Effects of respiratory muscle training on endothelium and oxidative stress biomarkers in hemodialysis patients: a randomized clinical trial

Abstract

Introduction: Hemodialysis (HD) patients have altered pulmonary function and this is associated with impaired endothelial function and cardiovascular events. Respiratory muscle training (RMT) has the potential to improve cardiovascular outcomes in patients undergoing maintenance HD. Here, we evaluated the e ff ects of RMT on endothelium/glycocalyx, oxidative stress biomarkers and pulmonary function test in HD patients. Methods: This is a randomized controlled clinical trial including 41 patients undergoing thrice-weekly main- tenance HD. Patients were randomly assigned at a 2:1 ratio to receive or not RMT during HD sessions for 8 weeks. Main outcomes were changes in levels of the biomarkers related to endothelium activation (vascular cell adhesion molecule 1, VCAM-1, and intercellular adhesion molecule 1, ICAM-1), glycocalyx derangement (syn- decan-1), aberrant angiogenesis (angiopoietin-2) and oxidative stress (malondialdehyde) compared to baseline. Also, maximal inspiratory/expiratory pressure (MIP, MEP), Forced vital capacity (FVC) and forced expiratory volume in the fi rst second (FEV1) were evaluated. Other outcomes included changes in functional capacity and pulmonary function test. We also performed a post-hoc analysis of plasma endothelin-1 levels. Results: Of 56 randomly assigned patients, 41 were included in the primary fi nal analyses. RMT increased all pulmonary function parameters evaluated and signi fi cantly reduced plasma syndecan-1 levels at 8 weeks compared to placebo (between-group di ff erence: − 84.5; 95% CI, − 148.1 to − 20.9). Also, there was a reduction in plasma levels of angiopoietin-2 (between-group di ff erence: − 0.48; 95% CI, − 1.03 to − 0.097). Moreover, there was a signi fi cant reduction in mean blood pressure at rest (between-group di ff erence: − 12.2; 95%CI, − 17.8 to − 6.6) associated with a reduction in endothelin-1 levels (between-group di ff erence: − 0.164; 95% CI, − 0.293 to − 0.034). There was no di ff erence regarding biomarkers of endothelial activation or oxidative stress. Conclusion: A short-term RMT program ameliorate FVC, FEV1 and reduces syndecan-1 and angiopoietin-2 biomarker levels. Finally, better blood pressure control was attained during training and it was associated with a reduction in endothelin-1 levels.