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

doi:10.1053/j.ajkd.2015.06.015

American Journal of Kidney Diseases

Volume 66, Issue 6, December 2015, Pages 984-992

https://doi.org/10.1053/j.ajkd.2015.06.015 Get rights and content

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 >7.5 mg/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 ≥2.0 mg/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 < 5.5 mg/dL, those with uric acid levels of 5.5 to 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 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.

Section snippets

Participants

The CKiD (CKD in Children) Study comprises a cohort of 891 children seen at a total of 55 pediatric nephrology centers across North America. The study design and conduct were approved by an observational study monitoring board appointed by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and by the institutional review boards of each participating center. Briefly, participants had a median age of 11.1 (interquartile range [IQR], 7.7-14.8) years, 62% were male, and

Descriptive Statistics

Median index visit uric acid level was 6.5 (IQR, 5.4-7.6) mg/dL (Fig 1). Descriptive statistics for the 678 individuals included in the cross-sectional analysis appear in Table 1. Median GFR was 58.1 mL/min/1.73 m², 32% of CKiD participants had a glomerular CKD diagnosis, 27% had UPCR of 0.5 to <2.0 mg/mg, and 13% had UPCR ≥ 2.0 mg/mg. Overweight participants (age- and sex-specific BMI > 95th percentile) constituted 18% of the study population. Forty-four were taking diuretics.

Cross-sectional Analyses

In univariable regression

Discussion

Age, male sex, initial GFR, and age-and sex-specific BMI > 95th percentile were positively associated with elevated serum uric acid levels in the multivariable cross-sectional analysis. Race, systolic or diastolic BP > 95th percentile or systolic or diastolic BP ≤ 95th percentile with antihypertensive medications, CKD cause (glomerular vs nonglomerular), and diuretic use were not associated with significantly higher uric acid levels. Considering the positive data for this association in adults and

Acknowledgements

Data in this study were collected by the CKiD prospective cohort study (www.statepi.jhsph.edu/ckid) with clinical coordinating centers at Children’s Mercy Hospital and the University of Missouri–Kansas City (Principal Investigator [PI], Bradley Warady, MD) and The Children’s Hospital of Philadelphia (PI, Susan Furth, MD, PhD), data coordinating center at the Johns Hopkins Bloomberg School of Public Health (PI, Alvaro Muñoz, PhD), and the Central Biochemistry Laboratory at the University of

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Original InvestigationPathogenesis and Treatment of Kidney DiseaseHyperuricemia and Progression of CKD in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort Study

Background

Study Design

Setting & Participants

Predictor

Outcomes

Measurements

Results

Limitations

Conclusions

Section snippets

Participants

Descriptive Statistics

Cross-sectional Analyses

Discussion

Acknowledgements

Am J Kidney Dis

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

J Pediatr

Mayo Clin Proc

Am J Kidney Dis

Clin Biochem

Clin Chim Acta

Am J Kidney Dis

Am J Kidney Dis

Serum uric acid and the risk of hypertension and chronic kidney disease

Curr Opin Rheumatol

Serum uric acid level, longitudinal blood pressure, renal function, and long-term mortality in treated hypertensive patients

Hypertension

Serum urate and incidence of kidney disease among veterans with gout

J Rheumatol

Increased uric acid promotes decline of the renal function in hypertensive patients: a 10-year observational study

Intern Med

Childhood uric acid predicts adult blood pressure: the Bogalusa Heart Study

Hypertension

Uric acid level and elevated blood pressure in US adolescents: National Health and Nutrition Examination Survey, 1999-2006

Hypertension

Relation between serum uric acid and blood pressure in adolescents

Ann Hum Biol

Serum uric acid and ambulatory blood pressure in children with primary hypertension

Pediatr Res

Serum uric acid levels are associated with high blood pressure in Chinese children and adolescents aged 10-15 years

J Hypertens

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