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.