Intradialytic cycling does not exacerbate microparticles or circulating markers of systemic inflammation in haemodialysis patients

Abstract

Purpose: Patients receiving haemodialysis (HD) display elevated circulating microparticle (MP) concentration, tissue factor (TF) expression and markers of systemic inflammation, though regular intradialytic cycling (IDC) may have a therapeutic effect. This study investigated the impact of regular, moderate-intensity IDC on circulating MPs and inflammatory markers in unit-based HD patients.

Methods: Patients were cluster-randomised to intervention (n = 20, age: 51.4 ± 18.1 years, body mass: 77.6 ± 18.3 kg, mean ± SD) or no-exercise control (n = 20, 56.8 ± 14.0 years, 80.5 ± 26.5 kg). Intervention participants completed 30 min of moderate intensity (rating of perceived exertion [RPE] of 12-14) IDC, thrice weekly for 6 months. Pre-dialysis venous blood samples were obtained at 0, 3 and 6 months. Circulating MP phenotypes, cytokines, chemokine and MP TF expression were quantified using flow cytometry and cytometric bead array assays.

Results: Despite high exercise compliance (82%), no IDC-dependent effects were observed for any MP, cytokine or chemokine measure (p ≥ 0.051, η_ρ² ≤ 0.399) other than TNF-α (p = 0.001, η_ρ² = 0.186), though no significance was revealed upon post hoc analysis.

Conclusion: Six months of regular, moderate-intensity IDC had no effect on MPs, cytokines or chemokines. This suggests that the exercise did not exacerbate thrombotic or inflammatory status, though further functional assays are required to confirm this.

Trial registration: ISRCTN1129707, prospectively registered on 05/03/2015.

Keywords: Aerobic exercise; End-stage renal disease; Haemodialysis; Inflammation; Intradialytic cycling; Microparticles.

Fig. 1

MP flow cytometry gating strategy. A Mega-mix beads (BioCytex, Theale, UK, product reference 7801) of known size (0.5 µm, 0.9 µm, and 3.0 µm) to determine subsequent size gating. Two distinct populations (0.5 and 0.9 µm beads, shown in red) are visible, and thus the gate can be set to include these populations whilst excluding the 3.0 µm population (not visible here). B ‘All MPs’ based on size, set using previous mega-mix beads. The minimum trigger threshold of 0.3 µm is necessary to exclude the noise floor inherent in all cytometers, hence why the visible MP population (known to be comprised of particles ranging from 0.1 to 1.0 µm in diameter) is cut off at around 10⁴ on the X axis. C Phenotype marker expression (CD14, CD42b, CD66b, CD144—all four phenotypes employed the same gating strategy), used to quantify MPs of different cellular sources. D Tissue Factor expression, back-gated onto the previous graph (C) to identify those particles presenting as positive for both their phenotype marker and TF (CD142)

Fig. 2

Circulating concentration of neutrophil-derived MPs (NMP) (a), endothelial cell-derived MPs (EMP) (b) and the percentage of EMPs that express TF (c). Data are presented as ‘mean ± SD’. Concentration data were non-normally distributed and thus logarithmically transformed prior to analysis, whilst percentage data were normally distributed (control n = 20, exercise n = 20)

Fig. 3

Circulating IL-6 (a), IL-10 (b) and TNF-α (c) levels. Data are presented as ‘mean ± SD’. These data were non-normally distributed and thus logarithmically transformed prior to analysis (control n = 20, IDC exercise n = 20)