High-Normal Serum Uric Acid Increases Risk of Early Declining Renal Function In Type 1 Diabetes: Results of 6-year Follow-up.

  1. Andrzej S. Krolewski, MD, PhD (Andrzej.krolewski{at}joslin.harvard.edu)1,4
  1. From the 1 Research Division, Joslin Diabetes Center, Boston, Massachusetts
  2. 2School of Public Health, Boston University, Boston, Massachusetts
  3. 3Division of Endocrinology at Children's Hospital, Boston, Massachusetts
  4. 4Harvard Medical School, Boston, Massachusetts
  5. 5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN
  6. 6University of Michigan Medical School, Ann Arbor, MI

Abstract

Objective: We previously described cross-sectional association between serum uric acid (UA) and reduced glomerular filtration rate (GFR) in non-proteinuric patients with type 1 diabetes. Here we prospectively investigated whether baseline UA impacts the risk of early Declining Renal Function (early DRF) 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 (ACR) and serum cystatin C (GFRcystatin).

Results: At baseline the medians (25th, 75th percentiles) for UA, 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/1.73 m2 (111,145), respectively. During the 6 year follow-up, significant association (p<0.0002) was observed between serum UA and development of early DRF, defined as GFRcystatin decline exceeding 3.3% per year. In baseline UA concentration categories (mg/dL) <3.0, 3.0-3.9, 4.0-4.9, 5.0-5.9, and 6+, the risk of early DRF increased linearly: 9, 13, 20, 29, and 36%, respectively. This linear increase corresponds to an OR=1.4 (95% CI: 1.1, 1.8) per 1 mg/dL increase of UA. The progression and regression of urinary albumin excretion were not associated with UA.

Conclusions: We found a clear dose-response relation between serum UA and risk of early DRF in patients with Type 1 diabetes. Clinical trials are warranted to determine whether UA lowering drugs can halt renal function decline before it becomes clinically significant.

Footnotes

    • Received February 4, 2010.
    • Accepted March 10, 2010.

This Article

  1. Diabetes Care
  1. All Versions of this Article:
    1. dc10-0227v1
    2. 33/6/1337 most recent