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

Abstract

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 ≥ 15 h−1) with NH (SpO2 < 90% ≥ 12%/night) were studied pre- and post-CPAP (>4 h/night∙4 weeks). 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 (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 (Δ30 min, −9 ± 4 vs 1 ± 3 mL/min, p = 0.021; Δ60 min, −5 ± 5 vs 8 ± 5 mL/min, p = 0.017) and RPF (Δ30 min, −165 ± 13 vs −93 ± 19 mL/min, p = 0.003; Δ60 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 (Δ30 min, −93 ± 19 vs −138 ± 16 mL/min, p = 0.009; Δ60 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.