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J Am Soc Nephrol. 2017 Aug;28(8):2303-2309. doi: 10.1681/ASN.2016101108. Epub 2017 Mar 27.

Genomic Disorders and Neurocognitive Impairment in Pediatric CKD.

Author information

1
Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, New York.
2
Division of Pediatric Nephrology, Nationwide Children's Hospital, Columbus, Ohio.
3
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland; Departments of.
4
Allied Health Sciences and.
5
Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
6
Division of Pediatric Nephrology, University of New Mexico Children's Hospital, Albuquerque, New Mexico.
7
Division of Pediatric Nephrology, Children's Mercy Hospital, Kansas City, Missouri; Departments of.
8
Pediatrics and.
9
Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; and.
10
Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
11
Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, New York; ag2239@columbia.edu.

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

PMID:
28348065
PMCID:
PMC5533237
DOI:
10.1681/ASN.2016101108
[Indexed for MEDLINE]
Free PMC Article

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