Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study

TY - JOUR

T1 - Serum uric acid as a predictor for development of diabetic nephropathy in type 1 diabetes: an inception cohort study

AU - Hovind, Peter

AU - Rossing, Peter

AU - Tarnow, Lise

AU - Johnson, Richard J

AU - Parving, Hans-Henrik

N1 - Keywords: Adolescent; Adult; Albuminuria; Blood Pressure; Cohort Studies; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Follow-Up Studies; Humans; Incidence; Male; Predictive Value of Tests; Prospective Studies; Risk Factors; Time Factors; Uric Acid; Young Adult

PY - 2009

Y1 - 2009

N2 - 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 micromol/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 micromol/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.

AB - 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 micromol/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 micromol/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.

U2 - 10.2337/db09-0014

DO - 10.2337/db09-0014

M3 - Journal article

C2 - 19411615

SN - 0012-1797

VL - 58

SP - 1668

EP - 1671

JO - Diabetes

JF - Diabetes

IS - 7

ER -