Chronic kidney disease (CKD) and its metabolic derangements substantially affect the well-being of children. In order to define the nature, magnitude, and temporal evolution of the adverse effects of progressive CKD, we propose to conduct a prospective study of CKD in children to determine (1) risk factors for accelerated decline in renal function; (2) incidence, nature, magnitude and temporal evolution of impaired brain function and structure; (3) prevalence of risk factors for cardiovascular disease (CVD); and (4) implications of growth failure and its treatment on morbidity. The Prospective Study of Chronic Kidney Disease in Children (C-Kid) is a longitudinal, observational study of 600 children, aged < 19 yrs with mildly to moderately impaired kidney function (estimated glomerular filtration rate (GFR) 30-75 ml/min/1.73m2). The follow-up period will be 2.5 to 4.5 years. At enrollment, and at annual visits thereafter, selected exposures will be obtained on participants, including sociodemographic characteristics, family history, health care utilization, environmental exposures and medication use using standardized questionnaires. Standardized blood pressure, growth and nutritional assessments, metabolic status, measures of anemia, dyslipidemia, measures of microinflammation, insulin resistance and proteinuria will also be measured. Level of kidney function (GFR) will be measured annually by plasma disappearance of iohexol. The primary outcomes of interest will be the temporal evolution of subclinical measures and clinical events associated with CKD progression as measured by decline in GFR, growth failure and its treatment, neurocognitive and behavioral deficits and cardiovascular disease, specified in our aims below. Potential analyses that could be conducted using the C-Kid infrastructure to explore risk-factor disease relationships include traditional prospective cohort analyses where putative risk factors are measured in participants at baseline; nested case-control studies in which laboratory studies are performed on stored baseline specimens in cases (e.g. rapid progressors) and appropriately matched controls (e.g. non-progressors); and cross-cohort analyses utilizing parallel cohorts.
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