This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jager, A. Articles by Stehouwer, C. D. A. Search for Related Content PubMed PubMed Citation Articles by Jager, A. Articles by Stehouwer, C. D. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:74.)
© 2001 American Heart Association, Inc.

Vascular Biology

Serum Homocysteine Levels Are Associated With the Development of (Micro)albuminuria

The Hoorn Study

Agnes Jager; Piet J. Kostense; Giel Nijpels; Jacqueline M. Dekker; Robert J. Heine; Lex M. Bouter; Ab J. M. Donker; Coen D. A. Stehouwer

From the Institute for Research in Extramural Medicine (A.J., P.J.K., G.N., J.M.D., R.J.H., L.M.B., C.D.A.S.), Vrije Universiteit; the Department of Clinical Epidemiology and Biostatistics (P.J.K.), Vrije Universiteit; the Department of Internal Medicine (R.J.H., A.J.M.D., C.D.A.S.), Academic Hospital Vrije Universiteit; and the Institute for Cardiovascular Research (A.J.M.D., C.D.A.S.), Vrije Universiteit, Amsterdam, the Netherlands.

Correspondence to Dr Coen D.A. Stehouwer, Department of Internal Medicine, University Hospital Vrije Universiteit, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands. E-mail cda.stehouwer{at}azvu.nl

Abstract—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, it is unknown whether increased homocysteine levels precede the occurrence of (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 years. Development of (micro)albuminuria was defined as a mean albumin-to-creatinine ratio >2.0 mg/mmol at the follow-up examination. The cumulative incidence 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 analyses showed development of (micro)albuminuria to be significantly associated with baseline homocysteine levels >19.0 µmol/L compared with homocysteine levels <9.1 µmol/L (odds ratio [OR] 5.1, 95% CI 1.1 to 23.0). For homocysteine levels of 9.1 to 14.0 µmol/L and 14.1 to 19.0 µmol/L, the values were OR 1.2 (95% CI 0.5 to 3.0) and OR 1.8 (95% CI 0.6 to 5.3), respectively. Additional adjustment for baseline insulin resistance, blood pressure, body mass index, presence of cardiovascular disease and retinopathy, current smoking, or estimates of glomerular filtration rate did not materially affect the results. Substituting homocysteine levels as a continuous variable for categories of homocysteine levels showed that a 5-µmol/L increase of the homocysteine level was associated with an increased risk of developing (micro)albuminuria (OR 1.38, 95% CI 0.97 to 1.95) . Analyses performed in nondiabetic and diabetic subjects separately gave similar results among nondiabetic subjects. Among diabetic subjects, the association between homocysteine level and (micro)albuminuria could not be estimated, because there was 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 estimates of glomerular filtration rate. We could neither confirm nor reject an association between homocysteine levels and the development of (micro)albuminuria among NIDDM subjects. These data suggest that homocysteine may play a pathophysiological role in the development of (micro)albuminuria.

Key Words: homocysteine • microalbuminuria • prospective studies • non–insulin-dependent diabetes mellitus

This article has been cited by other articles:

				V. Menon, M. J. Sarnak, T. Greene, X. Wang, A. A. Pereira, G. J. Beck, J. W. Kusek, J. Selhub, A. J. Collins, A. S. Levey, et al. Relationship Between Homocysteine and Mortality in Chronic Kidney Disease Circulation, March 28, 2006; 113(12): 1572 - 1577. [Abstract] [Full Text] [PDF]

				P. Tessari, A. Coracina, E. Kiwanuka, M. Vedovato, M. Vettore, A. Valerio, M. Zaramella, and G. Garibotto Effects of Insulin on Methionine and Homocysteine Kinetics in Type 2 Diabetes With Nephropathy Diabetes, October 1, 2005; 54(10): 2968 - 2976. [Abstract] [Full Text] [PDF]

				E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw Biochemical risk markers: a novel area for better prediction of renal risk? Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508. [Full Text] [PDF]

				V. Fonseca, C. Desouza, S. Asnani, and I. Jialal Nontraditional Risk Factors for Cardiovascular Disease in Diabetes Endocr. Rev., February 1, 2004; 25(1): 153 - 175. [Abstract] [Full Text] [PDF]

				B. Ozmen, D. Ozmen, N. Turgan, S. Habif, I. Mutaf, and O. Bayindir Association Between Homocysteinemia and Renal Function in Patients with Type 2 Diabetes Mellitus Ann. Clin. Lab. Sci., July 1, 2002; 32(3): 279 - 286. [Abstract] [Full Text] [PDF]

				J. B. Meigs, P. F. Jacques, J. Selhub, D. E. Singer, D. M. Nathan, N. Rifai, R. B. D'Agostino Sr., and P. W.F. Wilson Fasting Plasma Homocysteine Levels in the Insulin Resistance Syndrome: The Framingham Offspring Study Diabetes Care, August 1, 2001; 24(8): 1403 - 1410. [Abstract] [Full Text] [PDF]