No change in impaired endothelial function after long-term folic acid therapy of hyperhomocysteinaemia in haemodialysis patients

Guldener, Coen van; Janssen, M. J. F. M.; Lambert, J.; Wee, Piet M. ter; Jakobs, Cornelis; Donker, A. J. M.; Stehouwer, Coen D.A.

doi:10.1093/ndt/13.1.106

Cited by 112 publications

(80 citation statements)

References 30 publications

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“…33 Although several investigators have demonstrated that flow-mediated vasodilation is impaired in patients with chronic hemodialysis, 13,14 we demonstrated, for the first time, that a single session of hemodialysis per se blunted endotheliumdependent vasodilation. In the present study, the increases in blood flow during reactive hyperemia were similar before and after hemodialysis, indicating that the amount of shear stress to the brachial artery during reactive hyperemia was comparable.…”

Section: Effect Of Hemodialysis On Endothelial Functionmentioning

confidence: 53%

“…[5][6][7][8][9] Endothelium-derived NO plays a crucial role not only in control of vascular tone of conduit arteries but also in antiatherosclerosis by several mechanisms, such as inhibition of platelet aggregation/adhesion or of smooth muscle cell proliferation. 10 -12 Recent reports demonstrated that NOdependent flow-mediated vasodilation is blunted in patients undergoing hemodialysis, 13,14 suggesting that the impaired bioactivity of endothelium-derived NO in the conduit artery may contribute to the progression of atherosclerosis in hemodialyzed patients.…”

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confidence: 99%

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Hemodialysis Impairs Endothelial Function via Oxidative Stress

et al. 2000

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Background-Patients who undergo hemodialysis experience accelerated atherosclerosis and premature death. Recent evidence suggests that endothelial dysfunction proceeds to and exacerbates atherosclerosis. It remains unknown whether hemodialysis per se causes endothelial dysfunction. Methods and Results-We evaluated endothelial function estimated by flow-mediated vasodilation during reactive hyperemia using high-resolution ultrasound Doppler echocardiography before and after a single session in patients on maintenance hemodialysis. Several studies have shown that the imbalance between pro-oxidant and antioxidant activities in hemodialyzed patients results in high oxidative stress, which causes lipid peroxidation and endothelial injury. Accordingly, we investigated the effects of antioxidative modification during hemodialysis on endothelial function using a vitamin E-coated cellulose membrane dialyzer. Nonspecific endothelium-independent vasodilation was measured after administration of a sublingual glyceryl trinitrate spray (0.3 mg). A single session of hemodialysis by noncoated dialyzer impaired flow-mediated vasodilation (PϽ0.05) associated with increased plasma levels of oxidized LDL (PϽ0.05), an index of oxidative stress. Hemodialysis by vitamin E-coated membrane prevented dialysis-induced endothelial dysfunction and increases in oxidized LDL. Plasma levels of oxidized LDL were inversely correlated with the magnitudes of flow-mediated vasodilation (rϭϪ0.53, PϽ 0.001). Hemodialysis by noncoated or vitamin E-coated membrane did not affect glyceryl trinitrate-induced endothelium-independent vasodilation. Conclusions-Our findings indicate that hemodialysis per se impairs endothelial function, possibly by increasing oxidative stress.

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Section: Effect Of Hemodialysis On Endothelial Functionmentioning

confidence: 53%

mentioning

confidence: 99%

Hemodialysis Impairs Endothelial Function via Oxidative Stress

et al. 2000

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“…Although no directly comparable studies have been conducted, a small openlabel trial of folic acid at doses up to 15 mg daily for 1 year in hemodialysis patients also showed no improvement in EDD or plasma vWF concentration. 19 However, in healthy BMI indicates body mass index; BP, blood pressure; GFR, glomerular filtration rate; and WHR, waist-to-hip ratio.…”

Section: Discussionmentioning

confidence: 99%

“…Although plasma homocysteine concentrations in nonuremic subjects can often be normalized by low doses of folic acid, 5 such reductions have not been consistently achieved with up to 15 mg of folic acid per day in patients with chronic renal failure. 4,6,19,22 The metabolism of homocysteine is also dependent on other micronutrients, including the B-group vitamins. However, correction of hyperhomocysteinemia in uremia has not been demonstrated with vitamins B 6 , B 12 , 6 serine, 23 or betaine.…”

Section: Discussionmentioning

confidence: 99%

Does Folic Acid Decrease Plasma Homocysteine and Improve Endothelial Function in Patients With Predialysis Renal Failure?

