Nocturnal Hypoxemia Severity and Renin–Angiotensin System Activity in Obstructive Sleep Apnea

Zalucky, Ann A; Nicholl, David D M; Hanly, Patrick J.; Poulin, Marc J.; Turin, Tanvir Chowdhury; Walji, Shahebina; Handley, George B.; Raneri, Jill K.; Sola, Darlene Y.; Ahmed, Sofia B.

doi:10.1164/rccm.201502-0383oc

Cited by 63 publications

(50 citation statements)

References 45 publications

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“…292 In addition, intermittent hypoxia induces the sympathetic nervous system to increase vascular resistance, downregulates expression of the kallikrein-kallistatin vasodilator Shelley Transforming growth factor β inhibition 446 Pro-fibrotic metalloproteinase inhibition 447 Anti-fibrotic metalloproteinase activation 447 Destabilization of renal Remote ischemic pre-conditioning [384][385][386][387][388][389][390] hypoxia-inducible factor Prolyl hydroxylase inhibition 244,448 von Hippel-Lindau protein inhibition 449 pathway, and activates the renal renin-angiotensin-aldosterone system to cause vasoconstriction. [293][294][295][296][297][298][299] Together these processes conspire to produce renal fibrosis and sustained hypertension and their associated means of reducing renal oxygenation ( figure 1). 82,[300][301][302][303][304] Oxygenation is further compromised by nocturnal hypoxia altering parasympathetic control of heart rate and inducing left ventricular hypertrophy.…”

Section: Repeated Episodes Of Acute Kidney Injurymentioning

confidence: 99%

Hypoxia: The Force that Drives Chronic Kidney Disease

Colgan

Shelley

2016

Clinical Medicine & Research

129

111

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In the United States the prevalence of end-stage renal disease (ESRD) reached epidemic proportions in 2012 with over 600,000 patients being treated. The rates of ESRD among the elderly are disproportionally high. Consequently, as life expectancy increases and the baby-boom generation reaches retirement age, the already heavy burden imposed by ESRD on the US health care system is set to increase dramatically. ESRD represents the terminal stage of chronic kidney disease (CKD). A large body of evidence indicating that CKD is driven by renal tissue hypoxia has led to the development of therapeutic strategies that increase kidney oxygenation and the contention that chronic hypoxia is the final common pathway to end-stage renal failure. Numerous studies have demonstrated that one of the most potent means by which hypoxic conditions within the kidney produce CKD is by inducing a sustained inflammatory attack by infiltrating leukocytes. Indispensable to this attack is the acquisition by leukocytes of an adhesive phenotype. It was thought that this process resulted exclusively from leukocytes responding to cytokines released from ischemic renal endothelium. However, recently it has been demonstrated that leukocytes also become activated independent of the hypoxic response of endothelial cells. It was found that this endothelium-independent mechanism involves leukocytes directly sensing hypoxia and responding by transcriptional induction of the genes that encode the β2-integrin family of adhesion molecules. This induction likely maintains the long-term inflammation by which hypoxia drives the pathogenesis of CKD. Consequently, targeting these transcriptional mechanisms would appear to represent a promising new therapeutic strategy.

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Section: Repeated Episodes Of Acute Kidney Injurymentioning

confidence: 99%

Hypoxia: The Force that Drives Chronic Kidney Disease

Colgan

Shelley

2016

Clinical Medicine & Research

129

111

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“…Recently, reduced renovascular sensitivity in response to a 60-minute angiotensin II infusion was observed in OSA patients with severe nocturnal hypoxemia when compared with milder OSA patients and non-apneic, obese controls (97). No changes were observed in BP or in circulating markers of RAS activation, suggesting a specific direct impact of IH on the kidney.…”

Section: Osa As a Causative Factor In Ckdmentioning

confidence: 99%

Emerging co-morbidities of obstructive sleep apnea: cognition, kidney disease, and cancer

Gildeh¹,

Drakatos²,

Higgins³

et al. 2016

J. Thorac. Dis.

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Obstructive sleep apnea (OSA) causes daytime fatigue and sleepiness, and has an established relationship with cardiovascular and metabolic disease. Recent years have seen the emergence of an evidence base linking OSA with an increased risk of degenerative neurological disease and associated cognitive impairment, an accelerated rate of decline in kidney function with an increased risk of clinically significant chronic kidney disease (CKD), and with a significantly higher rate of cancer incidence and death. This review evaluates the evidence base linking OSA with these seemingly unrelated co-morbidities, and explores potential mechanistic links underpinning their development in patients with OSA, including intermittent hypoxia (IH), sleep fragmentation, sympathetic excitation, and immune dysregulation.

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“…Obstructive sleep apnea and chronic kidney disease: open questions on a potential public health problem were already observed in mild-moderate OSA (23), severe hypoxemia was associated with worse hemodynamic and functional renal impairment (17,25).…”

Section: Editorialmentioning

confidence: 99%

“…Conversely, other studies reporting no effect of hypoxemia mainly included subjects with mild respiratory disorders and desaturations (8). One experimental study in humans demonstrated that the more severe hypoxemia, the greater the activation of the RAS and, therefore, the more likely a renal impairment (25). Longitudinal studies used a threshold of 12% night time with SaO 2 <90% as cut-off to separate patients with and without accelerated eGFR decline (10).…”

Section: Editorialmentioning

confidence: 99%

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Obstructive sleep apnea and chronic kidney disease: open questions on a potential public health problem

Marrone

Bonsignore

2018

J. Thorac. Dis.

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Nocturnal Hypoxemia Severity and Renin–Angiotensin System Activity in Obstructive Sleep Apnea

Abstract: The severity of nocturnal hypoxemia influences the magnitude of renal, but not the systemic, RAS activation independently of obesity in patients with OSA.

Cited by 63 publications

References 45 publications

Hypoxia: The Force that Drives Chronic Kidney Disease

Hypoxia: The Force that Drives Chronic Kidney Disease

Emerging co-morbidities of obstructive sleep apnea: cognition, kidney disease, and cancer

Obstructive sleep apnea and chronic kidney disease: open questions on a potential public health problem

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