Neuron-specific enolase and brain-derived neurotrophic factor as developmental neurovascular markers in chronic kidney disease and kidney transplantation

BACKGROUND: Chronic kidney disease (CKD) in children exposes the developing brain to uremic and vascular insults, yet blood-based markers of the pediatric kidney-brain axis remain underexplored. We characterized neuron-specific enolase (NSE) and brain-derived neurotrophic factor (BDNF) across the spectrum of pediatric kidney disease. METHODS: Prospective cohort of 75 children with measured GFR: 12 comparators with normal kidney function, 31 with non-dialysis CKD stages G2-G5, and 32 kidney transplant recipients (KTx). Biomarkers were measured by ELISA at baseline and after 3.2 years. Cross-sectional and longitudinal analyses adjusted for age and group. RESULTS: NSE correlated inversely with age (r = - 0.46, p < 0.001) and did not differ between groups after age adjustment. NSE-age slopes were comparable in comparators and CKD but flat in transplanted children, indicating loss of the developmental decline in this group. BDNF correlated positively with measured GFR (r = 0.31, p = 0.018) and was lower in CKD than in comparators, consistent with reduced neurotrophic reserve in pediatric uremia. CONCLUSIONS: Circulating NSE in childhood reflects developmental stage rather than CKD status. Group comparisons in pediatric biomarker studies require age adjustment. Transplantation alters the NSE-age relationship beyond what kidney function explains. BDNF tracks kidney function in pediatric CKD. Age-stratified reference intervals are required before either marker can guide clinical decisions.