Linda H. Ficociello , DSC 1 , 2 , Elizabeth T. Rosolowsky , MD, MPH 1 , 3 , 4 , Monika A. Niewczas , MD, PHD 1 , 4 , Nicholas J. Maselli , BA 1 , Janice M. Weinberg , SCD 2 , Ann Aschengrau , SCD 2 , John H. Eckfeldt , MD, PHD 5 , Robert C. Stanton , MD 1 , 4 , Andrzej T. Galecki , MD, PHD 6 , Alessandro Doria , MD, PHD, MPH 1 , 4 , James H. Warram , MD, SCD 1 , Andrzej S. Krolewski , MD, PHD 1 , 4
23 March 2010
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.
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).
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% 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.