et al. 2000

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Background-Considerable evidence suggests that hyperhomocysteinemia is an independent vascular risk factor that promotes atherosclerosis by inducing endothelial dysfunction. Although folic acid reduces hyperhomocysteinemia, the effect on adverse vascular events is unknown. We hypothesized that in patients with chronic renal failure, a condition associated with both hyperhomocysteinemia and atherosclerosis, treatment with folic acid would improve endothelial function. Methods and Results-In a prospective, double-blind protocol, 100 patients (mean age 62 years, 67 men) with predialysis chronic renal failure were randomized to 5 mg folic acid or placebo daily for 12 weeks. Endothelial function was assessed by measuring (1) endothelium-dependent dilation of the brachial artery, (2)

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“…Endothelial dysfunction is a key process in atherosclerosis, which independently predicts CVD events (24) ; and it becomes progressively more common as renal function declines (25) . However, studies of supplementation with either 5 mg/d folic acid or 5 mg/d folic acid combined with 4 g/d betaine for 12 weeks, followed by either 1 or 5 mg/d folic acid for 40 weeks showed no improvement of endothelial function in patients on peritoneal dialysis or HD (26,27) . Another problem that complicates the interpretation of the literature on Hcy-lowering therapy is the lack of data supporting either an optimal dose of folic acid, an optimal target level of Hcy, or the required duration of intervention in order to see an effect.…”

Section: Studymentioning

confidence: 99%

Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials

et al. 2012

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The efficacy of homocysteine (Hcy)-lowering therapy in reducing the risk of CVD among patients with chronic kidney disease (CKD) remains controversial. We performed a meta-analysis to determine whether pooling the data from the few small randomised, controlled trials that address this topic would improve the statistical power of the analysis and resolve some of the inconsistencies in the results. Randomised, controlled clinical trials (RCT) were identified from MEDLINE, EMBASE, www.clinicaltrials.gov, the Cochrane Controlled Clinical Trials Register Database and Nephrology Filters. Independent extraction of articles was performed using predefined data fields. The primary outcome was relative risk (RR) of CVD, CHD, stroke and all-cause mortality for the pooled trials. A stratified analysis was planned, assessing the RR for cardiovascular events between the patients on and not on dialysis. Overall, ten studies met the inclusion criteria. The estimated RR were not significantly different for any outcomes, including CHD (RR 1·00, 95 % CI 0·75, 1·31, P ¼ 0·97), CVD (RR 0·94, 95 % CI 0·84, 1·05, P ¼ 0·30), stroke (RR 0·83, 95 % CI 0·57, 1·19, P ¼ 0·31) and all-cause mortality (RR 1·00, 95 % CI 0·92, 1·09, P ¼ 0·98). In the stratified analysis, the estimated RR were not significantly different for cardiovascular events regardless of dialysis or in combination with vitamin B therapy or the degree of reduction in Hcy levels. Our meta-analysis of RCT supports the conclusion that Hcy-lowering therapy was not associated with a significant decrease in the risk for CVD events, stroke and all-cause mortality among patients with CKD.Key words: CVD: Chronic kidney disease: Folic acid: Homocysteine-lowering therapy: Homocysteine: Meta-analyses CVD is the leading cause of mortality both among the general population and among patients with chronic kidney disease (CKD). The rate of mortality from CVD among patients on haemodialysis (HD) is 20-fold higher than that among the general population (1) , and impaired renal function per se is a very strong cardiovascular prognostic factor (2,3) . Therefore, much attention has been focused on managing risk factors to attempt to reduce the associated CVD risks, especially among patients with CKD. Elevated plasma total homocysteine (Hcy) has been proposed as a risk factor for cardiovascular morbidity and mortality in patients either with normal renal function or with CKD (4,5) . Among patients with CKD, plasma Hcy levels tend to increase with decreasing glomerular filtration rate (6) ; thus, hyperhomocysteinaemia may potentially further increase the risk of CVD in this special population. In the Cardiovascular Risk Extended Evaluation in Dialysis trial, investigators followed-up on 175 patients with kidney failure for 29 months and found that an increase in Hcy of 10 mmol/l was associated with a 20 % increased risk for CVD events (7) . In another study, Hcy was found to be a strong independent predictor of mortality among patients on HD with a 3 % increase in mortality for each 1 mmol...

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No change in impaired endothelial function after long-term folic acid therapy of hyperhomocysteinaemia in haemodialysis patients

Cited by 112 publications

References 30 publications

Hemodialysis Impairs Endothelial Function via Oxidative Stress

Hemodialysis Impairs Endothelial Function via Oxidative Stress

Does Folic Acid Decrease Plasma Homocysteine and Improve Endothelial Function in Patients With Predialysis Renal Failure?

Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials

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