High-Normal Serum Uric Acid Increases Risk of Early Declining Renal Function In Type 1 Diabetes: Results of 6-year Follow-up.
- Linda H Ficociello, DSc1,2,
- Elizabeth T Rosolowsky, MD, MPH1,3,4,
- Monika A Niewczas, MD, PhD1,4,
- Nicholas J Maselli, BA1,
- Janice M Weinberg, ScD2,
- Ann Aschengrau, ScD2,
- John H Eckfeldt, MD, PhD5,
- Robert C Stanton, MD1,4,
- Andrzej T Galecki, MD, PhD6,
- Alessandro Doria, MD, PhD, MPH1,4,
- James H Warram, MD, ScD1 and
- Andrzej S. Krolewski, MD, PhD (Andrzej.krolewski{at}joslin.harvard.edu)1,4
- From the 1 Research Division, Joslin Diabetes Center, Boston, Massachusetts
- 2School of Public Health, Boston University, Boston, Massachusetts
- 3Division of Endocrinology at Children's Hospital, Boston, Massachusetts
- 4Harvard Medical School, Boston, Massachusetts
- 5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN
- 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
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- Received February 4, 2010.
- Accepted March 10, 2010.
- Copyright © American Diabetes Association
