Extracellular overhydration linked with endothelial dysfunction in the context of inflammation in haemodialysis dependent chronic kidney disease

PLoS One. 2017 Aug 22;12(8):e0183281. doi: 10.1371/journal.pone.0183281. eCollection 2017.

Abstract

Background: Haemodialysis (HD) patients are predisposed to dysregulated fluid balance leading to extracellular water (ECW) expansion. Fluid overload has been closely linked with outcome in these patients. This has mainly been attributed to cardiac volume overload, but the relation between abnormalities in fluid status with micro- and macrovascular dysfunction has not been studied in detail. We studied the interaction of macro- and microvascular factors in states of normal and over- hydration in HD-dependent CKD.

Methods: Fluid compartments [total body water (TBW) and ECW] and overhydration index (OH) were measured with Multifrequency bio-impedance (BCM). Overhydration was defined as OH/ECW>7%. Overhydration was also assessed using the ECW/TBW ratio. Macrocirculation was assessed by pulse-wave velocity (PWV) and mean arterial pressure (MAP) measurements while microcirculation through sublingual capillaroscopy assessment of the Perfused Boundary Region of the endothelial glycocalyx (PBR 5-25mcg). A panel of pro-inflammatory and vascular serum biomarkers and growth factors was analysed.

Results: Of 72 HD participants, 30 were in normohydration (N) range and 42 overhydrated according to the OH/ECW ratio. Average ECW/TBW was 0.48±0.03. Overhydrated patients had higher MAP (122.9±22.5 v 111.7±22.2mmHg, p = 0.04) and comorbidities (median Davies score 1.5 v 1.0, p = 0.03). PWV (p = 0.25) and PBR 5-25mcg (p = 0.97) did not differ between the 2 groups. However, Vascular Adhesion Molecule (VCAM)-1, Interleukin-6 and Thrombomodulin, and reduced Leptin were observed in the overhydrated group. Elevation in VCAM-1 levels (OR 1.03; 95% CI 1.01-1.06; p = 0.02) showed a strong independent association with OH/ECW>7% in an adjusted logistic regression analysis and exhibited a strong linear relationship with ECW/TBW (Bata = 0.210, p = 0.03) in an also adjusted model.

Conclusion: Extracellular fluid overload is significantly linked to microinflammation and markers of endothelial dysfunction. The study provides novel insight in the cardiovascular risk profile associated with overhydration in uraemia.

MeSH terms

  • Adult
  • Aged
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Inflammation / etiology*
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Renal Dialysis* / adverse effects
  • Water-Electrolyte Balance*

Grants and funding

Funding for the INTHEMO study was secured through grants from the Dutch Kidney Foundation grant (SB 166; Grant recipient: Dr T Cornelis) and the Clinical Evidence Council of High Dose Hemodialysis, Baxter International (11CECHHDEU1004; Grant recipient: Dr T Cornelis). The research reported in this publication was supported by the National Institute for Health Research (NIHR) Devices for Dignity Healthcare Technology Co-operative and was supported by the NIHR Clinical Research Network (CRN) (NIHR UK CRN ID: 17528). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The above funding and supporting institutions had no role in the study design data collection and analysis, decision to publish or preparation of the manuscript.