Large study provides more epidemiologic evidence of an association.


STOCKHOLM—Researchers in Vienna have found that higher levels of uric acid are associated with an increased risk of new-onset kidney disease. The new findings add to a growing body of data supporting such an association, including a recently published study by an American team.

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At the 2008 congress of the European Renal Association-European Dialysis and Transplant Association here, Rudolf P. Obermayr, MD, of Donauspital, Sozialmedizinisches Zentrum Ost der Stadt Wien, reported on a study of 21,475 apparently healthy volunteers of the general Viennese population (46.5% women). Patients were enrolled between 1990 and 2007.


After their baseline examination, the participants completed a median of two follow-up examinations. Of the 21,475 individuals, 19,466 had uric acid levels below 7 mg/dL (mean 4.9 mg/dL); 1,821 had a level of 7-9 mg/dL (mean 7.7 mg/dL); and 188 had a level above 9 mg/dL (mean 9.7 mg/dL).


After a median follow-up of seven years, those with a uric acid level of 7-9 mg/dL (slightly elevated) had a 46% increased risk of kidney disease compared with the reference group (subjects with a uric acid level below 7 mg/dL), after adjusting for baseline glomerular filtration rate (GFR), age, gender, components of the metabolic syndrome, and mean arterial BP, Dr. Obermayr said.


The investigators defined kidney disease as an estimated GFR less than 60 mL/min per 1.73 m2. The risk was twofold greater among subjects with a uric acid level above 9.0 mg/dL (elevated). After additional adjustment for alcohol consumption (more than three drinks per week vs. three or fewer drinks per week), the risk was 29% and 1.8 times greater in the slightly elevated and elevated uric acid groups. Finally, after adjusting for antihypertensive drug use, the risk was 26% and 67% higher.


“Elevated uric acid levels obviously increase the risk of new-onset kidney disease,” the authors concluded in their poster.


Although previous studies have shown that elevated uric acid raises the risk of renal disease, the new study adjusted for metabolic factors that previously were not considered, Dr. Obermayr said. For this reason and because of the large number of patients in the study, the new study provides strong epidemiologic evidence linking uric acid to development of renal disease, he said.

The next step is to perform an interventional trial to determine if lowering uric acid levels is associated with a reduced risk of new-onset kidney disease.


The findings of Dr. Obermayr’s group are consistent with those of a team at Tufts Medical Center in Boston, which found that elevated serum uric acid levels are a modest independent risk factor for new-onset kidney disease in the general population. Their finding is based on a study of 13,338 individuals with intact renal function. These individuals were part of two community-based cohorts. At baseline, subjects had a mean uric acid level of 5.9 mg/dL, a mean serum creatinine level of 0.9 mg/dL, and a mean estimated GFR of 90.4 mL/min per 1.73 m2.


During 8.5 years of follow-up, 712 patients (5.6%) had incident kidney disease (defined as a GFR decrease of 15 mL/min per 1.73 m2 with a final GFR less than 60 mL/min per 1.73 m2), and 302 subjects (2.3%) had incident kidney disease defined by a creatinine rise of 0.4 mg/dL or greater with a final serum creatinine level greater than 1.4 mg/dL in men and 1.2 mg/dL in women. Each 1 mg/dL rise in uric acid was associated with a 7% increase in the risk of kidney disease, after adjusting for numerous potential confounders, including age, gender, race, diabetes, systolic BP, hypertension, CVD, left ventricular hypertrophy, smoking, alcohol use, education, lipids, and albumin.


The study, led by Daniel E. Weiner, MD, is described in the Journal of the American Society of Nephrology (online ahead of print).