Chronobiology Of Melatonin In Ckd Patients
Melatonin, a hormone secreted by the pineal gland, is responsible for the sleep – wake circadian rhythm. It is secreted in small amounts during the daytime but increases during the night, which correlates with the onset of nocturnal sleepiness. In a small cross sectional study comparing 30 ESRD patients undergoing hemodialysis and 20 healthy participants, nocturnal melatonin levels were significantly lower in patients with ESRD. About 22 of the 30 patients also lacked the circadian rhythm in melatonin secretion. HD did not correct or improve melatonin concentrations. In another study by Karasek et al, melatonin concentrations released during the night did not improve with kidney transplantation, despite improvements in renal function. Sleep quality, as measured by actigraphy, did not significantly improve either.
Role Of Renal Replacement Therapy
In patients with ESRD on HD, intensive dialysis techniques have been shown to improve the severity of OSA . Hanly et al. have shown significant improvement in OSA of the patients who were switched from conventional HD to nocturnal HD. In a recent study in thrice-weekly HD patients, Lyons et al. performed isolated ultrafiltration on a nondialysis day in patients with AHI > 20 and found that the AHI decreased by 36% without affecting uremia, reinforcing the notion that fluid removal by UF attenuates sleep apnea without altering the uremic status. In a study of patients on peritoneal dialysis , patients performing nocturnal PD using a cycler had lower AHI during sleep compared to patients undergoing CAPD . Using bioelectrical impedance analysis, it has been shown that the total body water content is significantly lower during NPD than CAPD during sleep . Thus, preventing hypervolemia in the patients with ESRD can significantly improve OSA and resistant hypertension. Further, renal transplant in patients with ESRD has been associated with significant improvement of OSA. Thus, preventing hypervolemia in the patients with ESRD can significantly improve OSA and resistant hypertension. In a trial where a sleep study was performed before and after transplant, there was a significant decrease in AHI in OSA patients after transplant . In another study, renal transplantation was found to ameliorate sleep disturbances and lead to improvement of sleep architecture .
Are Kidney Stones Caused By Sleep Apnea
March is National Kidney Health Month so it seems an obvious choice to look into if this ailment is affected in any way by Sleep Apnea. Dr. Steven Park of New York asked the same question on his website, www.drstevenpark.com.
Here what he found out:
“One of my patients who is doing well after sleep apnea surgery emailed me a list of all the improvements just a few weeks out, and at the end, just happened to mention that he expects his kidney stones to be eradicated as well.
I didnt give it much thought, since treating sleep apnea and UARS can help almost anything, but when I went to the literature, I found a study which showed that that sleep apnea can be a direct cause of kidney stones.
What the authors showed was that uric acid excretion by the kidneys is increased in people with kidney stones. After treatment with CPAP, uric acid levels normalized.
This finding is not surprising at all, since obstructive sleep apnea is linked directly or indirectly to almost every chronic medical condition that modern people suffer from.
You would think that all patients who suffer from kidney stones would get screened for obstructive sleep apnea, but as far as I can tell, doctors havent changed their thinking about kidney stones at all.
The same thing happened after a study showed that frequent nighttime urination could be cured by treating an underlying sleep-breathing problem. Again, no major changes in the way nocturia and urinary frequency is handled.”
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What Happens When Your Co2 Level Is High
Hypercapnia is excess carbon dioxide buildup in your body. The condition, also described as hypercapnia, hypercarbia, or carbon dioxide retention, can cause effects such as headaches, dizziness, and fatigue, as well as serious complications such as seizures or loss of consciousness.
One Thought On Does Sleep Apnea Cause Kidney Disease
An FDA advisory panel just recommended yesterday that the warning label for Covidiens Optimark and GEs Omniscadrugs in the family of medications known as gadolinium-based contrast agents be updated to restrict their use in patients with severe kidney disease because of the potential for an increased risk of nephrogenic systemic fibrosis . NSF causes thickening of the skin and organs. GBCAs carry a strong black box warning. This site has good information on this issue:
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Stay Away From Caffeine And Alcohol
Caffeine and alcohol keep you up and can disrupt sleep even if you manage to fall asleep. Try to avoid nightcaps and dont consume coffee later than 2 pm. If you must have a nightcap, have it a few hours earlier than your bedtime. It takes an hour for your body to metabolize a serving of alcohol so you should have it well before you sleep.
