Elevated uric acid increases the risk for kidney disease

Abstract

Recent epidemiologic studies suggest that uric acid predicts the development of new-onset kidney disease, but it is unclear whether uric acid is an independent risk factor. In this study, data from 21,475 healthy volunteers who were followed prospectively for a median of 7 yr were analyzed to examine the association between uric acid level and incident kidney disease (estimated GFR [eGFR] <60 ml/min per 1.73 m(2)). After adjustment for baseline eGFR, a slightly elevated uric acid level (7.0 to 8.9 mg/dl) was associated with a nearly doubled risk for incident kidney disease (odds ratio 1.74; 95% confidence interval 1.45 to 2.09), and an elevated uric acid (> or =9.0 mg/dl) was associated with a tripled risk (odds ratio 3.12; 95% confidence interval 2.29 to 4.25). These increases in risk remained significant even after adjustment for baseline eGFR, gender, age, antihypertensive drugs, and components of the metabolic syndrome (waist circumference, HDL cholesterol, blood glucose, triglycerides, and BP). In a fully adjusted spline model, the risk for incident kidney disease increased roughly linearly with uric acid level to a level of approximately 6 to 7 mg/dl in women and 7 to 8 mg/dl in men; above these levels, the associated risk increased rapidly. In conclusion, elevated levels of uric acid independently increase the risk for new-onset kidney disease.

Figure 1.

Stepwise adjusted OR for development of a GFR < 60 ml/min per 1.73 m² depending on UA group. OR (points) with 95% CI (bars) were calculated by logistic mixed-effect models with increasing adjustment from model M1 to model M6. Reference group was UA <7.0 mg/dl. The SEUAG was defined as 7.0 to 8.9 mg/dl and the EUAG as UA >9.0 mg/dl. M1, unadjusted; M2, adjusted for GFR at baseline; M3, additionally adjusted for age and gender (sum-to-zero-constraints); M4, additionally adjusted for the MF (waist circumference, fasting glucose [natural cubic spline], HDL [log-transformed], triglycerides [log-transformed]); M5, additionally adjusted for MAP (natural cubic spline); and M6, additionally adjusted for antihypertensive drug use.

Figure 2.

OR for development of a GFR <60 ml/min per 1.73 m² depending on UA levels (natural cubic splines) compared with mean UA levels (4.2 mg/dl for women and 5.9 mg/dl for men); stratified for gender and hypertension groups adjusted for GFRb, age, waist circumference, fasting glucose (natural cubic spline), HDL (log-transformed), triglycerides (log-transformed), and antihypertensive drug use. Dashed lines denote 95% CI. Hypertension groups: normal BP, systolic <120 mmHg and diastolic <80 mmHg; prehypertension, systolic 120 to 139 mmHg or diastolic 80 to 89 mmHg; hypertension, systolic ≥140 mmHg or diastolic ≥90 mmHg.