PEDIATRIC NEPHROLOGY, 2026 (SCI-Expanded, Scopus)
BackgroundChronic kidney disease (CKD), characterized by chronic inflammation and uremic toxicity, represents a state of premature immune aging. However, data on T-cell receptor (TCR) repertoire alterations in pediatric CKD are limited. The TCR variable beta (V beta) region defines distinct T-cell subfamilies generated by V(D)J recombination and reflects T-cell repertoire diversity and clonal composition. Alterations in TCR V beta distribution indicate repertoire remodeling associated with chronic antigenic stimulation and immune aging beyond quantitative lymphocyte changes. This study aimed to characterize TCR V beta family repertoire in children with advanced CKD and explore their associations with clinical and biochemical parameters.MethodsIn this single-center, cross-sectional study, 35 children with CKD stages 3b-5 (21 non-dialysis, 14 dialysis) and 15 age- and sex-matched healthy controls were enrolled. Peripheral blood lymphocyte subsets and TCR V beta 1-V beta 23 distributions were assessed by flow cytometry and compared with clinical and laboratory measures. Group comparisons were performed using the Mann-Whitney U test, and associations were assessed using Spearman correlation analysis.ResultsChildren with CKD exhibited a skewed TCR V beta repertoire, with reduced expression of V beta 9 and V beta 11 and increased V beta 17 (p = 0.041, 0.001, 0.014, respectively) with corresponding moderate-to-large effect sizes (r = 0.37, r = 0.61, and r = 0.44). Dialysis patients showed lower V beta 11 and higher V beta 12 expression compared with non-dialysis patients (p = 0.034 and p = 0.048), with large effect sizes (r = 0.68 and r = 0.66). Reduced V beta 9 correlated with low BMI and higher proteinuria, and reduced V beta 11 correlated with hypoalbuminemia, whereas elevated V beta 12 was associated with higher CRP and creatinine levels. Total lymphocyte counts were preserved, although dialysis patients demonstrated a higher CD4/CD8 ratio.ConclusionsPediatric CKD is associated with selective and non-uniform remodeling of the T-cell repertoire, reflecting premature immune senescence. The associations between TCR V beta alterations, inflammation, and nutritional markers suggest synergistic effects of uremic toxicity and protein-energy imbalance on immune aging, warranting larger mechanistic studies.Graphical AbstractA higher resolution version of the Graphical abstract is available as Supplementary information.