Nocturnal Hypoxemia Severity and Renin–Angiotensin System Activity in Obstructive Sleep Apnea

Men have faster loss of kidney function and greater renal renin-angiotensin system (RAS) activity compared with women. Obstructive sleep apnea (OSA) is common in chronic kidney disease; the vascular effects of OSA differ by sex, and OSA-associated glomerular hyperfiltration can be reversed by continuous positive airway pressure (CPAP) therapy. We evaluated sex differences in the effect of CPAP on renal hemodynamics and the renal RAS in OSA. Twenty-nine Na+-replete, otherwise healthy study participants with OSA (10 women and 19 men) with nocturnal hypoxemia were studied pre- and post-CPAP (>4 h/night for 4 wk). Renal hemodynamics [renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction(FF)] were measured at baseline and in response to ANG II challenge, as a marker of renal RAS activity, pre- and post-CPAP therapy for 1 mo. In women, CPAP was associated with increased RPF (626 ± 22 vs. 718 ± 43 mL/min, P = 0.007, pre- vs. post-CPAP), maintained GFR (108 ± 2 vs. 105 ± 3 mL/min, P = 0.8), and reduced FF (17.4 ± 0.8% vs. 15.0 ± 0.7%, P = 0.017). In men, CPAP was associated with maintained RPF (710 ± 37 vs. 756 ± 38 mL/min, P = 0.1), maintained GFR (124 ± 8 vs. 113 ± 6 mL/min, P = 0.055), and reduced FF (18.6 ± 1.7% vs. 15.5 ± 1.1%, P = 0.035). Pre-CPAP, there were no sex differences in renal hemodynamic responses to ANG II. CPAP use was associated with a greater renovasoconstrictive response to ANG II in women (RPF at Δ30 min: −100 ± 27 vs. −161 ± 25 mL/min, P = 0.007, and RPF at Δ60 min: −138 ± 27 vs. −206 ± 32 mL/min, P = 0.007) but not men. CPAP use was associated with improved renal hemodynamics in both sexes and downregulated renal RAS activity in women but not men.

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Evaluation of Continuous Positive Airway Pressure Therapy on Renin–Angiotensin System Activity in Obstructive Sleep Apnea

American Journal of Respiratory and Critical Care Medicine ◽

10.1164/rccm.201403-0526oc ◽

2014 ◽

Vol 190 (5) ◽

pp. 572-580 ◽

Cited By ~ 58

Author(s):

David D. M. Nicholl ◽

Patrick J. Hanly ◽

Marc J. Poulin ◽

George B. Handley ◽

Brenda R. Hemmelgarn ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Continuous Positive Airway Pressure ◽

Airway Pressure ◽

Positive Airway Pressure ◽

Renin Angiotensin System ◽

Pressure Therapy ◽

Angiotensin System ◽

System Activity ◽

Obstructive Sleep

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Obstructive Sleep Apnea And The Vascular Renin Angiotensin System In Humans

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a2185 ◽

2012 ◽

Author(s):

David D.M. Nicholl ◽

Patrick Hanly ◽

George Handley ◽

Brenda Hemmelgarn ◽

Marc Poulin ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Renin Angiotensin System ◽

Angiotensin System ◽

Renin Angiotensin ◽

Obstructive Sleep

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Nocturnal hypoxemia severity influences the effect of CPAP therapy on renal renin-angiotensin-aldosterone system activity in humans with obstructive sleep apnea

SLEEP ◽

10.1093/sleep/zsaa228 ◽

2020 ◽

Author(s):

David D M Nicholl ◽

Patrick J Hanly ◽

Ann A Zalucky ◽

George B Handley ◽

Darlene Y Sola ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Angiotensin Ii ◽

Renal Hemodynamics ◽

Cpap Therapy ◽

Renin Angiotensin Aldosterone System ◽

Renin Angiotensin ◽

Nocturnal Hypoxemia ◽

Obstructive Sleep ◽

The Impact

Abstract Study Objectives Nocturnal hypoxemia (NH) in obstructive sleep apnea (OSA) is associated with renal renin-angiotensin-aldosterone system (RAAS) up-regulation and loss of kidney function. Continuous positive airway pressure (CPAP) therapy is associated with RAAS down-regulation, though the impact of NH severity remains unknown. We sought to determine whether NH severity alters the effect of CPAP on renal hemodynamics and RAAS activity in humans. Methods Thirty sodium-replete, otherwise healthy, OSA participants (oxygen desaturation index ≥15h -1) with NH (SpO2<90%≥12%/night) were studied pre- and post-CPAP (>4h/night∙4wks). NH severity was characterized as moderate (mean SpO2[MSpO2]≥90%; N=15) or severe (MSpO2<90%; N=15). Glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF) were measured at baseline and in response to Angiotensin-II (3ng/kg/min∙30min, 6ng/kg/min∙30min), a marker of RAAS activity. Results Pre-CPAP, baseline renal hemodynamics did not differ by NH severity. Pre-CPAP, severe NH participants demonstrated blunted GFR (Δ30min, -9±4 vs 1±3mL/min, p=0.021; Δ60min, -5±5 vs 8±5mL/min, p=0.017) and RPF (Δ30min, -165±13 vs -93±19mL/min, p=0.003; Δ60min, -208±18 vs -112±22mL/min, p=0.001; moderate vs severe) responses to Angiotensin-II. Post-CPAP, severe NH participants demonstrated maintained GFR (112±5 vs 108±3mL/min, p=0.9), increased RPF (664±35 vs 745±34mL/min, p=0.009), reduced FF (17.6±1.4 vs 14.9±0.6%, p=0.009), and augmented RPF responses to Angiotensin-II (Δ30min, -93±19 vs -138±16mL/min, p=0.009; Δ60min, -112±22 vs -175±20mL/min, p=0.001; pre- vs post-CPAP), while moderate participants were unchanged. Conclusions Correction of severe, but not moderate, NH with CPAP therapy was associated with improved renal hemodynamics and decreased renal RAAS activity in humans with OSA.

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