JOURNAL ARTICLE

Hyperuricemia and Progression of CKD in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort Study

Kyle E Rodenbach, Michael F Schneider, Susan L Furth, Marva M Moxey-Mims, Mark M Mitsnefes, Donald J Weaver, Bradley A Warady, George J Schwartz
American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation 2015, 66 (6): 984-92
26209544

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 CKiD (CKD in Children) Study.

PREDICTOR: Serum uric acid level (<5.5, 5.5-7.5, and >7.5mg/dL).

OUTCOMES: Composite end point of either >30% decline in glomerular filtration rate (GFR) or initiation of renal replacement therapy.

MEASUREMENTS: Age, sex, race, blood pressure status, GFR, CKD cause, urine protein-creatinine ratio (<0.5, 0.5-<2.0, and ≥2.0mg/mg), age- and sex-specific body mass index > 95th percentile, use of diuretics, and serum uric acid level.

RESULTS: Older age, male sex, lower GFR, and body mass index > 95th percentile were associated with higher uric acid levels. 162, 294, and 171 participants had initial uric acid levels < 5.5, 5.5 to 7.5, or >7.5 mg/dL, respectively. We observed 225 instances of the composite end point over 5 years. In a multivariable parametric time-to-event analysis, compared with participants with initial uric acid levels < 5.5mg/dL, those with uric acid levels of 5.5 to 7.5 or >7.5mg/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 cause, and elevated urine protein-creatinine ratio were also associated with faster times to the composite end point.

LIMITATIONS: The study lacked sufficient data to examine how use of specific medications might influence serum uric acid levels 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.

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