Evaluation of Continuous Positive Airway Pressure Therapy on Renin-Angiotensin System Activity in Obstructive Sleep Apnea

摘要

Rationale: Obstructive sleep apnea (OSA) has been associated with kidney function loss, which may be related to changes in the renin-angiotensin system (RAS). Objectives: We sought to determine the effect of continuous positive airway pressure (CPAP) of patients with OSA on renal hemodynamics at baseline and in response to angiotensin Ⅱ (AngⅡ), which reflects RAS activity. Methods: Twenty normotensive, nondiabetic, newly diagnosed OSA subjects (15 men, 5 women, 50 ± 2 yr, respiratory disturbance index [RDI] ＞ 15 h~(-1)) with nocturnal hypoxemia (Sa_(O_2) ＜ 90% for ＞12% of the night) were studied in high-salt balance pre- and post-CPAP therapy (＞4 h CPAP useight for 1 mo). Glomerular filtration rate (GFR), renal plasma flow (RPF), and filtration fraction (FF) (a surrogate marker for intraglomerular pressure) were measured pre-and post-CPAP using inulin and para-aminohippurate clearance techniques at baseline and in response to graded AngⅡ infusion (3 ng/kg/min × 30 min and 6 ng/kg/min × 30 min, respectively). Measurements and Main Results: CPAP corrected OSA and hypoxemia (RDI: 42 ± 4 vs. 4 ± 1 h~(-1), P ＜ 0.001; duration Sa_(O_2) ＜ 90%: 36% ± 5% vs. 6 ± 2%, P ＜ 0.001). CPAP reduced GFR (124 ± 8 ml/min vs. 110 ± 6 ml/min, P = 0.014), increased RPF (692 ± 36 ml/min vs. 749 ± 40 ml/min, P = 0.059), and reduced baseline FF (18.9 ± 1.6% vs. 15.3 ± 1.0%, P = 0.004). Post-CPAP demonstrated a blunted GFR response (-9 ± 3 ml/min vs. -2 ± 2 ml/min, P = 0.033) and augmented RPF response (-182 ± 22 ml/min vs. -219 ± 25 ml/min, P = 0.024) to Angll. FF response was maintained (P = 0.4). CPAP reduced baseline mean arterial pressure (94 ± 2 vs. 89 ± 2 mm Hg, P = 0.002), plasma aldosterone (149 ± 18 vs. 109 ± 10 pmol/L, P = 0.003), and urinary protein excretion (61 [39-341] mg/day vs. 56 [22-204] mg/d, P = 0.003). Conclusions: CPAP therapy was associated with improved renal hemodynamics and down-regulation of renal RAS activity, suggesting a potential therapeutic benefit for kidney function.