***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Haemodialysis ( HD ) is associated with the acute loss through the dialysis membrane of biochemical factors either enhancing [ folic acid ( F ) ] or impairing [ asymmetric dimethylarginine ( ADMA ) ] arterial function . Changes in these opposing factors might explain the absence of significant modifications in arterial function during HD . We speculated that intra-HD , instead of pre-HD , F administration would provide beneficial effects on arterial wave reflections and endothelial function by preventing HD-induced F loss . METHODS Arterial wave reflections [ augmentation index ( AIx ) , pulse-wave analysis ] , endothelium-dependent vasodilation ( salbutamol-mediated changes in AIx ) and plasma concentrations of F and ADMA were measured pre-HD and end-HD in 10 patients ( age 67.7 + /- 10.3 years ) . Each subject received F 5 mg either pre-HD or intra-HD in two separate studies 2 - 4 weeks apart , in an open-label r and omized cross-over trial . RESULTS Pre-HD F administration did not prevent significant reductions in F during HD ( end-HD vs. pre-HD , -865 + /- 465 nmol l(-1 ) , P < 0.001 ) , but no significant changes in AIx ( + 1.4 + /- 5.7 % ) or salbutamol-mediated AIx modifications ( + 0.4 + /- 5.5 % ) were observed . By contrast , intra-HD F administration was associated with significant increases in F ( + 298 + /- 283 nmol l(-1 ) , P = 0.010 ) and a significant reduction of AIx ( -4.7 + /- 7.2 % , P = 0.013 ) , but no effects on salbutamol-mediated AIx changes ( + 1.5 + /- 4.4 % ) . There was a trend towards greater HD-induced reductions in plasma ADMA concentrations with intra-HD F administration ( P = 0.066 ) . CONCLUSIONS Intra-HD F administration reduces arterial wave reflections but not endothelial function during HD . Given the prognostic significance of arterial wave reflections in HD patients , the timing of F administration is important in the design of interventional trials in this cohort Background —Increased oxidative stress , elevated plasma homocysteine concentration , increased pulse pressure , and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure . Methods and Results —We investigated the metabolic and hemodynamic effects of intravenous administration of acetylcysteine , a thiol-containing antioxidant , during a hemodialysis session in a prospect i ve , r and omized , placebo-controlled crossover study in 20 patients with end-stage renal failure . Under control conditions , a hemodialysis session reduced plasma homocysteine concentration to 58±22 % predialysis ( mean±SD ) , whereas in the presence of acetylcysteine , the plasma homocysteine concentration was significantly more reduced to 12±7 % predialysis ( P < 0.01 ) . The reduction of plasma homocysteine concentration was significantly correlated with a reduction of pulse pressure . A 10 % decrease in plasma homocysteine concentration was associated with a decrease of pulse pressure by 2.5 mm Hg . Analysis of the second derivative of photoplethysmogram waveform showed changes of arterial wave reflectance during hemodialysis in the presence of acetylcysteine , indicating improved endothelial function . Conclusions —Acetylcysteine-dependent increase of homocysteine removal during a hemodialysis session improves plasma homocysteine concentration , pulse pressure , and endothelial function in patients with end-stage renal failure BACKGROUND Hyperhomocysteinaemia is a putative risk factor for atherothrombotic cardiovascular disease in the haemodialysis population .  High-dose vitamin B therapy does not entirely normalize elevated plasma total homocysteine ( tHcy ) levels in haemodialysis patients . Alternative therapies to reduce tHcy further are therefore required . Modifications of the dialysis regimen may result in a better removal of Hcy . We examined the effect of dialyser membrane pore size on tHcy levels in vitamin-replete chronic haemodialysis patients . METHODS Forty-five haemodialysis patients were dialysed during 4 weeks with a low-flux , a high-flux and a super-flux membrane , in r and om order . Pre-dialysis  tHcy  was determined at baseline and every 4 weeks . In 18 patients , plasma tHcy before and after dialysis and dialysate tHcy concentrations were measured . RESULTS Pre-dialysis tHcy decreased significantly during 4 weeks super-flux dialysis ( -14.6 + /- 2.8 % ) , whereas it remained stable during high-flux ( + 0.5 + /- 2.4 % ) and low-flux dialysis ( + 1.7 + /- 3.2 % ) . The homocysteine reduction ratio was not different for the three membranes : 0.39 + /- 0.03 for the super-flux , 0.47 + /- 0.02 for the high-flux and 0.39 + /- 0.02 for the low-flux dialyser . The amount of Hcy recovered in the dialysate during a single dialysis session was also similar : 117.5 + /- 3.6 micro mol during super-flux , 95.3 + /- 11.5 micro mol during high-flux and 116.5 + /- 11.6 micro mol during low-flux dialysis . CONCLUSION Super-flux dialysis significantly lowers tHcy in chronic haemodialysis patients . Improved removal of middle-molecule uraemic toxins with inhibitory effects on Hcy-metabolizing enzymes , rather than better dialytic clearance of Hcy itself , may explain the beneficial effect of the super-flux membrane BACKGROUND Patients with chronic kidney disease ( CKD ) have an increased risk of cardiovascular disease ( CVD ) . Preliminary evidence suggests a role for global DNA hypomethylation in the pathogenesis of atherosclerotic complications in CKD . The aims of this study in patients with stage 2 - 4 CKD were ( 1 ) to assess the association between renal function and DNA methylation , ( 2 ) to assess the association between DNA methylation and two markers of atherosclerosis [ common carotid intima-media thickness ( CCA-IMT ) ] and brachial artery endothelium-dependent , flow-mediated dilatation ( BA-FMD ) and ( 3 ) to examine the effect of a multi-step treatment strategy on DNA methylation . METHODS In the Anti-Oxidant Therapy In Chronic Renal Insufficiency study ( ATIC- study ) , 93 patients with stage 2 - 4 CKD were included . In a r and omized , double-blind , placebo-controlled design , the treatment group received pravastatin to which vitamin E was added after 6 months and homocysteine-lowering B-vitamin therapy after another 6 months .  