Table 1.

Summary of CKiD Neurocognitive and Psychosocial Studies from 2010–2021 (n = 22 Studies)

Study	Sample	Measures	Findings
Neurocognitive
Hooper et al, 2011	n = 368 children, ages 6–16 yrs.	WASI, WIAT-II Screening, CPT- II, BRIEF (parent), selected tasks from D-KEFS	21% to 40% deemed to be at risk for neurocognitive dysfunction. Elevated proteinuria was associated with lower IQ and increased attention problems. Higher eGFR was associated with preserved executive functions.
Lande et al, 2011	n = 383; 132 (34%) had elevated blood pressure.	WASI, WIAT-II Screening, CPT- II, BRIEF (parent), D-KEFS (selected tasks)	Higher casual blood pressure associated with lower nonverbal IQ.
Hartung et al, 2014	n = 22 ARPKD patients compared to n = 44 children with other causes of CKD matched on eGFR, age at study entry, and age at diagnosis.	WASI or WPPSI-R or MSEL, WIAT-II Screening, CPT-II or K- CPT, BRIEF (parent), BASC-2 (parent)	Children with ARPKD in the CKiD sample showed intact neurocognitive abilities and average parent ratings of social- behavioral when compared to normative expectations and other children with CKD.
Mendley et al, 2015	n = 340, ages 6 to 21 yrs. (median age = 13.0 yrs.); median duration of CKD = 10 yrs.	CPT-II, D-KEFS Tower Task, Digit Span Backward task from the age-appropriate Wechsler Intelligence Scale	Longer duration of CKD associated with lower attention and executive functions.
Hooper et al, 2016	n = 124 children, ages 12 to 68 months (median = 3.7 years)	WPPSI-III, MSEL, K-CPT, ABAS-II	Average level of development/IQ, but distribution was skewed toward lower cognitive abilities. 20% to 30% performed in the at-risk range on the neurocognitive measures, and 37% received ratings in the at- risk range for adaptive behavior problems. Higher eGFR associated with higher cognitive functioning.
Lande et al, 2016	n = 650, with a mean follow-up period of 4.0 yrs.	D-KEFS Category Switching	More variable visit-to-visit systolic blood pressure associated with verbal set-shifting abilities.
Verbitsky et al, 2017	n = 389 noncarriers and n = 31 children with genomic disorders	WASI-II, WIAT-II Screening, BRIEF (Parent), BASC-2 (parent)	A subset of children with CKD are diagnosed with genomic disorders that predispose them to both kidney abnormalities and neurocognitive impairment.
Knight et al, 2017	n = 34 children with lupus nephritis; n = 171 children with other forms of glomerular disease	WASI, WIAT-II Screening, CPT- II, BRIEF (parent), D-KEFS (selected tasks), BASC-2 (parent)	Children with lupus nephritis showed intact neurocognitive abilities when compared to other children with CKD. Current prednisone use related to poorer attention and better adaptive skills. An interaction between current prednisone use and lupus nephritis for internalizing problems was noted, with worse parent-reported internalizing problems in children with lupus nephritis on prednisone.
Matsuda-Abedini et al, 2018	n = 49, 29 with CKD, including kidney transplant (mean age 14.4 yrs.) and 20 healthy controls (mean age 13.7 yrs.)	sMRI using fractional anisotropy maps calculated from diffusion tensor imaging X V	Brain abnormalities demonstrated by focal and multifocal white matter injury in the anterior limb of the internal capsule.
Harshman et al, 2019	n = 319; median age = 12.7 yrs.; median duration of CKD = 10.2 yrs.	WIAT-II Screening	Low total academic achievement in 34% percent of the sample. No significant effect of CKD-related medical variables on academic achievement. Mathematics had the lowest scores. Low achievement was related to days of missed school and presence of individualized education plan.
Ruebner et al, 2019	n = 412, median age = 15.4 yrs.	WASI, WIAT-II Screening, CPT- II, BRIEF (parent), D-KEFS (selected tasks)	Small amounts of blood lead are detected in the CKiD sample, and these small amounts were associated with lower IQ and poor attention abilities.
Harshman et al, 2020	n = 865, with about 22% with low bicarbonate at study entry.	WASI, WIAT-II Screening, CPT- II, BRIEF (parent), D-KEFS (selected tasks), WISC-IV- Integrated	Blood pressure variability x low levels of bicarbonate contributed to lower parent ratings of executive functions.
Kuperferman et al, 2020	Of 891 subjects, 5 (0.56%) had a confirmed stroke prior to study entry. Median time at risk was 15.7 yrs.	WASI, WIAT-II Screening, CPT- II, BRIEF (parent), D-KEFS (selected tasks)	Incidence rate of approximately 36.8 per 100,000. Presence of ischemic stroke associated with uniformly lower neurocognitive functioning.
