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Chronic Kidney Disease Associated With Abnormal Cerebellar Growth in Pediatric Patients
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Key Takeaways
- Pediatric CKD patients show reduced cerebellum volume linked to neurocognitive deficits and lower eGFR, even before dialysis or transplantation.
- The study found lower neurocognitive scores and differential age-related changes in cerebellar gray and white matter in CKD patients compared to controls.
Reductions in cerebellar volume were associated with cognitive deficits and lower kidney function in those with CKD.
Pediatric patients who have chronic kidney disease (CKD) often show reduced cerebellum volume, which is associated with neurocognitive deficits and a lower estimated glomerular filtration rate (eGFR), even prior to kidney dialysis or transplantation. Despite this knowledge, these differences have not been previously examined within the context. Authors of a study published in JAMA Network Open aimed to explore age-related neurodevelopmental trajectories in both adolescent and young adult patients with CKD. Additionally, they looked at age-related trends within brain volumes in relation to neurocognitive outcomes and disease parameters within patients with CKD.
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This case-control study enrolled individuals with CKD who were identified at the University of Iowa through electronic health records between September 2016 and August 2024. Patients were not considered for enrollment if they had any of the following: extreme prematurity (< 30 weeks’ gestational age); seizures and/or receipt of antiepileptic medications; central nervous system anomalies; known chromosomal anomalies; congenital cardiac disease; diagnosed intellectual disability; traumatic brain injury requiring hospitalization; and/or MRI contraindications. Additionally, participants with both normal brain development and presumed normal kidney function (unaffected controls) were recruited alongside participants with CKD based on their age, sex, and maternal education.
All participants completed neurocognitive assessment and structural MRI on the day of the research visit. Additionally, anthropodermic data and blood samples were obtained, and parents or caregivers completed surveys that included the following: participant and family demographics; participant birth, developmental, and medical history; participant educational needs; and family medical history.
A total of 124 individuals aged 6 through 21 years (median age: 12.8 years) were enrolled, consisting of 87 controls and 37 patients with CKD. The majority of patients in both the control (n = 44; 50.6%) and CKD groups (n = 30; 81.1%) were male. The median eGFR was about 71.3 mL/min/1.73 m2 for the CKD group and 101 mL/min/1.73 m2 among controls (β = −29.87; 95% CI, −37.75 to −22.02; P < .001). Age and sex were also retained as main effects in the models.
The findings demonstrated that patients with CKD had scored lower than controls on most neurocognitive measures included in the analyses. The CKD group had 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). Further, volumetric variation in these regions was associated with proxy ratings of executive function in patients who had CKD.
Additionally, there was a significant positive association observed between cerebellar gray matter and eGFR in patients with CKD (β = 0.04; 95% CI, 0.00 to 0.02; P = .01), but not cerebellum white matter (eGFR β = 0.00; 95% CI, −0.01 to 0.02) or amygdala volume (eGFR β = 0.00; 95% CI, −0.11 to 0.02). The association between eGFR and the superior posterior lobe of the cerebellum reached significance (eGFR β = 0.02; 95% CI, 0.01 to 0.03; P = .001). Finally, no other CKD-specific measures were associated with neuroanatomical outcomes in patients with CKD.
One main limitation of the study is its relatively small sample size, according to the authors. Additionally, the participants were mostly White (88%) and male (63.6%); therefore, these results may not be generalizable to other racial groups and/or female patients. The authors urged future research be conducted to assess if these clinical variables and MRI-based assessment of neurodevelopment within CKD are applicable to a more diverse population.
