Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy

House, Andrew A.; Eliasziw, Misha; Cattran, Daniel C.; Churchill, David; Oliver, Matthew J.; Fine, Adrian; Dresser, George K.; Spence, J. David

doi:10.1001/jama.2010.490

Cited by 269 publications

(170 citation statements)

References 34 publications

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“…The final fourteen RCT enrolled 39 420 patients. Among them, seven were included in the without folate fortification subgroup (28)(29)(30)(31)(32)(33)(34) , four were included in the with folate fortification subgroup (35)(36)(37)(38) and three were included in the partial folate fortification subgroup (39)(40)(41) . The screening process of potential articles is summarized in a flowchart (Fig.…”

Section: Resultsmentioning

confidence: 99%

The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis

Zeng

Yang

et al. 2014

Public Health Nutr.

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Objective: Folate and vitamin B 12 are two vital regulators in the metabolic process of homocysteine, which is a risk factor of atherothrombotic events. Low folate intake or low plasma folate concentration is associated with increased stroke risk. Previous randomized controlled trials presented discordant findings in the effect of folic acid supplementation-based homocysteine lowering on stroke risk. The aim of the present review was to perform a meta-analysis of relevant randomized controlled trials to check the how different folate fortification status might affect the effects of folic acid supplementation in lowering homocysteine and reducing stroke risk. Design: Relevant randomized controlled trials were identified through formal literature search. Homocysteine reduction was compared in subgroups stratified by folate fortification status. Relative risks with 95 % confidence intervals were used as a measure to assess the association between folic acid supplementation and stroke risk. Setting: The meta-analysis included fourteen randomized controlled trials, Subjects: A total of 39 420 patients. Results: Homocysteine reductions were 26·99 (SD 1·91) %, 18·38 (SD 3·82) % and 21·30 (SD 1·98) %, respectively, in the subgroups without folate fortification, with folate fortification and with partial folate fortification. Significant difference was observed between the subgroups with folate fortification and without folate fortification (P = 0·05). The relative risk of stroke was 0·88 (95 % CI 0·77, 1·00, P = 0·05) in the subgroup without folate fortification, 0·94 (95 % CI 0·58, 1·54, P = 0·82) in the subgroup with folate fortification and 0·91 (95 % CI 0·82, 1·01, P = 0·09) in the subgroup with partial folate fortification. Conclusions: Folic acid supplementation might have a modest benefit on stroke prevention in regions without folate fortification.

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Section: Resultsmentioning

confidence: 99%

The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis

Zeng

Yang

et al. 2014

Public Health Nutr.

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“…Wrone et al (13) Righetti et al (14) Zoungas et al (12) House et al (21) Heinz et al (22) Overall 0·159537 One report demonstrated that endothelial cells can develop abnormal vasoreactivity and may adopt a prothrombotic phenotype and secrete leucocyte chemotactic factors, adhesion molecules and inflammatory cytokines when exposed to elevated Hcy (23) . 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) .…”

Section: Studymentioning

confidence: 99%

“…Also, to the best of our knowledge, there are no studies that have determined a threshold value for Hcy level for effective prevention of cardiovascular events in the general population or in patients with CKD. Observational data in a meta-analysis show that a 25 % reduction in Hcy was associated with a 32 % lower risk of CVD among Study Righetti et al (16) Wrone et al (13) Righetti et al (14) Zoungas et al (12) Jamison et al (20) Nanayakkara et al (18) Vianna et al (17) Mann et al (19) House et al (21) Heinz et al (22) Overall 0·074931 …”

Section: Studymentioning

confidence: 99%

“…Wrone et al (13) Zoungas et al (12) Righetti et al (14) Jamison et al (20) Heinz et al (22) House et al (21) Overall 0·021215 women and a 15 % lower risk among men (29) . However, the reported decreases in Hcy levels vary substantially; and the ten papers in our meta-analysis reported a wide range of Hcy-lowering from 8·9 % to 53·8 %, which is consistent with the observed range of decrease in patients without CKD.…”

Section: Studymentioning

confidence: 99%

“…It has been proposed that the mutant TT genotype at nucleotide 677 of the gene regulating methylenetetrahydrofolate reductase activity is associated with increased Hcy levels and increased mortality in general and CKD populations. In the methylenetetrahydrofolate reductase TT group, the greatest reductions of Hcy concentration after folate Study Wrone et al (13) Righetti et al (14) Zoungas et al (12) Jamison et al (20) Mann et al (19) House et al (21) Heinz et al (22) Overall 0·297827 Heterogeneity: t 2 = 0·02; c 2 = 5·50, df = 3 (P = 0·14); l 2 = 45% Test for overall effect: Z = 0·87 (P = 0·39) Heterogeneity: t 2 = 0·04; c 2 = 8·75, df = 5 (P = 0·12); l 2 = 43% Test for overall effect: Z = 0·49 (P = 0·62) Heterogeneity: t 2 = 0·01; c 2 = 7·24, df = 6 (P = 0·30); l 2 = 17% Test for overall effect: Z = 1·86 (P = 0·06) Heterogeneity: t 2 = 0·10; c 2 = 5·63, df = 2 (P = 0·06); l 2 = 64% Test for overall effect: Z = 0·83 (P = 0·41) Heterogeneity: t 2 = 0·00; c 2 = 3·47, df = 4 (P = 0·48); l 2 = 0% Test for overall effect: Z = 1·56 (P = 0·12)…”

Section: Studymentioning

confidence: 99%

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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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B-Vitamin Therapy for Diabetic Nephropathy

Drion¹

2010

JAMA

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Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy

Abstract: isrctn.org Identifier: ISRCTN41332305.

Cited by 269 publications

References 34 publications

The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis

The effect of folate fortification on folic acid-based homocysteine-lowering intervention and stroke risk: a meta-analysis

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

B-Vitamin Therapy for Diabetic Nephropathy

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