High-normal serum uric acid increases risk of early progressive renal function loss in type 1 diabetes: results of a 6-year follow-up

Abstract

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.

Figure 1

Risks during 4–6 years follow-up of early GFR loss (A), CKD stage 3 (B), progression of ACR (C), or regression of ACR according to baseline concentration of serum uric acid (D). Baseline serum uric acid values (mg/dl) were <3.0 for 23 patients, between 3.0 and 3.9 for 78 patients, between 4.0 and 4.9 for 118 patients, between 5.0 and 5.9 for 96 patients, and ≥6.0 for 53 patients. Median uric acid concentration in the cohort was 4.6 mg/dl. A: Test for trend in risk of early GFR loss with baseline serum uric acid category was significant, P = 0.0002. B: Test for trend in risk of CKD stage 3 with baseline serum uric acid category significant, P = 0.0005. C: Test for trend in risk of progression of ACR with baseline uric acid category was not statistically significant, P = 0.34. D: Test for trend in risk of regression of ACR with baseline uric acid category was not statistically significant, P = 0.65.