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Battaglia E, Compalati E, Mapelli L, Lax A, Pierucci P, Solidoro P, Banfi P. Pulmonary hypertension in patients affected by sleep-related breathing disorders: up to date from the literature. Minerva Med 2024; 115:671-688. [PMID: 39016524 DOI: 10.23736/s0026-4806.24.09112-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/18/2024]
Abstract
Sleep-related breathing disorders (SBD) are conditions of abnormal and difficult respiration during sleep, including chronic snoring, obstructive sleep apnea (OSA), central sleep apnea (CSA), sleep-related hypoventilation disorders and sleep-related hypoxemia. Some of them have a limited impact on health, but others (e.g., OSA) can have serious consequences, because of their dangerous effects on sleep and the hematic balance of oxygen and carbon dioxide. According to several population-based studies, prevalence of OSA is relatively high, approximately 3-7% for adult males and 2-5% for adult females in the general population. However, methodological differences and difficulties in characterizing this syndrome yielded to variability in estimates. Moreover, it is estimated that only about 40% of patients with OSA are diagnosed, which can lead to underestimation of disease prevalence. OSA is directly correlated with age and male sex and to risk factors such as obesity. Several studies found that OSA is associated with an increased risk of diabetes, some cancer types, cardiovascular and cerebrovascular diseases, such as hypertension, coronary artery disease and stroke. Pulmonary hypertension (PH), a noted cardiovascular disease, is significantly associated with sleep-related breathing disorders and lot of scientific studies published in the literature demonstrated a strong link between these conditions and the development of pulmonary hypertension PH. PH is relatively less common than sleep-related breathing disorders. The purpose of this systematic review is to analyze both the current knowledge around the consequences that SBD may have on pulmonary hemodynamics and the effects resulting from pharmacological and non-pharmacological treatments of SDB on PH.
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Affiliation(s)
| | | | - Luca Mapelli
- IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy
| | - Agata Lax
- IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy
| | - Paola Pierucci
- Department of Cardiothoracic Surgery, Bari Polyclinic Hospital, Bari, Italy
| | | | - Paolo Banfi
- IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy
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2
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Kasai T, Kohno T, Shimizu W, Ando S, Joho S, Osada N, Kato M, Kario K, Shiina K, Tamura A, Yoshihisa A, Fukumoto Y, Takata Y, Yamauchi M, Shiota S, Chiba S, Terada J, Tonogi M, Suzuki K, Adachi T, Iwasaki Y, Naruse Y, Suda S, Misaka T, Tomita Y, Naito R, Goda A, Tokunou T, Sata M, Minamino T, Ide T, Chin K, Hagiwara N, Momomura S. JCS 2023 Guideline on Diagnosis and Treatment of Sleep Disordered Breathing in Cardiovascular Disease. Circ J 2024; 88:1865-1935. [PMID: 39183026 DOI: 10.1253/circj.cj-23-0489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/27/2024]
Affiliation(s)
- Takatoshi Kasai
- Division of School of Health Science, Department of Pathobiological Science and Technology, Faculty of Medicine, Tottori University
| | - Takashi Kohno
- Department of Cardiovascular Medicine, Kyorin University Faculty of Medicine
| | - Wataru Shimizu
- Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School
| | - Shinichi Ando
- Sleep Medicine Center, Fukuokaken Saiseikai Futsukaichi Hospital
| | - Shuji Joho
- Second Department of Internal Medicine, University of Toyama
| | - Naohiko Osada
- Department of Cardiology, St. Marianna University School of Medicine
| | - Masahiko Kato
- Division of School of Health Science, Department of Pathobiological Science and Technology, Faculty of Medicine, Tottori University
| | - Kazuomi Kario
