Oxidative Stress and Asymmetric Dimethylarginine Are Associated with Cardiovascular Complications in Hemodialysis Patients: Improvements by <i>L</i>-Arginine Intake

Abstract

Background/Aim: High incidence of cardiovascular disease (CVD) in chronic kidney disease (CKD) patients is a result of an interlaced relation between oxidative stress, endothelial dysfunction (ED) and inflammation. This study tries to investigate the development of these processes in CKD patients receiving conservative treatment or on hemodialysis (HD). We also examined the modulating effect of oral L-arginine in HD patients having CVD. Methods: The study included 12 healthy volunteers and 63 renal patients divided into 15 renal impairment, 18 HD free of CVD, and 30 HD suffering from CVD (HD+CVD). Of the latter, 15 patients were given oral L-arginine (15 g/day, 5 g t.i.d.) for 1 month. Blood levels of asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), and homocysteine and myeloperoxidase activity (MPO) were estimated. Results: ADMA, MDA and homocysteine were significantly elevated in renal impairment group. HD and HD+CVD patients experienced higher levels, along with high MPO activity. Significant reduction by 21, 46, 11, and 26%, respectively, in the aforementioned parameters was observed in HD+CVD patients following L-arginine intake. Conclusion:We recommend considering ADMA, MDA, homocysteine and MPO as potentially important cardiovascular risk factors in CKD patients, and focus the attention to the cardiovascular advantages of L-arginine in these patients.

Multiple Antioxidants and L-Arginine Modulate Inflammation and Dyslipidemia in Chronic Renal Failure Rats

“…[58] This is supported by reduced sICAM-1 levels in association with increased NO levels in treated rats in the current study. Furthermore, L-arginine may decrease the oxidative stress [53] ; this effect is supported by previous reports of decreased urinary excretion of 8-iso-prostaglandin F 2a (PGF 2a ), a non-invasive marker of oxidative stress in vivo after L-arginine treatment. [59] Meanwhile, the blood pressure-lowering effect of the antioxidant mixture used in the current study could be due to decreased NO breakdown, potentially related to lower release of ROS.…”

“…Other than its ability to increase NO production, Larginine is suggested to decrease the levels of the NOS antagonist ADMA, homocysteine, and malondialdehyde (MDA) and myeloperoxidase (MPO) activity in hemodialysis patients. [53] Clinical and experimental evidence suggests that the enzymatic activity of NOS is regulated by the ratio between the concentration of L-arginine (the natural substrate) and that of ADMA (the endogenous inhibitor). [54] Abbreviations: Control = sham operated healthy rats receiving no treatment, RMR = renal mass reduction rats without treatment, RMR+L-arg = renal mass reduction rats receiving L-arginine treatment, RMR+antiox = renal mass reduction rats receiving antioxidants treatment, RMR+antiox+L-arg = renal mass reduction rats receiving L-arginine and antioxidant treatment.…”

Asymmetric dimethyl arginine levels in chronic hemodialysis patients

“…This result is consistent with the previous similar studies in the literature regarding ADMA levels in ESRD patients (9,14,15). Circulating levels of ADMA had a positive correlation with levels of CRP.…”

hsCRP, sICAM-1 and TAFI in Hemodialysis Patients: Linking Inflammation and Hypofibrinolysis to Cardiovascular Events

“…In a recent article from our laboratory [18] , we provided evidence that oxidative stress and asymmetric dimethylarginine are associated with cardiovascular complications in HD patients and that administration of oral L -arginine (15 g/day) significantly improved the cardiovascular markers profile of those patients. In continuation, this study aims to unravel other pathways that play a role in the development of CVD in HD patients, including inflammation and hypofibrinolysis, and to test the therapeutic value of L -arginine in reducing the progression of these cascades.…”