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

Abstract

Importance: 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.

Objective: 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.

Design, setting, and participants: 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.

Exposures: Neurocognitive testing; 3-T magnetic resonance imaging.

Main outcomes and measures: 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.

Results: 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).

Conclusions and relevance: 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.