High-Normal Serum Uric Acid Increases Risk of Early Progressive Renal Function Loss in Type 1 Diabetes Results of a 6-year follow-up

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 scrum 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 >= 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% Cl 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 tine 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.