TY - JOUR
T1 - Hyperuricemia and progression of CKD in children and adolescents
T2 - The Chronic Kidney Disease in Children (CKiD) cohort study
AU - Rodenbach, Kyle E.
AU - Schneider, Michael F.
AU - Furth, Susan L.
AU - Moxey-Mims, Marva M.
AU - Mitsnefes, Mark M.
AU - Weaver, Donald J.
AU - Warady, Bradley A.
AU - Schwartz, George J.
N1 - Funding Information:
Support: The CKiD Study is funded by the NIDDK , with additional funding from the National Institute of Neurological Disorders and Stroke , the Eunice Kennedy Shriver National Institute of Child Health and Human Development , and the National Heart, Lung and Blood Institute ( U01 DK82194 , U01-DK-66143 , U01-DK-66174 , and U01-DK-66116 ). The NIDDK had a role in the study design. Mr Rodenbach was also supported by the Strong Children’s Research Center of the University of Rochester Department of Pediatrics for a summer fellowship in 2013, during which time he began work on the uric acid project. GE Healthcare provided the Omnipaque 300 T for the iohexol GFR studies, and Paula Maier performed data entry.
Publisher Copyright:
© 2015 National Kidney Foundation, Inc.
PY - 2015/12
Y1 - 2015/12
N2 - 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.
AB - 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.
KW - CKD progression
KW - CKiD (Chronic Kidney Disease in Children)
KW - Uric acid
KW - adolescents
KW - children
KW - chronic kidney disease (CKD)
KW - disease trajectory
KW - end-stage renal disease (ESRD)
KW - glomerular filtration rate (GFR)
KW - hyperuricemia
KW - pediatric kidney disease
KW - renal function decline
KW - renal replacement therapy (RRT)
KW - risk factor
KW - urate
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U2 - 10.1053/j.ajkd.2015.06.015
DO - 10.1053/j.ajkd.2015.06.015
M3 - Article
C2 - 26209544
AN - SCOPUS:84948101032
SN - 0272-6386
VL - 66
SP - 984
EP - 992
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -