Serum homocysteine levels are associated with the development of (micro)albuminuria - The Hoorn Study

Microalbuminuria is a strong indicator of the risk of future cardiovascular disease and renal dysfunction. Slightly increased levels of homocysteine, an independent risk factor for atherothrombotic disease, have recently been found to be associated with the presence of (micro)albuminuria. However, i t is unknown whether increased homocysteine levels precede the occurrence o f (micro)albuminuria. Normoalbuminuric subjects (n=316, 66 with non-insulin -dependent diabetes mellitus [NIDDM]) of an age-stratified, sex-stratified, and glucose tolerance-stratified sample of a population-based cohort study were investigated at baseline and after a mean follow-up duration of 6.1 y ears. Development of (micro)albuminuria was defined as a mean albumin-to-cr eatinine ratio >2.0 mg/mmol at the follow-up examination. The cumulative in cidence of (micro)albuminuria was 14.0% (9.7 % to 18.3%) among nondiabetic subjects and 22.7% (12.9% to 32.5%) among NIDDM patients. Age-adjusted, sex -adjusted, and glucose tolerance status-adjusted logistic regression analys es showed development of (micro)albuminuria to be significantly associated with baseline homocysteine levels >19.0 mu mol/L compared with homocysteine levels <9.1 <mu>mo/L (odds ratio [OR] 5.1, 95% CI 1.1 to 23.0). For homocy steine levels of 4.1 to 14.0 mu mol/L, and 14.1 to 19.0 mu mol/L, the value s were OR 1.2 (95% CI 0.5 to 3.0) and OR 1.8 (95% CI 0.6 to 5.3), respectiv ely. Additional adjustment for baseline insulin resistance, blood pressure, body mass index, presence of cardiovascular disease and retinopathy, curre nt smoking, or estimates of glomerular filtration rate did not materially a ffect the results. Substituting homocysteine levels as a continuous variabl e for categories of homocysteine levels showed that a 5-mu mol/L increase o f the homocysteine level was associated with an increased risk of developin g (micro)albuminuria (OR 1.38, 95% CI 0.97 to 1.95). Analyses performed in nondiabetic and diabetic subjects separately gave similar results among non diabetic subjects. Among diabetic subjects, the association between homocys teine level and (micro)albuminuria could not be estimated, because there wa s an insufficient number of diabetic subjects with high homocysteine levels . Hyperhomocysteinemia is an independent determinant of the development of (micro)albuminuria among nondiabetic subjects, even after adjustment for es timates of glomerular filtration rate. We could neither confirm nor reject an association between homocysteine levels and the development of (micro)al buminuria among NIDDM subjects. These data suggest that homocysteine may pl ay a pathophysiological role in the development of (micro)albuminuria.