Positive association between plasma homocysteine level and chronic kidney disease.

BACKGROUND Increasing experimental evidence, including recently developed animal models, supports a role for homocysteine in the development of chronic kidney disease (CKD). However, relatively few clinical/epidemiological studies have examined this hypothesis in humans. We examined the relationship between plasma homocysteine level and CKD in a population-based study of older Australians. METHODS Community-based study (1992-1994) among 2,609 individuals (58.6% women), aged 49-98 years, free of clinical cardiovascular disease in the Blue Mountains region, west of Sydney, Australia. The main outcome-of-interest was CKD (n = 461), defined as estimated glomerular filtration rate of <60 ml/min/1.73 m(2). RESULTS Higher plasma homocysteine levels were positively associated with CKD, independent of smoking, body mass index, diabetes mellitus, hypertension, cholesterol levels, and other confounders. The multivariable odds ratio (OR; 95% confidence intervals, CI) comparing quartile 4 of plasma homocysteine (>14 micromol/l) to quartile 1 (< or =9 micromol/l) was 10.44 (6.99-15.60), p-trend <0.0001. This association persisted in both men and women separately. The results were also consistent in subgroup analyses by categories of diabetes mellitus and hypertension. CONCLUSIONS Higher plasma homocysteine levels are associated with CKD in a community-based sample of older Australians. This association appeared to be independent of diabetes mellitus and hypertension.