Supplementary Material for: Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease

<b><i>Background:</i></b> Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation. <b><i>Objectives:</i></b> We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways. <b><i>Methods:</i></b> We studied 23 CKD stage 5 patients and 11 healthy controls (HC). Tissue sodium concentration was assessed using ²³Sodium magnetic resonance (MR) imaging. Hydration status was evaluated using bioimpedance spectroscopy. A panel of inflammatory and endothelial biomarkers was also measured. <b><i>Results:</i></b> CKD patients had fluid overload (FO) when compared to HC (overhydration index: CKD = 0.5 ± 1.9 L vs. HC = –0.5 ± 1.0 L; <i>p</i> = 0.03). MR-derived tissue sodium concentrations were predominantly higher in the subcutaneous (SC) compartment (median [interquartile range] CKD = 22.4 mmol/L [19.4–31.3] vs. HC = 18.4 mmol/L [16.6–21.3]; <i>p</i> = 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; <i>p</i> = 0.26). Tissue sodium in both compartments correlated to FO (muscle: <i>r</i> = 0.63, <i>p</i> &lt; 0.01; SC: <i>r</i>_s = 0.63, <i>p</i> &lt; 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (<i>p</i> &lt; 0.05), tumor necrosis factor-alpha (<i>p</i> &lt; 0.01), and interleukin (IL)-6 (<i>p</i> = 0.01) and lower levels of vascular endothelial growth factor-C (<i>p</i> = 0.04). FO in CKD was linked to higher IL-8 (<i>r</i> = 0.51, <i>p</i> &lt; 0.05) and inversely associated to E-selectin (<i>r</i> = –0.52, <i>p</i> = 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; <i>r</i>_s = 0.54, <i>p</i> = 0.02). <b><i>Conclusion:</i></b> Salt and water accumulation in CKD appears to be linked with inflammation and endothelial activation pathways. Specifically IL-8, E-Selectin (in FO), and ICAM (in salt accumulation) may be implicated in the pathophysiology of FO and merit further investigation.