Inflammatory and Angiogenic Factors Linked to Longitudinal Microvascular Changes in Hemodialysis Patients Irrespective of Treatment Dose Intensity

Nicos Mitsides*, Tom Cornelis, Natascha J. H. Broers, Nanada M. P. Diederen, Paul Brenchley, Nicole Heitink-ter Braak, Frank M. van der Sande, Casper G. Schalkwijk, Jeroen P. Kooman, Sandip Mitra

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Cardiovascular disease is a major contributor to the poor outcomes observed in hemodialysis. We investigated the relationship between hemodialysis intensity and vascular parameters in high-dose (HDHD; > 12hrs/week) and Conventional (CHD; = 12hrs/week) hemodialysis intensity over a 6-month period. Methods: We present the 6-month longitudinal analysis of a 2-year multicenter study investigating the effects of HDHD on cardiovascular parameters. We used pulse wave velocity, 24hr ambulatory blood pressure and sublingual dark field capillaroscopy measurements to assess macro-and microcirculation on 6-monthly basis. Pro-inflammatory and endothelial biomarkers were also measured at 6-monthly intervals. Results: 47 participants (21 HDHD, 26 CHD) were studied. CHD were older (63.5 +/- 14.2 vs 53.7 +/- 12.6 yr; p = 0.018), with shorter dialysis vintage (median 23 vs 61 months; p = 0.001). There was considerable variability in the degree and direction of change of circulatory measurements over a 6-month period. Hemodialysis intensity (hrs/week) did not correlate to these changes, when adjusted for age, dialysis vintage and comorbidity. Higher levels of Interleukin (IL)-8 measured at baseline independently predicted an increase in the Perfused Boundary Region (5-25 mu m) of the endothelial glycocalyx (p=0.010) whilst higher levels of soluble Flt-1 had a significant inverse effect (p=0.002) in an adjusted linear model. Conclusion: Hemodialysis intensity did not predict changes in either macro-or microvascular parameters. Inflammation mediated through the IL-8 pathway predicted microvascular injury while Flt-1, a potential marker of angiogenesis and endothelial repair, might have a significant protective role. Further understanding of these pathways will be necessary to improve dialysis outcomes. (C) 2017 The Author(s) Published by S. Karger AG, Basel

Original languageEnglish
Pages (from-to)905-918
Number of pages14
JournalKidney & Blood Pressure Research
Volume43
Issue number5
DOIs
Publication statusPublished - 2017

Keywords

  • Hemodialysis
  • Endothelium
  • IL-8
  • TNF-alpha
  • CHRONIC KIDNEY-DISEASE
  • C-REACTIVE PROTEIN
  • PERITONEAL-DIALYSIS PATIENTS
  • RANDOMIZED-CONTROLLED-TRIAL
  • NECROSIS-FACTOR-ALPHA
  • TYROSINE KINASE 1
  • CARDIOVASCULAR RISK
  • ARTERIAL STIFFNESS
  • CONVENTIONAL HEMODIALYSIS
  • ENDOTHELIAL GLYCOCALYX

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