Chronic Kidney Disease in Children (CKiD) Study

Abstract Chronic Kidney Disease in Children (CKiD) Study PI: Stefan Kiessling Competing Renewal 08/01/23-07/31/28 1. INTRODUCTION 1.1 Overview The Division of Kidney, Urologic, and Hematologic Diseases (DKUHD) of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in collaboration with the National Institute of Child Health and Human Development (NICHD) and the National Heart, Lung and Blood Institute (NHLBI) funded a cooperative agreement including two Clinical Coordinating Centers, a Data Coordinating Center and Central Biochemistry Laboratory to conduct a prospective epidemiological study of children with chronic kidney disease (CKD). The primary goals of this study are to determine the risk factors for decline in kidney function and to define how a progressive decline in kidney function impacts neurocognitive function and behavior; the risk factors for cardiovascular disease; and growth failure and its associated morbidity. 1.2 Specific aims The specific aims are to: 1. Identify novel and traditional renal disease risk factors for the progression of CKD (e.g. decline of GFR) in children, 2. Characterize the impact of a decline in kidney function on neurodevelopment, cognitive abilities, and behavior, 3. Identify the prevalence and evolution of traditional and novel cardiovascular disease risk factors in progressive CKD, and 4. Examine the effects of declining GFR on growth and the treatment of growth failure, and to assess the consequences of growth failure on morbidity in children with CKD. 1.3 Hypotheses The study will address the following hypotheses: 1. Children with mild to moderate chronic kidney disease secondary to structural causes have slower rates of declining GFR compared to those with acquired glomerular disease. 2. Accelerated CKD progression will be associated with a positive family history of kidney disease, black race, Hispanic ethnicity, lower socioeconomic status, elevated systolic and diastolic blood pressure, high nocturnal blood pressure, anemia, periods of accelerated growth, hyperparathyroidism and hyperlipidemia. 3. When indicated, early surgical intervention as well as the prescription and adherence to therapy with angiotensin converting enzyme inhibitors, angiotensin receptor blockers and aldosterone inhibitors will slow CKD progression. 4. Systematic measurements of GFR, centrally measured “true” serum creatinine, centrally based serum Cystatin C and comprehensive clinical data will yield GFR estimating equations with better accuracy and more precision than current formulas based on height and serum creatinine. 5. Declining GFR will be associated with measurable declines in neurocognitive function, behavior and quality of life in children with CKD. The greatest deficit in cognitive function will be seen in children with the longest duration of CKD, the highest stage of CKD and with the lowest hemoglobin levels. 6. Progressive CKD will adversely affect central nervous system conduction pathways, and detectable anatomic changes (white matter changes) will correlate with changes in neurocognitive status and GFR. 7. The prevalence and severity of traditional cardiovascular disease (CVD) risk factors (hypertension, hyperlipidemia) and uremia-related CVD risk factors (inflammation, malnutrition, anemia, hyperparathyroidism), will be associated with the progression of CKD. 8. The prevalence and severity of systemic and nocturnal hypertension will be associated with the decline of GFR and the development of concentric left ventricular hypertrophy (LVH). The prevalence and severity of anemia will be correlated with GFR decline and the development of eccentric LVH. 9. LVH will be responsible for decreased LV diastolic function in children with CKD. 10. Decreased aortic wall compliance will be related to elevated systolic blood pressure, hyperlipidemia, biomarkers of inflammation and increased Ca x P product. 11. Growth failure will be associated with the severity of secondary hyperparathyroidism, biomarkers of inflammation, poor nutrition, extent of GFR decline and early age at onset (i.e., prolonged duration of CKD). 12. Growth failure in children with CKD will be associated with a higher rate of morbidity, including increased hospitalizations, decreased quality of life, poor neurocognitive outcome and increased cardiovascular complications. 13. The response to recombinant human growth hormone (rhGH) treatment will be positively associated with GFR, serum bicarbonate level and nutritional status and negatively correlated with high sensitivity C reactive protein level, and severity of secondary hyperparathyroidism. The proposed cohort study has been designed to measure variables in four scientific domains: kidney, neurocognition, cardiovascular and growth. The protocol was determined to optimize the power of the cohort design whereby levels and changes of exposure of interest temporally precede outcomes.