Abstract
Background
The impact of pediatric chronic kidney disease (pCKD) on the brain remains poorly defined. The objective of this study was to compare brain morphometry between children with early-stage pCKD and typically developing peers using structural magnetic resonance imaging (MRI).
Methods
The sample age range was 6–16 years. A total of 18 children with a diagnosis of pCKD (CKD stages 1–3) due to congenital anomalies of the kidney and urinary tract and 24 typically developing peers were included. Volumetric data from MRI and neurocognitive testing were compared using linear models including pCKD status, age, maternal education level, and socioeconomic status.
Results
Cerebellar gray matter volume was significantly smaller in pCKD, t(38) = −2.71, p = 0.01. In contrast, cerebral gray matter volume was increased in pCKD, t(38) = 2.08, p = 0.04. Reduced cerebellum gray matter volume was associated with disease severity, operationalized as estimated glomerular filtration rate (eGFR), t(14) = 2.21, p = 0.04 and predicted lower verbal fluency scores in the pCKD sample. Enlarged cerebral gray matter in the pCKD sample predicted lower scores on mathematics assessment.
Conclusions
This study provides preliminary evidence for a morphometric underpinning to the cognitive deficits observed in pCKD.
Impact
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The impact of pediatric chronic kidney disease (CKD) on the brain remains poorly defined, with no data linking brain morphometry and observed cognitive deficits noted in this population.
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We explored the relationship between brain morphometry (using structural magnetic resonance imaging), cognition, and markers of CKD.
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Cerebellar and cerebral gray matter volumes are different in early CKD. Volumetric decreases in cerebellar gray matter are predicted by lower eGFR, suggesting a link between disease and brain morphometry.
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Reduced cerebellar gray matter predicted lower verbal fluency for those with pCKD. Enlarged cerebral gray matter in the pCKD sample predicted lower mathematics performance.
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Acknowledgements
This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK110443 to L.A.H.).
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Research idea and study design: L.A.H., P.D.B., S.L.F., and P.C.N.; data acquisition: M.S., M.N., T.R.K., L.A.H.; data analysis/interpretation: M.S., L.A.H., K.E.L., E.v.P., T.R.K., J.L.S., A.L.C., P.C.N.; supervision or mentorship: L.A.H., P.C.N., P.D.B., and S.L.F. Primary responsibility to drafting the paper: M.S., L.A.H., E.v.P., J.L.S., M.N., P.C.N., P.D.B., and S.L.F. All authors contributed important intellectual content during iterative manuscript drafts or revisions, accepts personal accountability for the author’s own contributions, reviewed the document submitted for review, and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
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Solomon, M.A., van der Plas, E., Langbehn, K.E. et al. Early pediatric chronic kidney disease is associated with brain volumetric gray matter abnormalities. Pediatr Res 89, 526–532 (2021). https://doi.org/10.1038/s41390-020-01203-w
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DOI: https://doi.org/10.1038/s41390-020-01203-w
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