Elsevier

Kidney International

Volume 66, Issue 1, July 2004, Pages 303-312
Kidney International

Clinical Nephrology – Epidemiology – Clinical Trials
Association between serum homocysteine and markers of impaired kidney function in adults in the United States

https://doi.org/10.1111/j.1523-1755.2004.00732.xGet rights and content
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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 m2) 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 B12, and dietary vitamin B6 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 m2) compared to those with normal GFRest levels. Association measures for marginal GFRest levels (60 to 90 mL/min/1.73 m2) 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.

Conclusion

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.

Keywords

chronic kidney disease (CKD)
cardiovascular disease
folate
B vitamins
NHANES

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