Effect of B-vitamin therapy on progression of diabetic nephropathy: a randomized controlled trial.
BACKGROUND
Hyperhomocysteinemia is frequently observed in patients with diabetic nephropathy. B-vitamin therapy (folic acid, vitamin B(6), and vitamin B(12)) 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.


METHODS
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.


METHODS
Single tablet of B vitamins containing folic acid (2.5 mg/d), vitamin B(6) (25 mg/d), and vitamin B(12) (1 mg/d), or matching placebo.


METHODS
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 m(2) in the B-vitamin group compared with 10.7 (1.7) mL/min/1.73 m(2) 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) micromol/L at 36 months in the B-vitamin group compared with a mean (SE) increase of 2.6 (0.4) micromol/L in the placebo group (mean difference, -4.8; 95% CI, -6.1 to -3.7; P < .001, in favor of B vitamins).


CONCLUSIONS
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.


BACKGROUND
isrctn.org Identifier: ISRCTN41332305.
House
Andrew A
AA
Division of Nephrology, University of Western Ontario, London, Ontario, Canada.
Eliasziw
Misha
M
Cattran
Daniel C
DC
Churchill
David N
DN
Oliver
Matthew J
MJ
Fine
Adrian
A
Dresser
George K
GK
Spence
J David
JD
D000368:Aged; D003928:Diabetic Nephropathies / Q000150:complications* / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D005919:Glomerular Filtration Rate; D006801:Humans; D020138:Hyperhomocysteinemia / Q000188:drug therapy* / Q000209:etiology; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000009:adverse effects; D025101:Vitamin B 6 / Q000008:administration & dosage* / Q000009:adverse effects; D014803:Vitamin B Complex / Q000008:administration & dosage* / Q000009:adverse effects
D014803:Vitamin B Complex; D025101:Vitamin B 6; D005492:Folic Acid; D014805:Vitamin B 12