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

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 (5-25μm) 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.

• Authors: 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
• Journal: Kidney & blood pressure research (Kidney Blood Press Res) Vol. 42 Issue 5 Pg. 905-918 ( 2017) ISSN: 1423-0143 [Electronic] Switzerland
• PMID: 29145197 (Publication Type: Journal Article, Multicenter Study)
• Copyright: © 2017 The Author(s). Published by S. Karger AG, Basel.

Chemical References

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

Topics

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