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

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.

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Sex differences in renal hemodynamics and renin-angiotensin system activity post-CPAP therapy in humans with obstructive sleep apnea

AJP Renal Physiology ◽

10.1152/ajprenal.00290.2019 ◽

2020 ◽

Vol 318 (1) ◽

pp. F25-F34 ◽

Cited By ~ 2

Author(s):

David D. M. Nicholl ◽

Patrick J. Hanly ◽

Ann A. Zalucky ◽

George B. Handley ◽

Darlene Y. Sola ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sex Differences ◽

Sleep Apnea ◽

Renin Angiotensin System ◽

Renal Hemodynamics ◽

Ang Ii ◽

Cpap Therapy ◽

Angiotensin System ◽

Renin Angiotensin ◽

Obstructive Sleep

Men have faster loss of kidney function and greater renal renin-angiotensin system (RAS) activity compared with women. Obstructive sleep apnea (OSA) is common in chronic kidney disease; the vascular effects of OSA differ by sex, and OSA-associated glomerular hyperfiltration can be reversed by continuous positive airway pressure (CPAP) therapy. We evaluated sex differences in the effect of CPAP on renal hemodynamics and the renal RAS in OSA. Twenty-nine Na+-replete, otherwise healthy study participants with OSA (10 women and 19 men) with nocturnal hypoxemia were studied pre- and post-CPAP (>4 h/night for 4 wk). Renal hemodynamics [renal plasma flow (RPF), glomerular filtration rate (GFR), and filtration fraction(FF)] were measured at baseline and in response to ANG II challenge, as a marker of renal RAS activity, pre- and post-CPAP therapy for 1 mo. In women, CPAP was associated with increased RPF (626 ± 22 vs. 718 ± 43 mL/min, P = 0.007, pre- vs. post-CPAP), maintained GFR (108 ± 2 vs. 105 ± 3 mL/min, P = 0.8), and reduced FF (17.4 ± 0.8% vs. 15.0 ± 0.7%, P = 0.017). In men, CPAP was associated with maintained RPF (710 ± 37 vs. 756 ± 38 mL/min, P = 0.1), maintained GFR (124 ± 8 vs. 113 ± 6 mL/min, P = 0.055), and reduced FF (18.6 ± 1.7% vs. 15.5 ± 1.1%, P = 0.035). Pre-CPAP, there were no sex differences in renal hemodynamic responses to ANG II. CPAP use was associated with a greater renovasoconstrictive response to ANG II in women (RPF at Δ30 min: −100 ± 27 vs. −161 ± 25 mL/min, P = 0.007, and RPF at Δ60 min: −138 ± 27 vs. −206 ± 32 mL/min, P = 0.007) but not men. CPAP use was associated with improved renal hemodynamics in both sexes and downregulated renal RAS activity in women but not men.

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Cardiovascular outcomes of CPAP therapy in obstructive sleep apnea syndrome

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00401.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. R1666-R1670 ◽

Cited By ~ 36

Author(s):

Walter T. McNicholas

Keyword(s):

Cardiovascular Disease ◽

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Obstructive Sleep Apnea Syndrome ◽

Sleep Apnea Syndrome ◽

Cpap Therapy ◽

Obstructive Sleep ◽

Cardiovascular Morbidity And Mortality ◽

Apnea Syndrome ◽

The Impact

Considerable evidence is now available of an independent association between obstructive sleep apnea syndrome (OSAS) and cardiovascular disease. The association is particularly strong for systemic arterial hypertension, but there is growing evidence of an association with ischemic heart disease and stroke. The mechanisms underlying cardiovascular disease in patients with OSAS are still poorly understood. However, the pathogenesis is likely to be a multifactorial process involving a diverse range of mechanisms, including sympathetic overactivity, selective activation of inflammatory molecular pathways, endothelial dysfunction, abnormal coagulation, and metabolic dysregulation, the latter particularly involving insulin resistance and disordered lipid metabolism. Therapy with continuous positive airway pressure (CPAP) has been associated with significant benefits to cardiovascular morbidity and mortality, both in short-term studies addressing specific aspects of morbidity, such as hypertension, and more recently in long-term studies that have evaluated major outcomes of cardiovascular morbidity and mortality. However, there is a clear need for further studies evaluating the impact of CPAP therapy on cardiovascular outcomes. Furthermore, studies on the impact of CPAP therapy have provided useful information concerning the role of basic cell and molecular mechanisms in the pathophysiology of OSAS.

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464 Long term effects of Continuous Positive Airway Pressure on the weight of Obstructive Sleep Apnea patients in the southeast USA

SLEEP ◽

10.1093/sleep/zsab072.463 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A183-A183

Author(s):

Carmel Joseph ◽

Noel Puthenveetil ◽

Allen Joe ◽

Jaya Therattil

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Weight Change ◽

Cpap Therapy ◽

Long Term Effects ◽

Weight Changes ◽

Southeast Usa ◽

Obstructive Sleep ◽

The Impact

Abstract Introduction Obesity has been linked to exacerbating Obstructive Sleep Apnea in patients. Paradoxically however, effective CPAP therapy has been noted to lead to weight increases even while improving hypersomnia and daytime neurocognitive functioning. Prior studies have demonstrated inconsistent results regarding weight changes while on CPAP therapy. Our study aims to clarify these inconsistencies and provide specific recommendations for CPAP compliant patients to prevent weight gain. Methods 393 OSA patients were seen for multiple follow ups since initiation of CPAP therapy at a single center sleep clinic. Every visit their weight would be updated along with CPAP compliance. Data was assessed on 1 month, 6 month, and 12 month intervals. Exclusion criteria include diuretic use, diet/exercise additions, and discontinuation of CPAP therapy before the full observation window. Results Patients with long term use of their CPAP devices had an average increase of 2.68±11.29 lbs after a year. 233 participants gained weight (an average of 9.8±7.3 lbs) while 141 participants lost weight (an average of -8.5±7.2 lbs) with 19 participants showing no weight change. This weight change could be observed starting as early as one month after CPAP initiation. Conclusion CPAP therapy is most likely linked to a lasting increase in weight. Recommendations and patient education for OSA patients should be modified to include an exercise component (10,000 steps/day) and/or caloric restriction (2200 low carb diet) to offset this weight increase. Further study is needed to assess the impact such recommendations could have in long term OSA care beyond the southeast USA. Support (if any) Pulmonary Allergy & Sleep Center of Augusta

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