Serum Uric Acid as a Predictor for Development of Diabetic Nephropathy in Type 1 Diabetes
An Inception Cohort Study
- 1Steno Diabetes Center, Gentofte, Denmark;
- 2Department of Clinical Physiology and Nuclear Medicine, Glostrup Hospital, Glostrup, Denmark;
- 3the Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado;
- 4Department of Medical Endocrinology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark;
- 5Faculty of Health Science, University of Aarhus, Denmark.
- Corresponding author: Peter Hovind, phovind{at}dadlnet.dk.
Abstract
OBJECTIVE Experimental and clinical studies have suggested that uric acid may contribute to the development of hypertension and kidney disease. Whether uric acid has a causal role in the development of diabetic nephropathy is not known. The objective of the present study is to evaluate uric acid as a predictor of persistent micro- and macroalbuminuria.
RESEARCH DESIGN AND METHODS This prospective observational follow-up study consisted of an inception cohort of 277 patients followed from onset of type 1 diabetes. Of these, 270 patients had blood samples taken at baseline. In seven cases, uric acid could not be determined; therefore, 263 patients (156 men) were available for analysis. Uric acid was measured 3 years after onset of diabetes and before any patient developed microalbuminuria.
RESULTS During a median follow-up of 18.1 years (range 1.0–21.8), 23 of 263 patients developed persistent macroalbuminuria (urinary albumin excretion rate >300 mg/24 h in at least two of three consecutive samples). In patients with uric acid levels in the highest quartile (>249 μmol/l), the cumulative incidence of persistent macroalbumnuria was 22.3% (95% CI 10.3–34.3) compared with 9.5% (3.8–15.2) in patients with uric acid in the three lower quartiles (log-rank test, P = 0.006). In a Cox proportional hazards model with sex and age as fixed covariates, uric acid was associated with subsequent development of persistent macroalbuminuria (hazard ratio 2.37 [95% CI 1.04–5.37] per 100 μmol/l increase in uric acid level; P = 0.04). Adjustment for confounders did not change the estimate significantly.
CONCLUSIONS Uric acid level soon after onset of type 1 diabetes is independently associated with risk for later development of diabetic nephropathy.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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The funding sources had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
- Received January 6, 2009.
- Accepted April 6, 2009.
- © 2009 by the American Diabetes Association.
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