Association between serum homocysteine and markers of impaired kidney function in adults in the United States.
BACKGROUND
Circulating homocysteine, a risk factor for cardiovascular disease (CVD), is often elevated in chronic kidney disease and end-stage renal disease (ESRD) patients. Little is known about the risk of elevated homocysteine associated with less advanced renal insufficiency in the community.


METHODS
Serum homocysteine concentration measures (umol/L) from the National Health and Nutrition Examination Survey (NHANES) 1991-1994 participants who were aged >/=40 years and fasted >/=6 hours (1558 men and 1829 women) were categorized as <9, 9 to 11.9, 12 to 14.9, and >/=15. Renal function levels were determined by Modified Diet in Renal Disease (MDRD) estimated glomerular filtration rate (GFRest) (mL/min/1.73 m(2)) and the urinary albumin-to-creatinine ratio (ACR) (mg/g). Cumulative odds ratios (OR) of exceeding any given homocysteine cut point were computed by gender, using ordinal logistic regression. Each model included GFRest (<60, 60 to 90, >/=90), ACR (<15, 15 to <30, >/=30), age, race/ethnicity, red blood cell folate, serum vitamin B(12), and dietary vitamin B(6) intake as independent variables.


RESULTS
The adjusted ORs for elevated homocysteine risk were 9 to 11 times greater in adults with the lowest GFRest levels (<60 mL/min/1.73 m(2)) compared to those with normal GFRest levels. Association measures for marginal GFRest levels (60 to 90 mL/min/1.73 m(2)) were weaker but significant. Albuminuria (ACR >/=30 mg/g) was a significant, independent renal risk factor for elevated homocysteine in men and women (adjusted OR = 1.78, 95% CI 1.08-2.93, and adjusted OR = 1.83, 95% CI 1.21-2.76, respectively) relative to those with low normal albumin excretion, but high normal albuminuria (ACR = 15-30 mg/g) was not.


CONCLUSIONS
In the general population, renal insufficiency is strongly associated with an increased risk of elevated circulating homocysteine, independent of B vitamin status. These results raise the possibility that elevated homocysteine may be an important risk factor to explain the heavy burden of CVD associated with kidney disease.
Francis
Mildred E
ME
Social & Scientific Systems, Inc., Silver Spring, Maryland, USA.
Eggers
Paul W
PW
Hostetter
Thomas H
TH
Briggs
Josephine P
JP
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009749:Nutrition Surveys; D016017:Odds Ratio; D051437:Renal Insufficiency / Q000097:blood* / Q000503:physiopathology; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D012720:Severity of Illness Index; D014481:United States
D015415:Biomarkers; D012709:Serum Albumin; D006710:Homocysteine