Nicos Mitsides1,2,3, Fahad Mohammaed S Alsehli4, Damien Mc Hough5, Liliana Shalamanova4, Fiona Wilkinson4, Jane Alderdice6, Roshni Mitra7, Agnieszka Swiecicka8, Paul Brenchley9,10, Geoffrey J M Parker5,11, M Yvonne Alexander4, Sandip Mitra9,12,10. 1. Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom, nicos.mitsides3@srft.nhs.uk. 2. Department of Nephrology, Salford Royal NHS Foundation Trust, Salford, United Kingdom, nicos.mitsides3@srft.nhs.uk. 3. NIHR Devices for Dignity Healthcare Technology Co-Operative, Royal Hallamshire Hospital, Sheffield, United Kingdom, nicos.mitsides3@srft.nhs.uk. 4. Healthcare Science Research Institute, Manchester Metropolitan University, Manchester, United Kingdom. 5. Quantitative Biomedical Image Laboratory, Faculty of Biology, Medicine and Healthy, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom. 6. Department of Dietetics, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom. 7. Faculty of Medicine, Imperial College, London, United Kingdom. 8. Andrology Research Unit, Division of Gastroenterology, Endocrinology and Diabetes, Faculty of Biology, Medicine and Healthy, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom. 9. Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom. 10. Department of Nephrology, Central Manchester University Hospital NHS Foundation Trust, Manchester Academic Health Science Centre, and NIHR Devices for Dignity, Manchester, United Kingdom. 11. Bioxydyn Limited, Manchester, United Kingdom. 12. NIHR Devices for Dignity Healthcare Technology Co-Operative, Royal Hallamshire Hospital, Sheffield, United Kingdom.
Abstract
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.
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.
Authors: Anke Dahlmann; Peter Linz; Isabelle Zucker; Viktor Haag; Jonathan Jantsch; Thomas Dienemann; Armin M Nagel; Patrick Neubert; Daniela Rosenhauer; Manfred Rauh; Stephan Horn; Dominik N Müller; Mario Schiffer; Friedrich C Luft; Michael Uder; Christoph Kopp Journal: Kidney Int Rep Date: 2021-06-28