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Sex differences in renal hemodynamics and renin-angiotensin system activity post-CPAP therapy in humans with
David D M Nicholl1, Patrick J Hanly2,3,4, Ann A Zalucky5
1Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Abstract:
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.
Insights
Continuous positive airway pressure (CPAP) therapy improved renal hemodynamics in both men and women with obstructive sleep apnea (OSA). CPAP also downregulated renal renin-angiotensin system (RAS) activity in women, but not in men.
Area of Science:
- Nephrology
- Cardiovascular Physiology
- Sleep Medicine
Background:
- Men exhibit accelerated kidney function decline and heightened renal renin-angiotensin system (RAS) activity compared to women.
- Obstructive sleep apnea (OSA) is prevalent in chronic kidney disease, with sex-specific vascular effects and potential for CPAP therapy to reverse glomerular hyperfiltration.
- Understanding sex differences in CPAP's impact on renal hemodynamics and RAS is crucial for targeted OSA management in kidney disease.
Purpose of the Study:
- To investigate the sex-specific effects of continuous positive airway pressure (CPAP) on renal hemodynamics and the renal renin-angiotensin system (RAS) in patients with obstructive sleep apnea (OSA).
Main Methods:
- Twenty-nine participants with OSA (10 women, 19 men) underwent assessment of renal hemodynamics (RPF, GFR, FF) and response to ANG II challenge before and after 4 weeks of nightly CPAP therapy.
- Renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction (FF) were measured.
- Renal RAS activity was assessed via response to angiotensin II (ANG II) challenge.
Main Results:
- In women, CPAP increased RPF, maintained GFR, and reduced FF. In men, CPAP maintained RPF and GFR, and reduced FF.
- Pre-CPAP, no sex differences in renal hemodynamic responses to ANG II were observed.
- CPAP enhanced the renovasoconstrictive response to ANG II in women but not men, suggesting downregulated renal RAS activity in women post-CPAP.
Conclusions:
- CPAP therapy improves renal hemodynamics in both sexes with OSA.
- CPAP downregulates renal RAS activity in women with OSA, but not in men.
- These findings highlight sex-specific responses to CPAP in the context of OSA and kidney health.
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