Background
Hyperuricemia is associated with essential hypertension in children. No previous studies have evaluated the effect of hyperuricemia on progression of chronic kidney disease (CKD) in children.
Study Design
Prospective observational cohort study.
Setting & Participants
Children and adolescents (n=678 cross-sectional; n=627 longitudinal) with a median age of 12.3 (IQR, 8.6–15.6) years enrolled at 52 North American sites of the CKD in Children (CKiD) study.
Predictor
Serum uric acid (<5.5, 5.5–7.5, and >7.5 mg/dL).
Outcomes
Composite endpoint of either >30% decline in glomerular filtration rate (GFR) or initiation of renal replacement therapy.
Measurements
Age, sex, race, blood pressure status, GFR, CKD etiology, urine proteincreatinine ratio (<0.5, 0.5 to <2.0, ≥2.0 mg/mg), age- and sex-specific BMI >95th percentile, use of diuretics, and serum uric acid.
Results
162, 294, and 171 participants had initial uric acid < 5.5, 5.5–7.5, or > 7.5 mg/dL, respectively. Older age, male sex, lower GFR, and BMI > 95th percentile were associated with higher uric acid. We observed 225 instances of the composite endpoint over five years. In a multivariable parametric time-to-event analysis, compared to participants with initial uric acid <5.5 mg/dL, those with uric acid of 5.5–7.5 or >7.5 mg/dL had 17% shorter (relative time, 0.83; 95% CI, 0.62–1.11) or 38% shorter (relative time, 0.62; 95% CI, 0.45–0.85) times to event, respectively. Hypertension, lower GFR, glomerular CKD etiology, and elevated urine protein-creatinine ratio were also associated with faster times to the composite endpoint.
Limitations
The study lacked sufficient data to examine how use of specific medications might influence serum uric acid and CKD progression.
Conclusions
Hyperuricemia is a previously undescribed, independent risk factor for faster progression of CKD in children and adolescents. It is possible that treatment of children and adolescents with CKD with urate-lowering therapy could slow disease progression.