title: Nocturnal hypoxemia severity and renin-angiotensin system activity in obstructive sleep apnea.
abstract: BACKGROUND
  Obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with chronic kidney disease and up-regulation of the renin-angiotensin system (RAS), which is deleterious to renal function. The extent to which the magnitude of RAS activation is influenced by the severity of nocturnal hypoxemia and comorbid obesity has not been determined.
  
  
  OBJECTIVE
  To determine the association between the severity of nocturnal hypoxemia and RAS activity and whether this is independent of obesity in patients with OSA.
  
  
  METHODS
  Effective renal plasma flow (ERPF) response to angiotensin II (AngII) challenge, a marker of renal RAS activity, was measured by paraaminohippurate clearance technique in 31 OSA subjects (respiratory disturbance index, 51 ± 25 h(-1)), stratified according to nocturnal hypoxemia status (mean nocturnal SaO2, ≥90% [moderate hypoxemia] or <90% [severe hypoxemia]) and 13 obese control subjects.
  
  
  RESULTS
  Compared with control subjects, OSA subjects demonstrated decreased renovascular sensitivity (ERPF, -153 ± 79 vs. -283 ± 31 ml/min; P = 0.004) (filtration fraction, 5.4 ± 3.8 vs. 7.1 ± 2.6%; P = 0.0025) in response to 60 minutes of AngII challenge (mean ± SD; all P values OSA vs. control). The fall in ERPF in response to AngII was less in patients with severe hypoxemia compared with those with moderate hypoxemia (P = 0.001) and obese control subjects after 30 minutes (P < 0.001) and 60 minutes (P < 0.001) of AngII challenge, reflecting more augmented renal RAS activity. Severity of hypoxemia was not associated with the blood pressure or the systemic circulating RAS component response to AngII.
  
  
  CONCLUSIONS
  The severity of nocturnal hypoxemia influences the magnitude of renal, but not the systemic, RAS activation independently of obesity in patients with OSA.
authors.affiliation: 1 Department of Medicine.
authors.forename: Ann A
authors.initials: AA
authors.lastname: Zalucky
authors.affiliation: 1 Department of Medicine.
authors.forename: David D M
authors.initials: DD
authors.lastname: Nicholl
authors.affiliation: 1 Department of Medicine.|2 Sleep Centre, Foothills Medical Centre, Calgary, Alberta, Canada.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanly
authors.affiliation: 4 Department of Physiology and Pharmacology.|5 Department of Clinical Neurosciences.|6 Hotchkiss Brain Institute.|7 Faculty of Kinesiology, and.|3 Libin Cardiovascular Institute of Alberta, Calgary, Alberta, Canada.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Poulin
authors.affiliation: 9 Department of Family Medicine, University of Calgary, Calgary, Alberta, Canada.|8 Alberta Kidney Disease Network, Calgary, Alberta, Canada.
authors.forename: Tanvir C
authors.initials: TC
authors.lastname: Turin
authors.affiliation: 9 Department of Family Medicine, University of Calgary, Calgary, Alberta, Canada.|10 Calgary Weight Management Centre, Calgary, Alberta, Canada; and.
authors.forename: Shahebina
authors.initials: S
authors.lastname: Walji
authors.affiliation: 11 Healthy Heart Sleep Company, Calgary, Alberta, Canada.
authors.forename: George B
authors.initials: GB
authors.lastname: Handley
authors.affiliation: 1 Department of Medicine.|2 Sleep Centre, Foothills Medical Centre, Calgary, Alberta, Canada.
authors.forename: Jill K
authors.initials: JK
authors.lastname: Raneri
authors.affiliation: 1 Department of Medicine.|3 Libin Cardiovascular Institute of Alberta, Calgary, Alberta, Canada.
authors.forename: Darlene Y
authors.initials: DY
authors.lastname: Sola
authors.affiliation: 1 Department of Medicine.|3 Libin Cardiovascular Institute of Alberta, Calgary, Alberta, Canada.|8 Alberta Kidney Disease Network, Calgary, Alberta, Canada.
authors.forename: Sofia B
authors.identifier: http://orcid.org/0000-0003-3000-2229
authors.initials: SB
authors.lastname: Ahmed
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015897:Comorbidity; D005260:Female; D006439:Hemodynamics; D006801:Humans; D000860:Hypoxia / Q000453:epidemiology / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology; D012039:Regional Blood Flow; D012084:Renin-Angiotensin System / Q000502:physiology*; D020181:Sleep Apnea, Obstructive / Q000453:epidemiology / Q000503:physiopathology*; D055815:Young Adult
keywords: angiotensin; hemodynamics; hypoxemia; kidney; obstructive sleep apnea