BACKGROUND: Sodium-23 magnetic resonance imaging ((23)Na MRI) allows non-invasive assessment of tissue sodium concentration ([Na(+)]). Age and chronic kidney disease (CKD) are associated with increased tissue [Na(+)] in adults, but limited information is available pertaining to children and adolescents. We hypothesized that pediatric CKD is associated with altered tissue [Na(+)] compared to healthy controls. METHODS: This was a case-control exploratory study on healthy children and adults and pediatric CKD patients. Study participants underwent an investigational visit, blood/urine biochemistry, and leg (23)Na MRI for tissue [Na(+)] quantification (whole leg, skin, soleus muscle). CKD was stratified by etiology and patients' tissue [Na(+)] was compared against healthy controls by computing individual Z-scores. An absolute Z-score \textgreater 1.96 was deemed to deviate significantly from the mean of healthy controls. Pearson correlation was used to compute the associations between tissue [Na(+)] and kidney function. RESULTS: A total of 36 pediatric participants (17 healthy, 19 CKD) and 19 healthy adults completed the study. Healthy adults had significantly higher tissue [Na(+)] compared with pediatric groups; conversely, no significant differences were found between healthy children/adolescents and CKD patients. Four patients with glomerular disease and one kidney transplant recipient due to atypical hemolytic-uremic syndrome had elevated whole-leg [Na(+)] Z-scores. Reduced whole-leg [Na(+)] Z-scores were found in two patients with tubular disorders (Fanconi syndrome, proximal-distal renal tubular acidosis). All tissue [Na(+)] measures were significantly associated with proteinuria and hypoalbuminemia. CONCLUSIONS: Depending on etiology, pediatric CKD was associated with either increased (glomerular disease) or reduced (tubular disorders) tissue [Na(+)] compared with healthy controls. A higher resolution version of the Graphical abstract is available as Supplementary information.