Hyperhomocysteinemia and the development of chronic kidney disease in a general population: The Hisayama study

Background: Hyperhomocysteinemia has been linked with various atherosclerotic diseases, but has not been evaluated sufficiently as a risk factor for the development of chronic kidney disease (CKD) in the general population. Methods: To clarify this issue, we followed up 1,477 community-dwelling individuals without CKD, aged 40 years or older, for 5 years and examined the effects of baseline serum total homocysteine (tHcy) levels on the development of CKD. Results: During follow-up, 88 subjects experienced CKD. Baseline tHcy levels were greater in men than women (1.35 versus 1.04 mg/L [10.0 versus 7.7 μmol/L]; P < 0.01). Age-adjusted 5-year incidences were 2.2% in the low tertile, 5.4% in the middle tertile, and 8.6% in the high tertile of tHcy levels for men and 3.3%, 6.0%, and 6.9% for women, respectively. The difference between the low and high tertiles was statistically significant for both sexes (P < 0.05). In multivariate analysis, these relationships remained substantially unchanged, even after adjustment for other confounding factors, such as systolic blood pressure, antihypertensive medication, hemoglobin A _1c level, total cholesterol level, high-density lipoprotein cholesterol level, habitual smoker status, regular alcohol intake, proteinuria, and baseline kidney function (odds ratio [OR] in the high tertile of tHcy levels, 2.09; 95% confidence interval [CI], 0.66 to 6.61 for men; OR, 2.86; 95% CI, 1.10 to 7.43 for women). Furthermore, baseline tHcy level showed a significantly inverse association with rate of change in kidney function during the 5 years after being adjusted for confounding factors, including baseline kidney function. Conclusion: Our findings suggest that elevated serum tHcy levels are a significant risk factor for the development of CKD in the general population.