Impact of pediatric chronic kidney disease on brain integrity: A combined volumetric and MR spectroscopy analysis.

PURPOSE: Investigation of structural brain volume alterations and metabolic changes in stages 3-5 pCKD using volumetric MRI with MR spectroscopy.

METHODS

In this cross-sectional study, 63 children with pCKD (stages 3-5; age range: 2-12 years), including 29 on dialysis and 34 not on dialysis, were compared to 63 age- and sex-matched healthy controls (age range: 3-11 years). All participants underwent brain MRI with automated volumetric segmentation (volBrain) and single-voxel spectroscopy to quantify N-acetylaspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr) ratios in the basal ganglia and pons. Group comparisons and correlation analyses between brain volumes and metabolite ratios were performed using independent t-tests, one-way ANOVA, Pearson/Spearman correlation, and analysis of covariance (ANCOVA) with grey matter volume as a covariate.

RESULTS

Patients with pCKD (stage 3-5) demonstrated significant, widespread reductions in brain volume, affecting total brain, grey matter, cerebrum, cerebellum, and subcortical structures compared to controls (p < 0.05), with the most pronounced changes in the dialysis subgroup. Metabolically, pCKD patients showed significantly decreased NAA/Cr in the basal ganglia and increased Cho/Cr in both the basal ganglia and pons (p < 0.01), alterations that were most severe in dialysis patients. Crucially, pontine metabolite ratios correlated strongly with brain volumes: NAA/Cr showed a significant negative correlation (p = 0.01), while Cho/Cr showed a significant positive correlation(p = 0.014). Metabolic basal ganglia changes remained statistically significant after covariation for grey matter volume (p ≤ 0.001).

CONCLUSION

In pediatric patients with moderate-to-severe CKD (stages 3-5), the disease is associated with widespread brain atrophy and region-specific metabolic alterations, which are exacerbated by dialysis. The observed correlation between pontine metabolite alterations and global brain volumes generates the hypothesis that brainstem pathology may reflect or contribute to brain volume changes. The combined use of volumetric MRI and MR spectroscopy provides a powerful, comprehensive biomarker for assessing CKD-related brain injury.

CLINICAL RELEVANCE STATEMENT: This study demonstrates that pediatric chronic kidney disease is associated with significant, measurable alterations in brain structure and metabolism. The findings underscore the necessity for integrating neurological surveillance into routine CKD management and establish a foundation for future trials to test neuroprotective strategies aimed at mitigating this previously underappreciated comorbidity.