Relationship between homocysteine and mortality in chronic kidney disease.
BACKGROUND
The relationship between total homocysteine (tHcy) and outcomes has not been investigated in patients with chronic kidney disease stages 3 to 4.


RESULTS
The Modification of Diet in Renal Disease Study was a randomized, controlled trial of 840 patients. Serum tHcy was measured in frozen samples collected at baseline (n=804). Survival status and cause of death were obtained from the National Death Index. To evaluate its association with all-cause and cardiovascular disease (CVD) mortality, tHcy was evaluated both as tertiles (<14.7, 14.7 to 19.5, > or =19.6 micromol/L) and as a continuous variable (per 10/micromol/L). Participants had a mean age of 52+/-12 years and glomerular filtration rate (GFR) of 33+/-12 mL/min per 1.73 m2; 60% were male, and 85% were white. During a median follow-up of 10 years, 195 (24%) died from any cause, and 118 (15%) from CVD. The level of GFR was lower and proteinuria higher in the highest tHcy tertile. There was no association between the highest tertile of tHcy and all-cause (hazard ratio [HR]; 95% confidence interval [CI[, 1.32, 0.94 to 1.85) or CVD (HR; 95% CI, 1.50, 0.96 to 2.34) mortality in univariate analyses; this association was further attenuated by adjustment for GFR (HR; 95% CI all-cause, 1.04, 0.72 to 1.51; CVD, 1.20, 0.73 to 1.95). There was no association between tHcy as a continuous variable and all-cause (0.98, 0.83 to 1.16) or CVD (1.04, 0.85 to 1.27) mortality.


CONCLUSIONS
Hyperhomocystinemia does not appear to be a risk factor for all-cause or CVD mortality in the Modification of Diet in Renal Disease Study. Prior studies demonstrating an association between tHcy and CVD risk may have inadequately adjusted for the confounding effects of kidney function.
Menon
Vandana
V
Division of Nephrology, Department of Medicine, Tufts-New England Medical Center, Boston, MA, USA.
Sarnak
Mark J
MJ
Greene
Tom
T
Wang
Xuelei
X
Pereira
Arema A
AA
Beck
Gerald J
GJ
Kusek
John W
JW
Selhub
Jacob
J
Collins
Allan J
AJ
Levey
Andrew S
AS
Shlipak
Michael G
MG
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000401:mortality*; D002423:Cause of Death; D002908:Chronic Disease; D004044:Dietary Proteins / Q000494:pharmacology*; D005260:Female; D005919:Glomerular Filtration Rate; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007674:Kidney Diseases / Q000453:epidemiology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009026:Mortality
D004044:Dietary Proteins; D006710:Homocysteine