Kidney Week

Abstract: TH-OR078

Sex Differences in the Renal Hemodynamic Response to Angiotensin II Post-CPAP Therapy in Women and Men with Obstructive Sleep Apnea

Session Information

• Hypertension and CVD: Basic Mechanisms
  October 25, 2018 | Location: 6F, San Diego Convention Center
  Abstract Time: 05:54 PM - 06:06 PM

Category: Hypertension and CVD

• 1403 Hypertension and CVD: Mechanisms

Authors

• Nicholl, David Donald McTavish, University of Calgary, Calgary, Alberta, Canada

David Donald McTavish Nicholl, MD

Completed MD, MSc, and Core Internal Medicine Residency at the University of Calgary in Calgary, AB, Canada Presently a PGY-4 Nephrology Fellow at Western University, in London, ON, Canada

• Hanly, Patrick, University of Calgary, Calgary, Alberta, Canada

Patrick Hanly,

• Zalucky, Ann A., University of Calgary, Calgary, Alberta, Canada

Ann A. Zalucky,

• Handley, George, Healthy Heart Sleep Company, Calgary, Alberta, Canada

George Handley,

• Sola, Darlene Y., University of Calgary, Calgary, Alberta, Canada

Darlene Y. Sola,

• Ahmed, Sofia B., University of Calgary, Calgary, Alberta, Canada

Sofia B. Ahmed,

Background

Women have slower loss of kidney function and chronic kidney disease (CKD) progression. The renin-angiotensin system (RAS) and the vascular effects of obstructive sleep apnea (OSA) differ by sex. OSA is associated with glomerular hypertension which can be reversed by continuous positive airway pressure (CPAP) therapy. We sought to determine whether sex differences exist in the effect of CPAP for OSA on renal hemodynamics and the renal RAS in humans.

Methods

Twenty-nine (10 female, 19 male; 49±2y) incident, otherwise healthy, OSA subjects (respiratory disturbance index [RDI]>15h^-1) with nocturnal hypoxemia (SaO₂<90% >12%/night) were studied in high-salt balance, a state of maximal RAS suppression, pre-CPAP and after 4 weeks of effective CPAP therapy (>4h/night). Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured by para-aminohippurate and inulin clearance technique at baseline and in response to Angiotensin II (AngII) challenge (3ng/kg/min x 30min, 6ng/kg/min x 30min), a marker of renal RAS activity, pre- and post-CPAP. The primary outcome was the effect of CPAP on the renal hemodynamic responses to AngII in women compared to men.

Results

CPAP corrected OSA and nocturnal hypoxemia (RDI: 44±4 vs 4±1hr^-1, p<0.001; duration SaO₂<90%: 45±6 vs 7±2%, p<0.001). In women, CPAP was associated with a significant increase in RPF (626±22 vs 718±43 mL/min, p=0.007) but no change in GFR (108±2 vs 105±3 mL/min, p=0.8), whereas in men, CPAP use was not associated with changes in renal hemodynamics (RPF: 710±37 vs 756±38 mL/min, p=0.11; p=0.7 vs women; GFR: 124±8 vs 113±6 mL/min, p=0.085; p=0.5 vs women). Pre-CPAP, there was no difference in the RPF or GFR responses to AngII between women and men. Post-CPAP, there was a significantly greater renovasoconstrictive response to AngII in women (RPF: Δ30min: -100±27 vs -161±25 mL/min, p=0.007; Δ60min: -138±27 vs -206±32 mL/min, p=0.007), but not in men (RPF: Δ30min: -142±14 vs -154±19 mL/min, p=0.4; Δ60min: -168±23 vs -200±23 mL/min, p=0.053). Post-CPAP women had a larger initial reduction in GFR in response to AngII compared to men (Δ30min: -5±3 vs 0±2 mL/min, p=0.039; vs men).

Conclusion

CPAP therapy for OSA is associated with altered renal hemodynamics and downregulation of renal RAS activity in women but not in men.