Neurocognitive and Educational Outcomes in Children and Adolescents with CKD: A Systematic Review and Meta-Analysis

Abstract

Background and objectives: Poor cognition can affect educational attainment, but the extent of neurocognitive impairment in children with CKD is not well understood. This systematic review assessed global and domain-specific cognition and academic skills in children with CKD and whether these outcomes varied with CKD stage.

Design, setting, participants, & measurements: Electronic databases were searched for observational studies of children with CKD ages 21 years old or younger that assessed neurocognitive or educational outcomes. Risk of bias was assessed using a modified Newcastle-Ottawa scale. We used random effects models and expressed the estimates as mean differences with 95% confidence intervals stratified by CKD stage.

Results: Thirty-four studies (25 cross-sectional, n=2095; nine cohort, n=991) were included. The overall risk of bias was high because of selection and measurement biases. The global cognition (full-scale intelligence quotient) of children with CKD was classified as low average. Compared with the general population, the mean differences (95% confidence intervals) in full-scale intelligence quotient were -10.5 (95% confidence interval, -13.2 to -7.72; all CKD stages, n=758), -9.39 (95% confidence interval, -12.6 to -6.18; mild to moderate stage CKD, n=582), -16.2 (95% confidence interval, -33.2 to 0.86; dialysis, n=23), and -11.2 (95% confidence interval, -17.8 to -4.50; transplant, n=153). Direct comparisons showed that children with mild to moderate stage CKD and kidney transplants scored 11.2 (95% confidence interval, 2.98 to 19.4) and 10.1 (95% confidence interval, -1.81 to 22.0) full-scale intelligence quotient points higher than children on dialysis. Children with CKD also had lower scores than the general population in executive function and memory (verbal and visual) domains. Compared with children without CKD, the mean differences in academic skills (n=518) ranged from -15.7 to -1.22 for mathematics, from -9.04 to -0.17 for reading, and from -14.2 to 2.53 for spelling.

Conclusions: Children with CKD may have low-average cognition compared with the general population, with mild deficits observed across academic skills, executive function, and visual and verbal memory. Limited evidence suggests that children on dialysis may be at greatest risk compared with children with mild to moderate stage CKD and transplant recipients.

Keywords: Adolescent; Bias; Child; Cognition; Cohort Studies; Confidence Intervals; Cross-Sectional Studies; Education; Epidemiology and outcomes; Executive Function; Humans; Intelligence; Mathematics; Memory; Neurocognition; Reading; Renal Insufficiency, Chronic; Transplant Recipients; chronic kidney disease; dialysis; kidney transplantation; pediatrics; transplant outcomes.

Figure 1.

Preferred reporting items for systematic reviews and meta-analyses flowchart. Thirty-four studies were included for systematic review (25 cross-sectional, 9 cohort). IQ, intelligence quotient.

Figure 2.

Significant deficits observed in children with CKD. A shows full-scale intelligence quotient (IQ) between children with and without CKD. B shows verbal and performance IQ between children with and without CKD. 95% CI, 95% confidence interval; df, degree of freedom; IV, inverse variance; SE, SEM.

Figure 2.

Significant deficits observed in children with CKD. A shows full-scale intelligence quotient (IQ) between children with and without CKD. B shows verbal and performance IQ between children with and without CKD. 95% CI, 95% confidence interval; df, degree of freedom; IV, inverse variance; SE, SEM.

Figure 2.

Significant deficits observed in children with CKD. A shows full-scale intelligence quotient (IQ) between children with and without CKD. B shows verbal and performance IQ between children with and without CKD. 95% CI, 95% confidence interval; df, degree of freedom; IV, inverse variance; SE, SEM.

Figure 3.

Risk of bias assessment. The overall risk of bias was high.

Figure 4.

Subgroup analyses of full-scale intelligence quotient in children with and without CKD (mild to moderate stage CKD). 95% CI, 95% confidence interval; df, degree of freedom; IV, inverse variance; SE, SEM.