Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease

Nicos Mitsides, Fahad Mohammaed S Alsehli, Damien Mc Hough, Liliana Shalamanova, Fiona Wilkinson, Jane Alderdice, Roshni Mitra, Agnieszka Swiecicka, Paul Brenchley, Geoffrey J M Parker, M Yvonne Alexander, Sandip Mitra

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Progressive chronic kidney disease (CKD) inevitably leads to salt and water retention and disturbances in the macro-and microcirculation.

OBJECTIVES: We hypothesize that salt and water dysregulation in advanced CKD may be linked to inflammation and microvascular injury pathways.

METHODS: 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.

RESULTS: 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; p = 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]; p = 0.03), but not the muscle (CKD = 24.9 ± 5.5 mmol/L vs. HC = 22.8 ± 2.5 mmol/L; p = 0.26). Tissue sodium in both compartments correlated to FO (muscle: r = 0.63, p < 0.01; SC: rs = 0.63, p < 0.01). CKD subjects had elevated levels of vascular cell adhesion molecule (p < 0.05), tumor necrosis factor-alpha (p < 0.01), and interleukin (IL)-6 (p = 0.01) and lower levels of vascular endothelial growth factor-C (p = 0.04). FO in CKD was linked to higher IL-8 (r = 0.51, p < 0.05) and inversely associated to E-selectin (r = -0.52, p = 0.01). Higher SC sodium was linked to higher intracellular adhesion molecule (ICAM; rs = 0.54, p = 0.02).

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalThe Nephron Journals
Early online date12 Sept 2019
Publication statusPublished - 2019


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