DNA methylation was assessed using t and em mass spectrometry . CCA-IMT and BA-FMD were assessed using B-mode ultrasonography . RESULTS At baseline , global DNA methylation was not associated with the estimated glomerular filtration rate ( P = 0.32 ) or with CCA-IMT ( P = 0.62 ) or BA-FMD ( P = 0.51 ) . No effect of the treatment strategy including B-vitamin on global DNA methylation was found either in the total study group or within separate strata of homocysteine concentration and renal function . CONCLUSION In patients with stage 2 - 4 CKD , global DNA methylation is not associated with renal function or with CCA-IMT or BA-FMD . A treatment strategy that includes B-vitamins did not alter global DNA methylation in these patients . These data do not support the role of DNA hypomethylation in CKD-associated vascular disease in patients with stage 2 - 4 CKD The Homocysteine Study ( HOST ) Veterans Affairs Cooperative Studies Program No. 453 , is a prospect i ve , r and omized , two arm , double blind study of patients with end stage renal disease ( ESRD ) or advanced chronic kidney disease ( ACKD , defined as an estimated creatinine clearance of 30 ml/min or less ) . Its primary objective is to determine whether administration of high doses of three vitamins , folic acid , vitamin B6 and vitamin B12 , to lower the high plasma homocysteine levels , will reduce all cause mortality . The secondary objectives are to examine whether the treatment lowers the incidence of myocardial infa rct ion , stroke , amputation of a lower extremity , a composite of death and the foregoing three events , the plasma homocysteine level , and , in  ESRD patients undergoing hemodialysis , thrombosis of the vascular access . A unique feature of this trial is that after initial evaluation at enrollment and one return visit the follow up is exclusively by phone ( or , if necessary , by mail ) . The subject is contacted every three months throughout the duration of the study from a central location . The study drug is shipped to the patient from a central location rather supplied locally . In a two year enrollment period , 2006 patients are to be enrolled . The duration of the observation period is four to six years . Data will be stored and analyzed at a coordinating center . The study design has the power to detect a reduction in all cause mortality rate of 17 % . Issues related to the unique features of the design of this study are discussed 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 prospect i ve , double-blind protocol , 100 patients ( mean age 62 years , 67 men ) with predialysis chronic renal failure were r and omized 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 ) combined serum nitrite/nitrate concentrations , and ( 3 ) plasma von Willebr and factor concentration . Baseline characteristics of the 2 groups were similar . At the end of the study , both serum and red cell folate concentrations were greater in the folic acid group than the placebo group [ mean ( 95 % CI ) 39.0 ( 29.8 to 51.0 ) versus 7.7 ( 6.6 to 8.9 ) microg/L and 739 ( 613 to 891 ) versus 220 ( 184 to 262 ) microg/L , respectively ; both P<0.001 ] . Despite a reduction in hyperhomocysteinemia in the folic acid group compared with the placebo group [ 15.1 ( 14.1 to 16.2 ) versus 20.1 ( 18.2 to 22.2 ) micromol/L ; P<0.001 ] , there were no significant differences in endothelium-dependent dilation , combined serum nitrite/nitrate concentrations , or plasma von Willebr and factor concentration between the 2 groups . CONCLUSIONS High-dose folic acid lowers but fails to normalize hyperhomocysteinemia in patients with predialysis chronic renal failure . This was not accompanied by an improvement of endothelial function and suggests that treatment with folic acid may not reduce the burden of vascular disease in uremia BACKGROUND The hyperhomocysteinemia found in most hemodialysis patients is refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid ( FA ) . We evaluated whether a high-dose L-folinic acid-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients , as suggested by a recent uncontrolled report . METHODS We block-r and omized 48 chronic , stable hemodialysis patients based on their screening predialysis tHcy levels , sex , and dialysis center into two groups of 24 subjects treated for 12 weeks with oral FA at 15 mg/day or an equimolar amount ( 20 mg/day ) of oral L-folinic acid ( FNA ) [ L-5-formyltetrahydrofolate ] . All 48 subjects also received 50 mg/day of oral vitamin B6 and 1.0 mg/day of oral vitamin B12 . RESULTS The mean percentage ( % ) reductions ( with 95 % CIs ) in predialysis tHcy were not significantly different [ FNA = 22.1 % ( 11.8 to 31.4 % ) , FA = 20.7 % ( 11.7 to 30.5 % ) , P = 0.950 by paired t test ] . Final on-treatment values ( mean with 95 % CI ) were as follows : FNA , 15.9 micromol/L ( 14.0 to 18.0 ) ; FA , 16.9 micromol 
    Output:
    
Homocysteine-lowering therapy had little or no effect on all-cause mortality or any other of this review 's secondary outcomes .
Homocysteine-lowering therapies were not found to reduce mortality ( cardiovascular and all-cause ) or cardiovascular events among people with ESKD