- Division of Cardiovascular Medicine, Department of Medicine, Jichi Medical University School of Medicine
| | | | | | - Akiomi Yoshihisa
- Department of Clinical Laboratory Sciences, Fukushima Medical University School of Health Science
- Department of Cardiovascular Medicine, Fukushima Medical University
| | - Yoshihiro Fukumoto
- Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine
| | | | - Motoo Yamauchi
- Department of Clinical Pathophysiology of Nursing and Department of Respiratory Medicine, Nara Medical University
| | - Satomi Shiota
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine
| | | | - Jiro Terada
- Department of Respiratory Medicine, Japanese Red Cross Narita Hospital
| | - Morio Tonogi
- 1st Depertment of Oral & Maxillofacial Surgery, Nihon Univercity School of Dentistry
| | | | - Taro Adachi
- Division of Cardiology, Department of Medicine, Showa University School of Medicine
| | - Yuki Iwasaki
- Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School
| | - Yoshihisa Naruse
- Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine
| | - Shoko Suda
- Department of Cardiovascular Medicine, Juntendo University School of Medicine
| | - Tomofumi Misaka
- Department of Clinical Laboratory Sciences, Fukushima Medical University School of Health Science
- Department of Cardiovascular Medicine, Fukushima Medical University
| | | | - Ryo Naito
- Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine
| | - Ayumi Goda
- Department of Cardiovascular Medicine, Kyorin University Faculty of Medicine
| | - Tomotake Tokunou
- Division of Cardiology, Department of Medicine, Fukuoka Dental College
| | - Makoto Sata
- Department of Pulmonology and Infectious Diseases, National Cerebral and Cardiovascular Center
| | | | - Tomomi Ide
- Faculty of Medical Sciences, Kyushu University
| | - Kazuo Chin
- Graduate School of Medicine and Faculty of Medicine, Kyoto University
| | - Nobuhisa Hagiwara
- YUMINO Medical Corporation
- Department of Cardiology, Tokyo Women's Medical University
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3
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Lyons OD. Sleep disorders in chronic kidney disease. Nat Rev Nephrol 2024; 20:690-700. [PMID: 38789686 DOI: 10.1038/s41581-024-00848-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/02/2024] [Indexed: 05/26/2024]
Abstract
Sleep disorders are highly prevalent in chronic kidney disease (CKD) but are often under-recognized. Restless legs syndrome, which is common in CKD owing to issues with dopamine metabolism and is exacerbated by iron deficiency and uraemia, can lead to poor sleep quality and increased daytime fatigue. Insomnia is also prevalent in CKD, particularly in patients requiring dialysis, with increased sleep latency and sleep fragmentation being reported. The cause of insomnia in CKD is multifactorial - poor sleep habits and frequent napping during dialysis, uraemia, medications and mood disorders have all been suggested as potential contributing factors. Sleep apnoea and CKD are also now recognized as having a bi-directional relationship. Sleep apnoea is a risk factor for accelerated progression of CKD, and fluid overload, which is associated with kidney failure, can lead to both obstructive and central sleep apnoea. The presence of obstructive sleep apnoea in CKD can exacerbate the already heightened cardiovascular morbidity and mortality in these patients, as well as leading to daytime fatigue and reduced quality of life. Increased awareness, timely diagnosis and appropriate therapeutic interventions are essential to reduce the negative impact of sleep disorders in patients with kidney disease.
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Affiliation(s)
- Owen D Lyons
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
- Department of Medicine, Women's College Hospital, Toronto, Canada.
- Women's College Research Institute, Toronto, Ontario, Canada.
- Sleep Research Laboratory, Toronto Rehabilitation Institute, KITE-UHN, Toronto, Ontario, Canada.
