title: Impaired vascular function contributes to exercise intolerance in chronic kidney disease.
abstract: Exercise intolerance is an important feature in patients with chronic kidney disease (CKD) and is prognostic for both increased morbidity and mortality. Little is known about the underlying mechanisms in predialysis CKD. This study aimed to gain more insight into the role of vascular dysfunction in the exercise intolerance of predialysis CKD. In addition, vascular-related microRNAs (miRNAs)-as epigenetic regulators of exercise capacity-were analysed.
  
  
  
  Sixty-three patients with CKD stages 1-5 and 18 healthy controls were included. Peak oxygen consumption (VO2peak) was determined by cardiopulmonary exercise testing, endothelial function by flow-mediated dilation (FMD) and arterial stiffness by carotid-femoral pulse wave velocity (PWV). Plasma miRNA levels (miR-21, miR-126, miR-146a, miR-150 and miR-210) were quantified by quantitative RT-PCR.
  
  
  
  VO2peak was already impaired in mild CKD (stages 1-3A) and significantly correlated with estimated glomerular filtration rate (eGFR; r = 0.525, P < 0.001). Likewise, both FMD and PWV were significantly correlated with eGFR (r = 0.319, P = 0.007 and r = -0.365, P = 0.001, respectively). In multiple regression analysis, PWV remained one of the strongest independent determinants of VO2peak (β = -0.301, P = 0.01). Of the studied miRNA, circulating levels of miR-146a and miR-150 correlated with eGFR, PWV and VO2peak, but the association with the latter was lost when correcting for PWV.
  
  
  
  Arterial stiffness contributes to the observed reduced aerobic capacity in predialysis CKD, independent of age, haemoglobin levels and endothelial function and represents a promising therapeutic target for improving exercise capacity in this population. Future work is required to elucidate why higher circulating levels of miR-146a and miR-150 are associated with impaired renal function and increased arterial stiffness.
authors.affiliation: Department of Nephrology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium.|Laboratory for Molecular and Cellular Cardiology, University of Antwerp, Edegem, Belgium.|Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Edegem, Belgium.
authors.forename: Amaryllis H
authors.initials: AH
authors.lastname: Van Craenenbroeck
authors.affiliation: Laboratory for Molecular and Cellular Cardiology, University of Antwerp, Edegem, Belgium.|Department of Cardiology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Emeline M
authors.initials: EM
authors.lastname: Van Craenenbroeck
authors.affiliation: Laboratory for Molecular and Cellular Cardiology, University of Antwerp, Edegem, Belgium.
authors.forename: Katrijn
authors.initials: K
authors.lastname: Van Ackeren
authors.affiliation: Laboratory for Molecular and Cellular Cardiology, University of Antwerp, Edegem, Belgium.
authors.forename: Vicky Y
authors.initials: VY
authors.lastname: Hoymans
authors.affiliation: Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Edegem, Belgium.
authors.forename: Gert A
authors.initials: GA
authors.lastname: Verpooten
authors.affiliation: Laboratory for Molecular and Cellular Cardiology, University of Antwerp, Edegem, Belgium.|Department of Cardiology, Antwerp University Hospital, Edegem, Belgium.
authors.forename: Christiaan J
authors.initials: CJ
authors.lastname: Vrints
authors.affiliation: Department of Nephrology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Edegem, Belgium.
authors.forename: Marie M
authors.initials: MM
authors.lastname: Couttenye
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood; D008875:Middle Aged; D010101:Oxygen Consumption; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D010807:Physical Endurance; D005082:Physical Exertion; D063177:Pulse Wave Analysis; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D059289:Vascular Stiffness; D014664:Vasodilation
chemical_list: D035683:MicroRNAs
keywords: arterial stiffness; chronic kidney disease; endothelial dysfunction; exercise intolerance; microRNA