Yokoyama et al, 2020	n = 702 for whom baseline plasma FGF-23 and neurocognitive testing were performed; ages 6 to 16 yrs.	WASI, CPT-II, D-KEFS (selected tasks)	Higher plasma FGF-23 level was associated with lower performance in executive function and attention regulation. This finding was independent of eGFR.
Emotional-Behavioral
Kogon et al, 2016	n = 344 school-age children, ages 6 to 17 yrs., median age = 13 yrs.; 7% carried a prior diagnosis of depression; 8 participants were receiving pharmacological treatment at the time of the visit.	Child Depression Inventory (Child), Pediatric Inventory of Quality of Life Core Scales (parent and youth), WASI-II, WIAT-II Screening	5% rate of elevated depression symptoms, and another 2% were being treated for depression. Depressive symptoms were not associated with change in eGFR, but were related to lower IQ, lower academic achievement, and lower ratings of quality of life.
Johnson et al, 2020	n = 845, ages 2 to 18 yrs.; median age at study entry = 11.8 yrs.	BASC-2 (parent)	Longitudinal parent ratings of behavioral functioning of their children were within the average range for their chronological age, with little change occurring over time. Higher proportions of children were within the at-risk range on one or more clinical or adaptive behavior scale. Proteinuria and persistent hypertension were associated with parent-reported attention, and seizure history was related to internalizing symptoms.
Quality of Life
Gerson et al, 2010	n = 402, median age = 11 yrs.; mean duration of CKD = 7.4 yrs.	Pediatric Inventory of Quality of Life Core Scales (parent and youth)	Parent and youth ratings were significantly more impaired in physical, school, social, and emotional domains when compared to data from healthy children after adjusting for demographic and CKD-related factors. Better scores in physical, emotional, and social domains were related to longer disease duration and older age. Older age related to lower school quality of life ratings.
Roumelioti et al, 2010	n = 301; median age = 13.9 yrs.	Pediatric Inventory of Quality of Life Core Scales (parent and youth) (selected sleep items)	Severity of CKD was associated with increased reports of weakness, fatigue, daytime sleepiness, and lower overall quality of life ratings.
Al-Uzri et al, 2013	n = 483, median age = 10.4 yrs.	Pediatric Inventory of Quality of Life Core Scales (parent and youth)	Use of growth hormone and subsequent growth in height was significantly related to more positive parent report of physical and social quality of life.
Wong et al, 2016	n = 551 contributing to 2,376 visits; Normotensive n = 384, Elevated Blood Pressure n = 164, with n = 101 on hypertensive medication; median age = 11.5 yrs.; CKD duration = 6.4 yrs.	Pediatric Inventory of Quality of Life Core Scales (parent and youth)	Elevated blood pressure was significantly related to lower parent and child ratings of health-related quality of life.
Carlson et al, 2020	n = 733; median age = 11.0 yrs.; median duration of CKD was 8 years.	Pediatric Inventory of Quality of Life Core Scales (parent and youth)	Longitudinal analysis showed little change in perceived quality of life over time. Longer duration of CKD was associated with higher child-rated quality of life, and anemia was related to lower physical and emotional functioning.
Ferris et al, 2021	n = 734; median age = 11 years; disease duration = 8 years	Pediatric Inventory of Quality of Life Core Scales (parent and youth); medication counts	Average parent quality of life scores for younger children were higher than those for older children, but ratings declined more with increased medication counts than parent ratings for older children.

WASI-II = Wechsler Abbreviated Scale of Intelligence (2^nd edition); WIAT-II = Wechsler Individual Achievement Test (2^nd edition); CPT-II = Conners’ Continuous Performance Test-II; K-CPT = Kiddie Continuous Performance Test; BRIEF = Behavior Rating Inventory of Executive Functions; D-KEFS = Delis-Kaplan Executive Function System; WPPSI-R = Wechsler Preschool and Primary Scale of Intelligence-Revised; MSEL = Mullen Scale of Early Learning; BASC-2 = Behavior Assessment System for Children (2^nd edition); ABAS-II = Adaptive Behavior Assessment Scale (2^nd edition); sMRI = structural magnetic resonance imaging; WISC-IV-I = Wechsler Intelligence Scale for Children (4^th edition) – Integrated