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High-Normal Serum Uric Acid Is Associated with Impaired Glomerular Filtration Rate in Nonproteinuric Patients with Type 1 Diabetes

Elizabeth T. Rosolowsky^*,, Linda H. Ficociello^*, Nicholas J. Maselli^*, Monika A. Niewczas^*,, Amanda L. Binns^*, Bijan Roshan^*, James H. Warram^*, and Andrzej S. Krolewski^*,

^* Research Division, Joslin Diabetes Center, Division of Endocrinology at Children's Hospital Boston, and Department of Medicine at Brigham and Women Hospital, Harvard Medical School, Boston, Massachusetts

Correspondence: Dr. Andrzej S. Krolewski, Section on Genetics & Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215. Phone: 617-732-2668; Fax: 617-732-2667; E-mail: Andrzej.Krolewski{at}joslin.harvard.edu

Background and objectives: Early renal function decline begins before the onset of proteinuria in patients with type 1 diabetes. The association of elevated serum uric acid with advanced impaired renal function prompts an examination of its role in early renal function decline in patients before proteinuria develops.

Design, setting, participants, & measurements: Patients with type 1 diabetes and normoalbuminuria or microalbuminuria were recruited to the Second Joslin Kidney Study. A medical history and measurements of BP, hemoglobin A1c, albumin excretion rate, and serum concentrations of uric acid and cystatin C were obtained. Estimated glomerular filtration rate was measured by a cystatin C–based formula.

Results: We studied 364 patients with normoalbuminuria and 311 patients with microalbuminuria. Mean glomerular filtration rate in these groups was 119 and 99 ml/min, respectively. Mildly or moderately impaired renal function (<90 ml/min) was present in 10% of those with normoalbuminuria and 36% of those with microalbuminuria. In univariate and multivariate analyses, lower glomerular filtration rate was strongly and independently associated with higher serum uric acid and higher urinary albumin excretion rate, older age, and antihypertensive treatment.

Conclusions: Serum uric acid concentration in the high-normal range is associated with impaired renal function in patients with type 1 diabetes. Follow-up studies are needed to confirm that this level of serum uric acid is a risk factor for early renal function decline in type 1 diabetes and to determine whether its reduction would prevent the decline.

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