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Am J Kidney Dis. 2015 Dec;66(6):984-92. doi: 10.1053/j.ajkd.2015.06.015. Epub 2015 Jul 21.

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

Author information

1
University of Rochester Medical Center, Rochester, NY.
2
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
3
Children's Hospital of Philadelphia, Philadelphia, PA.
4
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.
5
Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
6
Levine Children's Hospital, Charlotte, NC.
7
Children's Mercy Hospital, Kansas City, MO.
8
University of Rochester Medical Center, Rochester, NY. Electronic address: george_schwartz@urmc.rochester.edu.

Abstract

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.

KEYWORDS:

CKD progression; CKiD (Chronic Kidney Disease in Children); Uric acid; adolescents; children; chronic kidney disease (CKD); disease trajectory; end-stage renal disease (ESRD); glomerular filtration rate (GFR); hyperuricemia; pediatric kidney disease; renal function decline; renal replacement therapy (RRT); risk factor; urate

PMID:
26209544
PMCID:
PMC4658318
DOI:
10.1053/j.ajkd.2015.06.015
[Indexed for MEDLINE]
Free PMC Article

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