Sleep Apnea And Kidney Disease
If you snore at night, youre probably aware of how frustrating it can be to your family. They complain that it keeps them awake half the night, but is it really that big of a deal?
If youre curious about your snoring, its generally a good idea to talk to your health care provider. Snoring is only one of the many symptoms of sleep apnea, a disorder known for causing interrupted breathing during the night. While snoring seems benign, sleep apnea is not. Sleep apnea has many deadly adverse effects including the development of kidney disease.
What is Kidney Disease?
Your kidneys are responsible for filtering your blood, producing urine to excrete excess salt and minerals, and also to produce certain hormones. Kidney disease occurs when your kidneys become damaged and are unable to properly filter your blood. This unfiltered blood builds up in your system leading to swelling, breathing problems, and even heart trauma. Kidney disease is separated by stages, each stage growing progressively worse. In many cases, youll need to have a procedure performed called dialysis where the excess fluid accumulated in your body is removed via a catheter in your abdomen or your arm. For most, dialysis is painless but comes with risks of infection or hypovolemia, the removal of too much fluid.
How Does Sleep Apnea Cause Kidney Disease?
What if I Already Have Kidney Disease?
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Evidence Of Renal Damage In Experimental Models Of Osa
OSA typically causes intermittent hypoxia during sleep. Several studies in mouse and rat models assessed the impact of IH on the kidney. A major advantage of animal models is the possibility to study the effects of IH without the confounding variables occurring in human OSA, but the IH models do not provide data on the effects of intermittent hypercapnia associated with IH in OSA. One study assessed the effects of IH and IH associated with hypercapnia and suggested a possible protective effect of CO2 on inflammatory markers, but duration of exposure was short, warranting further study .
Acute exposures to IH caused minimal or no pathological changes and increased renal blood flow and GFR . Conversely, chronic IH was associated with evidence of glomerular and tubular damage . The pathological findings included an increase in glomerular area, expansion of mesangial matrix, and increased apoptosis . As for functional changes, increased albuminuria and reduced renal flow, GFR, and sodium transport were found after chronic IH exposures .
What Causes High Carbon Dioxide Levels In A House
Abandoned mines, landfills, and caves may release CO2 into your home. This can lead to pockets of highly concentrated carbon dioxide in your home that can be very dangerous to your health. This issue is most relevant to people living in the countryside, especially in areas that used to be farmland or mining operations.
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Pathophysiology Of Ckd In Osa Patients
Renal dysfunction in OSA patients may arise via traditional risk factors for CKD associated with OSA, or it may be the result of the characteristic pathophysiological consequences of sleep disordered breathing, such as increased sympathetic output, oxidative stress, systemic inflammation, and nocturnal hypoxemia.
Definitions Of Metabolic Syndrome
Based on the modified National Cholesterol Education Programme Adult Treatment Panel III criteria, MetS) was defined as the presence of three or more of the following components: abdominal obesity, defined as a waist circumference of 90cm for men and 85cm for women hypertriglyceridemia, defined as a serum TG concentration of 150mg/dL low HDL cholesterol, defined as a serum HDL cholesterol concentration < 40mg/dL for men and < 50mg/dL for women high blood pressure, defined as a systolic blood pressure of 130mmHg, diastolic blood pressure of 85mmHg or treatment with antihypertensive agents and high fasting glucose, defined as a fasting serum glucose level of 100mg/dL or previously diagnosed type 2 diabetes.
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What Are Common Sleep Apnea Risks
Snoring, periods of stopped breathing, insomnia, and hypersomnia are common symptoms and side effects of sleep apnea. Over time, these symptoms can lead to serious problems with your overall health, especially when sleep apnea goes untreated. Below are some of the most common sleep apnea risks and side effects.
