High-Normal Serum Uric Acid Increases Risk of Early Progressive Renal Function Loss in Type 1 Diabetes

OBJECTIVE We previously described a cross-sectional association between serum uric acid and reduced glomerular filtration rate (GFR) in nonproteinuric patients with type 1 diabetes. Here, we prospectively investigated whether baseline uric acid impacts the risk of early progressive renal function loss (early GFR loss) in these patients. RESEARCH DESIGN AND METHODS Patients with elevated urinary albumin excretion (n = 355) were followed for 4-6 years for changes in urinary albumin excretion and GFR. The changes were estimated by multiple determinations of albumin-to-creatinine ratios (ACRs) and serum cystatin C (GFRcystatin). RESULTS At baseline, the medians (25th-75th percentiles) for uric acid, ACR, and GFRcystatin values were 4.6 mg/dl (3.8-5.4), 26.2 mg/g (15.1-56.0), and 129 ml/min per 1.73 m(2) (111-145), respectively. During the 6-year follow-up, significant association (P < 0.0002) was observed between serum uric acid and development of early GFR loss, defined as GFRcystatin decline exceeding 3.3% per year. In baseline uric acid concentration categories (in mg/dl: <3.0, 3.0-3.9, 4.0-4.9, 5.0-5.9, and >or=6), the risk of early GFR loss increased linearly (9, 13, 20, 29, and 36%, respectively). This linear increase corresponds to odds ratio 1.4 (95% CI 1.1-1.8) per 1 mg/dl increase of uric acid. The progression and regression of urinary albumin excretion were not associated with uric acid. CONCLUSIONS We found a clear dose-response relation between serum uric acid and risk of early GFR loss in patients with type 1 diabetes. Clinical trials are warranted to determine whether uric acid-lowering drugs can halt renal function decline before it becomes clinically significant.