The effect of L-arginine on arterial stiffness and oxidative stress in chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a growing problem worldwide. The disproportionate increase in the burden of cardiovascular disease in patients with CKD may be significantly contributed by nontraditional risk factors. Increased arterial stiffness has been recognized as an important player in contributing to this morbidity and mortality. The aim of this study was to report the effect of L-arginine on arterial stiffness and oxidative stress in patients with CKD. Thirty patients with stage II to IV CKD were administered 9 g of L- arginine per day orally for a period of 12 weeks. The parameters evaluated at baseline, at 8 weeks, and at the end of 12 weeks were serum nitric oxide (NO), carotid.femoral pulse wave velocity (cf PWV), and radial artery pulse wave analysis which included aortic augmentation pressure (AP), aortic augmentation index (AIx), aortic augmentation index at heart rate of 75 bpm, subendocardial viability ratio, radial pressures, and central aortic pressure. Serum levels of NO and malondialdehyde (MDA) were estimated at baseline and at the end of 12 weeks. The control group was composed of age- and sex-matched healthy individuals. Twenty-five patients completed the study. Two patients were lost to follow.up; three patients developed adverse events and were excluded. Baseline NO levels were low (13.55 ± 7.49 μM/L) in all the subjects. Administration of L-arginine resulted in improvement in the carotid-radial PWV (m/s) (10.08 ± 1.72 at baseline to 8.56 ± 1.16 by 12 weeks; P < 0.001), cf PWV (m/s) (13.06 ± 2.65 at baseline to 10.62 ± 1.93 at 12 weeks; P < 0.001), Aortic Augmentation Index (%) (32 ± 10.34 at baseline to 17.84 ± 8.05 at 12 weeks; P < 0.001), aortic augmentation pressure (mm of Hg) (14.03 ± 6.53 at baseline to 7.12 ± 3.85 at 12 weeks; P < 0.001), and NO (μM/L) (13.55 ± 7.49 at baseline to 30.22 ± 9.8 at 12 weeks; P < 0.001). There was no significant change in the levels of MDA (nanomol/ml) (20.0 ± 10.14 at baseline and 19.16 ± 9.36 at 12 weeks; P = ns). In conclusion, PWV, an indicator of arterial stiffness, is greatly increased even in the early stages of CKD. Supplementation of L-arginine is a safe, well-tolerated, and effective way of improving endothelial dysfunction in patients with CKD.

Oxidative stress in chronic kidney disease

“…Several uremic toxins such as AGEs, IS, and p-cresyl sulfate and eNOS uncoupling have been shown to induce arterial stiffness through increased oxidative stress [165][166][167][168][169]. In a small study, supplementation of Larginine was shown to be a safe, well-tolerated, and effective way of improving endothelial dysfunction in patients with CKD [169].…”

Dietary Antioxidant Supplements and Uric Acid in Chronic Kidney Disease: A Review

“…L -Arginine is an amino acid with antioxidant properties, scavenging ROS directly, and acting as a substrate for ΝO synthesis. Several investigators showed both, in uremic animal models and humans that supplementation of l -arginine successfully reduces OS status and inhibits vascular calcification, through upregulation of NO [125,126]. Sanchez-Lozada et al investigated the possible effect of chronic and acute supplementation of l -arginine on the structural and functional changes in renal hemodynamics that was caused by induced hyperuricemia in rats [54].…”

Arterial Stiffness: A Nexus between Cardiac and Renal Disease

“…Fourth, uric acid may accelerate AS development. Mechanisms implicated for increased AS in patients with uricemia include chronic fluid overload, arterial calcifications, inflammation, sympathetic nervous system overactivity, activation of RAAS, increased lipid oxidation, and abnormalities in the NO system [49]. Thus, this bidirectionality between kidney disease and AS sets up a potentially vicious cycle, wherein a primary abnormality in either aorta or kidney function could lead to accelerated deterioration in the structure and function of both organs.…”