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Randomised controlled trial
In diabetic nephropathy, high doses of vitamin B decrease glomerular filtration rate and increase risk of the composite outcome of a vascular event or all-cause mortality compared with placebo
  1. Vivek Bhalla
  1. Division of Nephrology/Department of Medicine, Stanford University School of Medicine, Palo Alto, California, USA
  1. Correspondence to Vivek Bhalla
    Division of Nephrology, Department of Medicine, Stanford University School of Medicine, 780 Welch Road, Suite 106, Palo Alto, CA 94304, USA; vbhalla{at}

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Hyperhomocysteinemia increases oxidative stress, a common pathogenic mechanism of injury in chronic kidney disease (CKD) and atherosclerosis.1 Plasma homocysteine has been linked to worsening diabetic nephropathy,2 but no therapeutic trials have assessed the effect of vitamin-based, homocysteine-lowering therapy on slowing the progression of disease. Moreover, hyperhomocysteinemia has been associated with an increased incidence of cardiovascular (CV) disease,3 and participants with impaired kidney function have elevated plasma homocysteine. House and colleagues sought to determine whether B-vitamin therapy reduces progression of CKD and incidence of CV events in participants with diabetic nephropathy.


The DIVINe (Diabetic Intervention with Vitamins to Improve Nephropathy) trial was a multicentre, randomised, double blind study consisting of oral B-vitamin therapy (2.5 mg/day folic acid, 25 mg/day vitamin B6 and 1 mg/day vitamin B12) versus placebo to determine the effect of treatment on the rate of decline of glomerular filtration rate (GFR) over a 36-month period. Two hundred thirty-eight …

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  • Competing interests None.