Nocturnal Hypoxemia Severity Influences The Effect Of Cpap Therapy On Renal Renin-Angiotensin-Aldosterone System Activity In Humans With Obstructive Sleep Apnea

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 z >= 15 h(-1)) with NH (SpO(2) < 90% >= 12%/night) were studied pre- and post-CPAP (>4 h/night-4 weeks). NH severity was characterized as moderate (mean SpO(2)[MSpO(2)] >= 90%; N =15) or severe (MSpO(2 )< 90%; N = 15). Glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF) were measured at baseline and in response to angiotensin-Il (3 ng/kg/min.30 min, 6 ng/kg/min.30 min), 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 (Delta 30 min, -9 +/- 4 vs 1 +/- 3 mL/min, p = 0.021; Delta 60 min, -5 +/- 5 vs 8 +/- 5 mL/min, p = 0.017) and RPF (Delta 30 min, -165 +/- 13 vs -93 +/- 19 mL/min, p = 0.003; Delta 60 min, -208 +/- 18 vs -112 +/- 22 mL/min, p = 0.001; moderate vs severe) responses to angiotensin-II. Post-CPAP, severe NH participants demonstrated maintained GFR (112 +/- 5 vs 108 +/- 3 mL/min, p = 0.9), increased RPF (664 +/- 35 vs 745 +/- 34 mL/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 (Delta 30 min, -93 +/- 19 vs -138 +/- 16 mL/min, p = 0.009; Delta 60 min, -112 +/- 22 vs -175 +/- 20 mL/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.