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

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 of in the development of diabetic nephropathy is not known.

Research Design and Methods: Prospective observational follow-up study 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 three years after onset of diabetes before any patient developed microalbuminuria.

Results: During a median follow-up of 18.1 years (range 1.0-21.8 years), 23 of 263 patients developed persistent macroalbuminuria (urinary albumin excretion rate >300 mg/24h in at least two out of three consecutive samples). In patients with uric acid levels in the highest quartile (above 249 μmol/l), the cumulative incidence of persistent macroalbumnuria was 22.3 % (95% CI: 10.3-34.3) as compared with 9.5 % (95% CI: 3.8-15.2) in patients with uric acid in the three lower quartiles (log rank test, p=0.006). In a Cox proportional hazard 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 early after onset of type 1 diabetes is independently associated with the risk for later development of diabetic nephropathy.