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No abstract available.
Epidemiological studies demonstrate an association between obstructive sleep apnea (OSA) and accelerated loss of kidney function. OSA is characterized by repetitive episodes of intermittent hypoxia (IH) during sleep, which provokes systemic and renal oxidative stress and inflammation. Here we hypothesized that IH induces structural and functional renal injury by increasing glomerular growth factors, increasing oxidative stress and inflammation, and that α-lipoic acid (LA), an antioxidant, attenuates this injury. To address this hypothesis, the ability of LA to mitigate the structural and functional aspects of renal injury secondary to IH was examined.Ten 8-week old wild-type male CB57BL/6 mice were randomly assigned to receive either IH or intermittent air (IA) for 60 days. The first study involved histological measurements of glomerular area and mesangial matrix expansion (MME), where glomerular growth factors were quantified by immunohistochemistry. Renal cellular apoptosis was investigated by measuring apoptotic proteins in kidney cortex. Finally, measurements of renal function were made by measuring serum creatinine and 24-hour urinary albumin. For the second study, 20 mice were randomized to receive either IH or IA, with regular diet (RD) or 0.2% w/w LA-enriched diet. After 60 days, samples of urine and plasma were collected. Markers for oxidative stress, inflammation, apoptosis, and tubular injury in kidney cortex were quantified. Glomerular area and MME were measured as well.Compared to controls, IH-exposed mice had increased glomerular areas and MME, accompanied by increases in glomerular growth factors and cellular apoptosis markers. IH-exposed mice had increases in albuminuria but not in serum creatinine. The second study demonstrated reduced urinary albumin excretion in the IH-LA group compared to IH-RD. Histological assessment showed significant increases in glomerular area of IH-RD compared to IH-LA. Treatment with LA also normalized systemic and renal oxidative stress and inflammation, and attenuated renal cellular apoptosis and tubular injury secondary to IH.These findings indicate for the first time that IH causes structural and functional kidney injury and increases renal cellular apoptosis, and this injury was attenuated by the antioxidant effect of LA. Treatment with LA may be a potentially promising therapy to reduce renal dysfunction in patients with OSA.
Background: Obstructive Sleep Apnea (OSA) is a common but under diagnosed respiratory disorder characterized by recurrent upper airway obstruction during sleep. OSA results in sleep fragmentation and hypoxemia and is associated with neurocognitive impairments. OSA negatively affects vigilance and work performance, yet there is limited evidence on the relationship between OSA and the risk of occupational injuries (OI). It is hypothesized that individuals with OSA would have an increased risk of OI, and that OSA treatment may reduce this risk. Dissertation Objectives:1. Summarize the existing evidence on the relationship between OSA and OI (Chapter 1).2. Evaluate the association between the presence and severity of OSA and the risk of OI, both before and after diagnosis (Chapters 2-4). 3. Evaluate the impact of Continuous Positive Airway Pressure (CPAP) treatment on the risk of OI (Chapter 5).Methods: Patients referred to the UBC Sleep Disorders Clinic (SDC) for suspected OSA (2003-2011) were recruited to participate and diagnosed with OSA using polysomnography (PSG). Rates and risk of OI in the five years pre and post-PSG were calculated and compared by OSA status by linking to workers claims data. In addition, a matched sample of residents linked to claims data was drawn from the provincial health registry and compared to the OSA group. CPAP adherence data was collected from all OSA patients whose charts were available, and the impact of CPAP on the risk of OI was assessed using a pre/post treatment design.