Noninvasive Quantification of Tissue Sodium Concentration in the Kidney Disease Spectrum using 23Na Magnetic Resonance Imaging

Chronic kidney disease (CKD), especially when requiring kidney replacement therapy (hemodialysis (HD) and peritoneal dialysis (PD)), is associated with extracellular water expansion with increased total body sodium. Sodium can also be accumulated in tissues independently of extracellular water. Sodium-23 magnetic resonance imaging (23Na MRI) can quantify the concentration of sodium nuclei in tissues. Applied to the human leg, quantification of tissue sodium concentrations mainly at the skin and muscle level is possible. We hypothesized that increased tissue sodium concentrations exert toxic effects in CKD and dialysis. We aimed to (1) compare tissue sodium concentrations in adults, children and adolescents with CKD, HD and PD against healthy individuals, (2) identify their predictors, (3) understand their connection to left ventricular structure in patients receiving HD and (4) observe their relationship with adverse cardiovascular events and mortality in patients receiving HD and PD. Tissue sodium concentrations were increased in adult patients receiving HD and PD, with respect to healthy individuals. In children and adolescents with CKD, tissue sodium concentrations varied depending on CKD etiology, suggesting kidney disorders can be associated with either sodium wasting or accumulation. Tissue sodium concentrations were associated with older age and overweight in healthy individuals; in patients with CKD and receiving dialysis, hypoalbuminemia was an important predictor of tissue sodium concentrations. In pediatric CKD, proteinuria was also positively associated with tissue sodium concentrations, suggesting a role of proteinuria in increased sodium reabsorption. In patients receiving HD, dialysate sodium concentration was strongly positively associated with skin sodium concentrations. In patients receiving HD, tissue sodium concentrations were associated with left ventricular hypertrophy and dilatation, with tissue sodium concentrations being highest in patients with a dilated heart. Skin sodium concentration was associated with major cardiovascular adverse events and mortality in patients receiving HD or PD. These findings expand our understanding on the toxicity of sodium in CKD and point out critical issues of current dialysis treatment practices. Future studies should explore improved technical applications of 23Na MRI and experiment with new therapies and treatment strategies to reduce tissue sodium concentration in patients with CKD and those receiving dialysis.