Sleep Fragmentation And Increased Sympathetic Drive
Generally considered to be mediators of the adverse cardiovascular consequences of sleep disordered breathing, sleep fragmentation and increased sympathetic tone induced by apneic events may also contribute to cancer development. As mentioned above, animal models of sleep fragmentation lead to increased tumour progression the potential immunological mechanisms behind this will be discussed below . Sleep disruption and restriction seen in shift workers are also associated with an increased risk of cancer incidence , but specific data examining the relationship between sleep fragmentation per se and cancer are lacking . Increased adrenergic signalling may also promote cancer survival and growth, although there is again a paucity of evidence specific to OSA patients in this regard .
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Alterations In Immune Function
A key effector cell in cancer biology is the macrophage, and robust evidence shows that an increase in tumour associated macrophages , particularly those with an anti-inflammatory M2 phenotype, is associated with worse outcomes in a variety of cancers . TAMs appear to promote angiogenesis, and promote tumour invasion and metastatic capacity. In a murine model of IH, TAMs showed a shift in polarity to a pro-tumoural M2 phenotype, and TAMs explanted from IH-exposed mice enhanced proliferation and invasiveness of pulmonary epithelial cancer cells in vitro .
Data examining tumour-specific immune function in OSA patients also suggests that sleep disordered breathing may contribute to a reduction in innate anti-tumoural responses. Genome sequencing in circulating leucocytes harvested from treatment-naïve patient with severe OSA revealed an upregulation in pro-neoplastic gene sets , and a subsequent downregulation in expression of these genes following approximately one month of CPAP therapy.
Overall, circumstantial, epidemiological and animal-based data support a role for OSA in promoting carcinogenesis and cancer progression. However, further mechanistic studies are required to better understand the underlying molecular alterations that underpin this association, and large scale, well designed trials of CPAP therapy will be required to demonstrate that OSA constitutes a modifiable risk factor for cancer development.
Sleep Apnea Linked To Kidney Disease In Large Study Of Veterans
Snoring is one of the signs of sleep apnea, although not all people who snore have the condition.
Obstructive sleep apneain which the airway becomes narrowed or blocked during sleepwas associated with a greater risk of kidney disease in a database study of more than 3 million VA patients.
The study is not the first to link the conditions, but it is by far the largest. The results appeared online June 2, 2015, in the journal Thorax.
“To our knowledge, this is the largest study to date to find substantial associations between a diagnosis of and kidney function decline,” wrote the authors, led by a team at the Memphis VA Medical Center and the University of Tennessee Health Sciences Center .
The study also confirmed that Veterans with sleep apnea are at greater risk for other poor health outcomes: coronary heart disease, strokes, and death from any cause.
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Conventional Ckd Risk Factors And Osa
The relationship between OSA and cardio-metabolic disorders with established links to the evolution of CKD is the subject of an extensive and growing evidence base. OSA is an independent risk factor for the development of hypertension, and appears to have independent associations with the development of atherosclerosis and diabetes mellitus prevalence and control . The potential causative role of OSA in the development of these important co-morbidities is the subject of recent dedicated reviews in the Journal of Thoracic Disease , and will not be discussed in detail here. Notably, OSA may hasten the development of diabetic nephropathy , as evidenced by an increased prevalence of OSA in subjects with DN, and an increased rate of progression of CKD in OSA patients, in a cohort of 224 type 2 diabetes followed over 2.5 years .
Systemic Inflammation And Oxidative Stress
There is a longstanding recognition that any disorder associated with chronic local or systemic inflammation may be associated with an increased risk of cancer development, an effect potentially mediated or amplified by the generation of reactive oxygen and reactive nitrogen species, with associated DNA damage and impaired DNA repair . OSA and associated IH have been demonstrated to independently contribute to the development of low-grade systemic inflammation , with increased expression of NF-B dependent cytokines in both clinical subjects and in vitro models of disease . Similarly, a significant evidence base supports the notion that OSA is an oxidative stress disorder, with reactive oxygen and nitrogen species likely formed at least partially due to IH-mediated mitochondrial dysfunction . Nocturnal CPAP therapy may lead to an abrogation of both systemic inflammation and oxidative stress, suggesting that appropriate treatment may obviate any pro-carcinogenic effect of OSA.
