Early and Stage-Dependent Cardiopulmonary Fitness Impairment in Pediatric CKD

Background: Children with chronic kidney disease (CKD) are at high cardiovascular risk, yet cardiopulmonary fitness is rarely assessed in routine care. Maximal oxygen uptake (VO 2 max) is a powerful prognostic marker, and Z-score–based evaluations may improve early risk stratification. Methods: In this prospective multicenter study, children aged 6–17 years with CKD stages 2-5 (Kidney Disease Improving Global Outcome (KDIGO)) underwent standardized cardiopulmonary exercise testing (CPET). VO 2 max was expressed as Z-scores using contemporary pediatric reference values. Impaired fitness was defined as VO 2 max Z-score < –1.64. Multivariable linear regression was used to identify independent determinants of VO 2 max. Results: Among 88 enrolled patients (mean age 12±4 years, 67% male), 77 completed a valid CPET. Mean VO 2 max Z-score was –1.8±2.1, corresponding to 33.5±9.2 ml/kg/min, i.e. an absolute lowering of approximately 10 mL/kg/min compared with age- and sex-matched reference values. Overall, 57% had impaired fitness. VO 2 max was progressively lower across higher CKD stages ( P<0.001 ). In multivariable analysis, higher VO 2 max was independently associated with higher hemoglobin concentration, better pulmonary function (FEV 1 ), better ventilatory efficiency (VE/VCO 2 slope), and higher ventilatory anaerobic threshold (VAT), explaining 77% of VO 2 max variability. Conclusions: Cardiopulmonary fitness is markedly lower in children with CKD, with a clear stage-dependent decline that is already evident at early disease stages. The magnitude of VO 2 max impairment is substantial and related to potentially modifiable clinical and functional factors, supporting early CPET-based screening and the development of targeted, multidisciplinary rehabilitation in pediatric CKD. Trial Registration: clinicaltrials.gov identifier NCT04897672 and Montpellier University Hospital Institutional Review Board (IRB 202100852).