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Age-Related Changes in Brain Structure in Pediatric Chronic Kidney Disease
Journal article   Open access   Peer reviewed

Age-Related Changes in Brain Structure in Pediatric Chronic Kidney Disease

Ellen van der Plas, Eric Nelson, Brian Becknell, Anne E Dawson, Camille S Wilson, Jeffrey D Dawson, Joseph L Alge and Lyndsay A Harshman
JAMA network open, Vol.8(2), e2457601
02/03/2025
DOI: 10.1001/jamanetworkopen.2024.57601
PMCID: PMC11791706
PMID: 39899296
url
https://doi.org/10.1001/jamanetworkopen.2024.57601View
Published (Version of record) Open Access

Abstract

Pediatric patients with chronic kidney disease (CKD) exhibit reduced cerebellum volume, which is associated with neurocognitive deficits and a lower estimated glomerular filtration rate (eGFR), even before dialysis or transplantation. These differences have not been examined within the context of age-related brain changes during childhood to early adulthood. To evaluate differences in age-related neurodevelopmental changes in patients with CKD compared with control participants and to investigate associations between regional neuroanatomy, functional outcomes, and disease-related variables. Case-control study of individuals aged 6 through 21 years with and without CKD at an academic medical center in Iowa City, Iowa, from September 2016 to August 2024. Neurocognitive testing; 3-T magnetic resonance imaging. Participants completed standardized neurocognitive assessments and quantitative neuroanatomical scans. Brain regions of interest (ROIs) were analyzed for volumetric differences using automated pipelines. Multivariable linear models assessed neurocognitive and neuroanatomical differences between groups, including an age × group interaction for ROI analyses. The sample included 124 individuals (mean [SD] age, 12.8 [4.5] years; 74 [59.7%] male), including 87 control participants (44 [50.6%] male) and 37 participants with CKD (30 [81.1%] male). The mean (SD) eGFR was 71.3 [25.5] mL/min/1.73 m2 for the CKD group. Participants with CKD scored lower than control participants on most neurocognitive measures included in the analyses. The CKD group showed differential age-related changes in cerebellar gray matter (β = -0.10; 95% CI, -0.18 to -0.01; Cohen f = 0.22) and white matter (β = -0.09; 95% CI, -0.19 to -0.00; Cohen f = 0.19). The age × group interaction approached but did not reach significance for amygdala volume (β = 0.09; 95% CI, -0.01 to 0.19; Cohen f = 0.18; P = .06). Volumetric variation in these regions was associated with proxy ratings of executive function in patients with CKD. A significant, positive association between cerebellar gray matter and eGFR was observed in the CKD group (β = 0.04; 95% CI, 0.00 to 0.02; P = .01). In this case-control study, age-related neurodevelopmental differences were observed in pediatric patients with CKD compared with healthy peers. Reductions in cerebellar volume were associated with cognitive deficits and lower kidney function. These findings underscore the importance of monitoring neurodevelopmental trajectories in children with CKD, as early interventions may be necessary to mitigate cognitive impairments associated with CKD.
 Magnetic Resonance Imaging Adolescent Age Factors Brain - diagnostic imaging Brain - pathology Brain - physiopathology Case-Control Studies Child Female Glomerular Filtration Rate Humans Male Neuropsychological Tests - statistics & numerical data Renal Insufficiency, Chronic - physiopathology Young Adult

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