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Kidney Function Improves More Among Women Vs Men With Sleep Apnea Treatment
We were unable to process your request. Please try again later. If you continue to have this issue please contact .Sofia B. Ahmed
Chronic kidney disease is a growing epidemic worldwide, highlighting the urgency of identifying novel and treatable risk factors,DavidD.M. Nicholl, nephrology fellow at Western University, and Sofia B. Ahmed, MD MMSc, FRCPC, of the University of Calgary, Canada, told Healio Nephrology. Obstructive sleep apnea is common in CKD and associated with increased kidney risk. Sleep apnea typically affects more men than women. However, women with sleep apnea are less likely to be diagnosed and treated and may therefore be at increased risk from untreated sleep apnea. We know from our previous work that treatment of OSA with continuous positive airway pressure improved renal hemodynamics and renin angiotensin system activity , but whether there were sex differences in kidney function in patients with sleep apnea was unknown.
To investigate, researchers recruited 10 women and 19 men who had obstructive sleep apnea with nocturnal hypoxemia, but no history of kidney disease. All participants were assessed before and after CPAP therapy .
However, while CPAP downregulated the renin angiotensin system activity in women, this effect was not seen in men.
Disclosures: The authors report no relevant financial disclosures.
Esrd Management And Osa
The potential impact of ESRD management on sleep apnea was elegantly shown in an intervention trial by Hanly et al. These investigators switched 14 ESRD patients from conventional 3 times/week hemodialysis to 67 times/week nocturnal hemodialysis at home. After 615 months, average AHI was reduced from 25 to 8 episodes/h of sleep . The potential mechanisms of improvement in OSA symptoms were not evaluated in this study. An earlier case of 2 ESRD patients with severe OSA and central sleep apnea reported an absence of sleep apnea symptoms, with reductions in AHI to 9 and 5, respectively, after undergoing renal transplantation.
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Osa Management And Kidney Function
Treatment of moderate to severe OSA by CPAP positively affects kidney filtration by minimizing glomerular hyperfiltration, which is common in many renal disorders. Kinebuchi et al. compared the filtration fractions of 21 patients with moderate-to-severe OSA before and after CPAP treatment, considering filtration fractions and renal plasma flows as indicators of glomerular hyperfiltration. Short-term CPAP therapy significantly reduced hyperfiltration by increasing renal plasma flow and reducing the filtration fraction. Another recent study examined the effects of short-term CPAP treatment on kidney function in 27 men with polysomnography-diagnosed OSA . Three months of CPAP treatment decreased average serum creatinine levels , and increased average eGFR levels from 72.9 to 79.3 mg/dL these changes were statistically significant but with unreported clinical benefits. Findings from this study are limited by the lack of a control group and adjustment for other potential confounders.
Osa As A Causative Factor In Ckd
Pathways through which sleep disordered breathing may exert a direct impact on renal function include alterations in glomerular perfusion mediated by OSA-related changes in sympathetic tone, neurohumeral output, and endothelial function, alongside tubulointerstitial hypoxia due to repetitive nocturnal fluctuations in oxygen tension . Low grade systemic inflammation promotes endothelial dysfunction and subsequent atherosclerosis, and occurs in OSA patients as a direct result of nocturnal IH . Similarly, IH promotes the generation of free oxygen radicals, with the consequent oxidative stress exerting a detrimental effect on the vascular endothelium , while apneic events also lead to increased sympathetic outflow, leading to profound alterations in vascular tone . In a study comparing healthy controls with newly diagnosed patients with moderate to severe OSA, but free of cardiovascular risk factors, the OSA patients showed evidence of endothelial dysfunction, impaired renal vasodilation and reduced endothelial nitric oxide synthase expression, despite a lack of overt signs of end organ disease. This suggests that OSA in itself is an independent risk factor for clinically occult renal endothelial damage which is not clinically detectible, which may then proceed to overt renal dysfunction .
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