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

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(O2) < 90% for >12% of the night) were studied in high-salt balance pre- and post-CPAP therapy (>4 h CPAP use/night 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 X 30 min and 6 ng/kg/min X 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(O2) < 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 AngII. 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 = 0003), 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.