Box 3.

Summary of Novel Findings from CKiD study

1. Identify novel and traditional risk factors for the progression of CKD New bedside CKiD formula to estimate GFR in children age 1–16 years with GFR from 15 to 75 ml/min/1.73m2 (see Box 1). New GFR estimating formula using enzymatic creatinine shows 25% reduction in eGFR from Schwartz equation based on the Jaffe method for measuring serum creatinine. Race, lower iGFR, and glomerular cause of CKD are independently associated with level of proteinuria. More than 30% of the children met the NKF-KDOQI definition for anemia in pediatric patients, hemoglobin concentration < 5th percentile of normal when adjusted for age and sex. Hemoglobin level declines in a linear manner below a threshold iGFR of 43 ml/min/1.73m2, independent of age, race, sex, and underlying diagnosis. African American children with CKD have lower hemoglobin levels and a higher prevalence of anemia than Caucasian children despite no difference in erythropoietin or iron therapy.

2. Characterize the impact of a decline in kidney function on neurodevelopment, cognitive abilities, and behavior At study entry, 21% to 40% of children with CKD scored more than 1 SD below norm on a variety of neurocognitive tests. Children with proteinuria (UPCR >2) scored lower on verbal IQ, full-scale IQ, and attention variability compared to those without elevated proteinuria. High blood pressure (SBP and/or DBP ≥ 90th percentile) is independently associated with lower scores on performance IQ, which tests visual-spatial organization and construction, and non-verbal reasoning. HRQoL is adversely affected compared to healthy controls early in the course of CKD. Urinary incontinence occurs in almost 30% of children with CKD and is associated with impaired HRQoL. Sleep and fatigue problems in children with CKD are associated with decreased HRQoL.

3. Identify the prevalence and the evolution of cardiovascular disease risk factors in children with CKD Nephrotic range proteinuria is significantly associated with elevated DBP. African American children had a higher risk of having elevated blood pressures at entry into the CKiD study. Children with hypertension not receiving ACE inhibitor and/or ARB medication have an increased prevalence of uncontrolled BP. Use of calcium channel blockers is more common in children with uncontrolled BP. Strong association between the presence of hypertension and LVH. Likelihood of LVH was 4 times higher in children with masked hypertension compared to normotensive children.

4. Examine the effects of declining GFR on growth and assess the consequences of growth failure on morbidity in children with CKD Low birth weight and being small for gestational age at birth are novel risk factors for short stature in children with CKD. Short stature in children with CKD is associated with lower scores in the physical functioning domain of the PedsQL.

Abbreviations: ACE: angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; LVH, left ventricular hypertrophy; HRQoL, health-related quality of life; PedsQL, Pediatric Inventory of Quality of Life Core Scales; DBP, diastolic blood pressure; SBP, systolic blood pressure; IQ, intelligence quotient; SD, standard deviation; iGFR, iohexol-based glomerular filtration rate; eGFR, estimated glomerular filtration rate; GFR, glomerular filtration rate; CKD, chronic kidney disease; CKiD, CKD in Children. NKF-KDOQI, National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative.