TY - JOUR
T1 - Salt and Water Retention Is Associated with Microinflammation and Endothelial Injury in Chronic Kidney Disease
AU - Mitsides, Nicos
AU - Alsehli, Fahad Mohammaed S.
AU - Mc Hough, Damien
AU - Shalamanova, Liliana
AU - Wilkinson, Fiona
AU - Alderdice, Jane
AU - Mitra, Roshni
AU - Swiecicka, Agnieszka
AU - Brenchley, Paul
AU - Parker, Geoffrey J.M.
AU - Alexander, M. Yvonne
AU - Mitra, Sandip
N1 - Funding Information:
We would also like to thank the clinical and technical staff at the participating units, the Manchester Renal Research and Transplant Laboratory and the Welcome Trust Manchester Imaging Facilities for their help and support. The research reported in this publication was supported by the Cancer Research UK and Engineering and Physical Science Research Council Cancer Image Centre in Cambridge and Manchester and the National Institute for Health Research Devices for Dignity Medtech Co-operative. The views expressed are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.
Funding Information:
The study received grant funding from Kidneys for Life, and the University of Manchester MR Imaging Facilities Grant. None of the above funding bodies had any role in the design of the study, analysis of the data of preparation of this manuscript.
Publisher Copyright:
© 2019 S. Karger AG, Basel. Copyright: All rights reserved.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Chronic kidney disease
KW - Inflammation
KW - Overhydration
UR - http://www.scopus.com/inward/record.url?scp=85072282149&partnerID=8YFLogxK
U2 - 10.1159/000502011
DO - 10.1159/000502011
M3 - Article
C2 - 31514183
AN - SCOPUS:85072282149
SN - 1660-8151
VL - 143
SP - 234
EP - 242
JO - Nephron
JF - Nephron
IS - 4
ER -