Children with CKD Show Structural Brain Changes Linked to Cognitive Impairments

By Karen Blum

WASHINGTON, DC – Children with chronic kidney disease (CKD) have structural changes in the brain associated with poorer intelligence, executive function and academic achievement, compared to healthy children without the disease, according to new research from the University of Iowa presented at Kidney Week 2019 in a session entitled, “Pediatric CKD Is Associated with Abnormal White Matter Integrity”.

In a small study of 18 children ages 6-16 with mild to moderate CKD and 22 healthy, age-matched controls, the children with CKD were found to have changes in 11 areas of white matter using MRI and other measures, said lead study author Matthew Solomon, MD, a second-year resident with the university’s Stead Family Department of Pediatrics.

Of note, the CKD patients had less integrity in the rostral medial frontal white matter, associated with lower scores on the Wechsler Intelligence Scale for Children (WISC). They also had lower fractional anisotropy (a symbol of poorer white matter architecture) along the posterior singulate, an area associated with lower scores on a wide range achievement test in the mathematics domain. Finally, they had less integrity in the supermarginal white matter, an area associated with lower executive function in the domain of verbal fluency.

“There appears to be discreet and significant white matter differences in pediatric CKD patients even prior to dialysis or transplant,” Solomon said. “The presence of white matter abnormalities are highly notable in the frontal lobe, internal capsule and even the cerebellum.”

Among the CKD patients studied, the mean estimated glomerular filtration rate (eGFR) was 75, and duration of disease was around 9 years or 115 months. Investigators took MRI scans of the participants’ brains and evaluated differences in fractional anisotropy, a neuroimaging technique that quantifies the restricted diffusion of water molecules in brain tissues. Lower signals equal poorer white matter architecture. More of the children with CKD had a history of premature birth but due to the small sample size, investigators were not able to include this as a covariate, Solomon said.

Brain development is a “long and synchronized process in the healthy child” extending well into the early 20s, Solomon said. Still, there have been few studies to date examining volumetric brain structure and pediatric CKD, he said.

The next steps are to incorporate cortical thickness measures and tractography, a 3-D modeling technique, to further inform understanding of the findings, Solomon said.

“We also need to translate this into a larger sample across time” and include younger children ages 3-5, older adolescent and adults, as well as those with more advanced CKD, senior author Lyndsay Harshman, MD, an assistant professor of pediatrics at the university, told Kidney News Online. Additionally, continuing studies should include more assessments of cytokines and biomarkers to help identify modifiable disease-related factors, she said. “It’s fair to say we have a metric ton of data to unpack.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health.


Resource

1. Abstract TH-OR126 “Pediatric CKD is Associated with Abnormal White Matter Integrity”

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Author:
Karen Blum
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WASHINGTON, DC – Children with chronic kidney disease (CKD) have structural changes in the brain associated with poorer intelligence, executive function and academic achievement, compared to healthy children without the disease, according to new research from the University of Iowa presented at Kidney Week 2019 in a session entitled, “Pediatric CKD Is Associated with Abnormal White Matter Integrity”.

In a small study of 18 children ages 6-16 with mild to moderate CKD and 22 healthy, age-matched controls, the children with CKD were found to have changes in 11 areas of white matter using MRI and other measures, said lead study author Matthew Solomon, MD, a second-year resident with the university’s Stead Family Department of Pediatrics.

Of note, the CKD patients had less integrity in the rostral medial frontal white matter, associated with lower scores on the Wechsler Intelligence Scale for Children (WISC). They also had lower fractional anisotropy (a symbol of poorer white matter architecture) along the posterior singulate, an area associated with lower scores on a wide range achievement test in the mathematics domain. Finally, they had less integrity in the supermarginal white matter, an area associated with lower executive function in the domain of verbal fluency.

“There appears to be discreet and significant white matter differences in pediatric CKD patients even prior to dialysis or transplant,” Solomon said. “The presence of white matter abnormalities are highly notable in the frontal lobe, internal capsule and even the cerebellum.”

Among the CKD patients studied, the mean estimated glomerular filtration rate (eGFR) was 75, and duration of disease was around 9 years or 115 months. Investigators took MRI scans of the participants’ brains and evaluated differences in fractional anisotropy, a neuroimaging technique that quantifies the restricted diffusion of water molecules in brain tissues. Lower signals equal poorer white matter architecture. More of the children with CKD had a history of premature birth but due to the small sample size, investigators were not able to include this as a covariate, Solomon said.

Brain development is a “long and synchronized process in the healthy child” extending well into the early 20s, Solomon said. Still, there have been few studies to date examining volumetric brain structure and pediatric CKD, he said.

The next steps are to incorporate cortical thickness measures and tractography, a 3-D modeling technique, to further inform understanding of the findings, Solomon said.

“We also need to translate this into a larger sample across time” and include younger children ages 3-5, older adolescent and adults, as well as those with more advanced CKD, senior author Lyndsay Harshman, MD, an assistant professor of pediatrics at the university, told Kidney News Online. Additionally, continuing studies should include more assessments of cytokines and biomarkers to help identify modifiable disease-related factors, she said. “It’s fair to say we have a metric ton of data to unpack.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health.


Resource

1. Abstract TH-OR126 “Pediatric CKD is Associated with Abnormal White Matter Integrity”

Date:
Friday, November 8, 2019