitric oxide production. The results of these studies suggest that endothelial dysfunction may become less reversible with advancing kidney disease. The purpose of this paper is to present the current literature pertaining to potential mechanisms of peripheral vascular dysfunction in chronic kidney disease and to identify possible targets for treatment.

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          Most cited references93

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          Endothelium-derived relaxing factor produced and released from artery and vein is nitric oxide.

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            Vascular endothelial cells synthesize nitric oxide from L-arginine.

            Nitric oxide (NO) released by vascular endothelial cells accounts for the relaxation of strips of vascular tissue and for the inhibition of platelet aggregation and platelet adhesion attributed to endothelium-derived relaxing factor. We now demonstrate that NO can be synthesized from L-arginine by porcine aortic endothelial cells in culture. Nitric oxide was detected by bioassay, chemiluminescence or by mass spectrometry. Release of NO from the endothelial cells induced by bradykinin and the calcium ionophore A23187 was reversibly enhanced by infusions of L-arginine and L-citrulline, but not D-arginine or other close structural analogues. Mass spectrometry studies using 15N-labelled L-arginine indicated that this enhancement was due to the formation of NO from the terminal guanidino nitrogen atom(s) of L-arginine. The strict substrate specificity of this reaction suggests that L-arginine is the precursor for NO synthesis in vascular endothelial cells.
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              Effect of allopurinol in chronic kidney disease progression and cardiovascular risk.

              Hyperuricemia is associated with hypertension, inflammation, renal disease progression, and cardiovascular disease. However, no data are available regarding the effect of allopurinol in patients with chronic kidney disease. We conducted a prospective, randomized trial of 113 patients with estimated GFR (eGFR) <60 ml/min. Patients were randomly assigned to treatment with allopurinol 100 mg/d (n = 57) or to continue the usual therapy (n = 56). Clinical, biochemical, and inflammatory parameters were measured at baseline and at 6, 12, and 24 months of treatment. The objectives of study were: (1) renal disease progression; (2) cardiovascular events; and (3) hospitalizations of any causes. Serum uric acid and C-reactive protein levels were significantly decreased in subjects treated with allopurinol. In the control group, eGFR decreased 3.3 +/- 1.2 ml/min per 1.73 m(2), and in the allopurinol group, eGFR increased 1.3 +/- 1.3 ml/min per 1.73 m(2) after 24 months. Allopurinol treatment slowed down renal disease progression independently of age, gender, diabetes, C-reactive protein, albuminuria, and renin-angiotensin system blockers use. After a mean follow-up time of 23.4 +/- 7.8 months, 22 patients suffered a cardiovascular event. Diabetes mellitus, previous coronary heart disease, and C-reactive protein levels increased cardiovascular risk. Allopurinol treatment reduces risk of cardiovascular events in 71% compared with standard therapy. Allopurinol decreases C-reactive protein and slows down the progression of renal disease in patients with chronic kidney disease. In addition, allopurinol reduces cardiovascular and hospitalization risk in these subjects.
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                Author and article information

                Journal
                Cardiol Res Pract
                CRP
                Cardiology Research and Practice
                SAGE-Hindawi Access to Research
                2090-0597
                2011
                24 May 2011
                : 2011
                : 267257
                Affiliations
                Department of Kinesiology & Applied Physiology, University of Delaware, 541 South College Avenue, Newark, DE 19716, USA
                Author notes
                *David G. Edwards: dge@ 123456udel.edu

                Academic Editor: Abarmard Maziar Zafari

                Article
                10.4061/2011/267257
                3103875
                21637718
                29c3cee5-5b39-4085-98a1-72c6e9cefc7c
                Copyright © 2011 C. R. Martens and D. G. Edwards.

                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.

                History
                : 24 December 2010
                : 15 March 2011
                Categories
                Review Article

                Cardiovascular Medicine
                Cardiovascular Medicine

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