Effect of B-Vitamin Therapy on Progression of Diabetic Nephropathy
A Randomized Controlled Trial
- Andrew A. House, MD;
- Misha Eliasziw, PhD;
- Daniel C. Cattran, MD;
- David N. Churchill, MD;
- Matthew J. Oliver, MD;
- Adrian Fine, MD;
- George K. Dresser, MD;
- J. David Spence, MD
- Author Affiliations: Division of Nephrology (Dr House), Division of Clinical Pharmacology (Drs Dresser and Spence), and Robarts Research Institute (Dr Spence), University of Western Ontario, London, Ontario; Department of Community Health Sciences, Clinical Neurosciences, and Oncology, University of Calgary, Calgary, Alberta (Dr Eliasziw); Division of Nephrology, University of Toronto, Toronto, Ontario (Drs Cattran and Oliver); Division of Nephrology, McMaster University, Hamilton, Ontario (Dr Churchill); and Division of Nephrology, University of Manitoba, Winnipeg, Manitoba (Dr Fine), Canada.
Abstract
Context Hyperhomocysteinemia is frequently observed in patients with diabetic nephropathy. B-vitamin therapy (folic acid, vitamin B6, and vitamin B12) has been shown to lower the plasma concentration of homocysteine.
Objective To determine whether B-vitamin therapy can slow progression of diabetic nephropathy and prevent vascular complications.
Design, Setting, and Participants A multicenter, randomized, double-blind, placebo-controlled trial (Diabetic Intervention with Vitamins to Improve Nephropathy [DIVINe]) at 5 university medical centers in Canada conducted between May 2001 and July 2007 of 238 participants who had type 1 or 2 diabetes and a clinical diagnosis of diabetic nephropathy.
Intervention Single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B6 (25 mg/d), and vitamin B12 (1 mg/d), or matching placebo.
Main Outcome Measures Change in radionuclide glomerular filtration rate (GFR) between baseline and 36 months. Secondary outcomes were dialysis and a composite of myocardial infarction, stroke, revascularization, and all-cause mortality. Plasma total homocysteine was also measured.
Results The mean (SD) follow-up during the trial was 31.9 (14.4) months. At 36 months, radionuclide GFR decreased by a mean (SE) of 16.5 (1.7) mL/min/1.73 m2 in the B-vitamin group compared with 10.7 (1.7) mL/min/1.73 m2 in the placebo group (mean difference, −5.8; 95% confidence interval [CI], −10.6 to −1.1; P = .02). There was no difference in requirement of dialysis (hazard ratio [HR], 1.1; 95% CI, 0.4-2.6; P = .88). The composite outcome occurred more often in the B-vitamin group (HR, 2.0; 95% CI, 1.0-4.0; P = .04). Plasma total homocysteine decreased by a mean (SE) of 2.2 (0.4) μmol/L at 36 months in the B-vitamin group compared with a mean (SE) increase of 2.6 (0.4) μmol/L in the placebo group (mean difference, −4.8; 95% CI, −6.1 to −3.7; P < .001, in favor of B vitamins).
Conclusion Among patients with diabetic nephropathy, high doses of B vitamins compared with placebo resulted in a greater decrease in GFR and an increase in vascular events.
Trial Registration isrctn.org Identifier: ISRCTN41332305
