Genomic Disorders and Neurocognitive Impairment in Pediatric CKD

Abstract

Children with CKD are at increased risk for neurocognitive impairment, but whether neurocognitive dysfunction is solely attributable to impaired renal function is unclear. Data from the CKD in Children Study Chronic Kidney Disease in Children (CKiD) Study indicate that a subset of children with CKD have unsuspected genomic disorders that predispose them to organ malformations and neurocognitive impairment. We therefore tested whether the CKiD Study participants with genomic disorders had impaired neurocognitive performance at enrollment. Compared with noncarriers (n=389), children with genomic disorders (n=31) scored significantly poorer on all measures of intelligence, anxiety/depressive symptoms, and executive function (differences of 0.6-0.7 SD; P=1.2×10-3-2.4×10-4). These differences persisted after controlling for known modifiers, including low birth weight, maternal education, seizure disorder, kidney disease duration, and genetically defined ancestry. The deleterious effect of genomic disorders on neurocognitive function was significantly attenuated in offspring of mothers with higher education, indicating the potential for modification by genetic and/or environmental factors. These data indicate that impaired neurocognitive function in some children with CKD may be attributable to genetic lesions that affect both kidney and neurocognitive development. Early identification of genomic disorders may provide opportunity for early diagnosis and personalized interventions to mitigate the effect on neurocognitive function.

Keywords: Epidemiology and outcomes; chronic kidney disease; human genetics; pediatric nephrology.

Copyright © 2017 by the American Society of Nephrology.

Figures

Figure 1.

GD carrier status is associated with impaired NC scores. Violin plots show the distribution of IQ, internalizing problems, and GEC scores among GD carriers (gray) and noncarriers (white). Superimposed box plots show median, interquartile range, and whiskers extending to nonoutlier highest and lowest values per group.

Figure 2.

Opposing effect of maternal education level and GD carrier status on IQ. Violin plots show the distribution of IQ among GD carriers (gray) and noncarriers (white) and among children to mothers with any level of college education (left panel) or only high school education (right panel). Superimposed box plots show median, interquartile range, and whiskers extending to nonoutlier highest and lowest values per group.