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 m². Results: Higher plasma homocys- teine 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 μmol/l) to quartile 1 (≤9 μmol/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.