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

Kidney Blood Press Res. 2017;42(5):905-918. doi: 10.1159/000485048. Epub 2017 Nov 16.


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 (5-25μm) 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.

Keywords: Endothelium; Hemodialysis; IL-8; TNF-α.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inducing Agents*
  • Humans
  • Inflammation*
  • Interleukin-8 / metabolism
  • Kidney Failure, Chronic / therapy*
  • Microvessels / drug effects
  • Microvessels / injuries*
  • Microvessels / pathology
  • Middle Aged
  • Renal Dialysis / methods*
  • Vascular Endothelial Growth Factor Receptor-1 / physiology


  • Angiogenesis Inducing Agents
  • CXCL8 protein, human
  • Interleukin-8
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1