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4
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Tao LL, Zeng CH, Mei WJ, Zou YL. Sleep quality in middle-aged and elderly hemodialysis patients: Impact of a structured nursing intervention program. World J Clin Cases 2024; 12:5713-5719. [PMID: 39247744 PMCID: PMC11263055 DOI: 10.12998/wjcc.v12.i25.5713] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 06/14/2024] [Accepted: 07/01/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND Poor sleep quality is common among hemodialysis patients and can significantly impact their well-being. This study aimed to evaluate the effectiveness of a structured nursing intervention program in improving sleep quality in middle-aged and elderly hemodialysis patients. AIM To evaluate the impact of nursing intervention on sleep quality in hemodialysis patients. METHODS This cross-sectional study was conducted in a tertiary hospital, the First Affiliated Hospital of Nanchang University, in 2023. This study included 105 middle-aged and elderly hemodialysis patients aged ≥ 45 years who underwent maintenance hemodialysis for at least 3 mo, utilizing the Pittsburgh Sleep Quality Index (PSQI) to identify poor sleepers. Those identified underwent a 12-wk nursing intervention program focusing on education, relaxation techniques, and counseling. Post-intervention, sleep quality was reassessed using the PSQI. RESULTS The study found that 68.6% of hemodialysis patients were poor sleepers. Following the 12-wk nursing intervention program, there was a significant decrease in the mean global PSQI score from 8.9 ± 3.2 to 5.1 ± 2.7 (P < 0.001), indicating improved sleep quality. This demonstrated the effectiveness of the structured nursing intervention in enhancing sleep quality for middle-aged and elderly hemodialysis patients. CONCLUSION The structured nursing intervention program focusing on sleep hygiene education, relaxation techniques, and counseling effectively improved sleep quality among middle-aged and elderly hemodialysis patients. The significant decrease in the mean global PSQI score post-intervention indicates the positive impact of tailored nursing interventions in addressing poor sleep quality in this patient population. These findings emphasize the importance of implementing targeted nursing interventions to enhance the quality of life for hemodialysis patients by addressing the prevalent issue of poor sleep quality.
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Affiliation(s)
- Ling-Ling Tao
- Blood Purification Room, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Cai-Hua Zeng
- Blood Purification Room, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Wen-Juan Mei
- Blood Purification Room, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
| | - Yan-Li Zou
- Blood Purification Room, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
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Diaz S, Abad K, Patel SR, Unruh ML. Emerging Treatments for Insomnia, Sleep Apnea, and Restless Leg Syndrome Among Dialysis Patients. Semin Nephrol 2022; 41:526-533. [PMID: 34973697 DOI: 10.1016/j.semnephrol.2021.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Sleep disturbances are highly prevalent in patients with predialysis chronic kidney disease, end-stage kidney disease, and after a kidney transplant. They contribute to impairment in daily function and are associated with a high burden of physical and psychiatric symptoms, decreased quality of life, and increased morbidity and mortality. Sleep disturbances also may precipitate and accelerate kidney disease progression. They often evolve across the spectrum of kidney dysfunction and may persist or re-emerge in kidney transplant recipients. Investigation into the multifaceted and dynamic relationships between sleep disturbance and chronic kidney disease requires consideration of myriad contributors including the progression of kidney disease itself, the role of treatment via dialysis and kidney transplant, psychosocial factors, and underlying sleep disorders. Despite sleep disturbance being identified as a priority to address by patients and caregivers, sleep disorders including insomnia, sleep apnea, and restless leg syndrome remain under-recognized and undertreated, and innovation in their management remains modest. In this article, we review the relationships between sleep disturbance and kidney disease, the impact of sleep disturbance and sleep disorders on symptom burden and mental health, and treatment opportunities that may address overlapping symptoms across the spectrum of kidney disease and that could improve patient-related and clinical outcomes.
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Affiliation(s)
- Shanna Diaz
- Department of Internal Medicine, University of New Mexico, Albuquerque, NM
| | - Kashif Abad
- Department of Internal Medicine, University of New Mexico, Albuquerque, NM
| | - Sanjay R Patel
- Pulmonary, Sleep and Critical Care, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Mark L Unruh
- Department of Internal Medicine, University of New Mexico, Albuquerque, NM; Nephrology Section, New Mexico Veterans Hospital, Albuquerque, NM.
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6
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Voulgaris A, Bonsignore MR, Schiza S, Marrone O, Steiropoulos P. Is kidney a new organ target in patients with obstructive sleep apnea? Research priorities in a rapidly evolving field. Sleep Med 2021; 86:56-67. [PMID: 34474225 DOI: 10.1016/j.sleep.2021.08.009] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 07/15/2021] [Accepted: 08/05/2021] [Indexed: 11/28/2022]
Abstract
The bidirectional relationship between sleep disordered breathing and chronic kidney disease (CKD) has recently gained a lot of interest. Several lines of evidence suggest the high prevalence of coexistent obstructive sleep apnea (OSA) in patients with CKD and end-stage renal disease (ESRD). In addition, OSA seems to result in loss of kidney function in some patients, especially in those with cardio-metabolic comorbidities. Treatment of CKD/ESRD and OSA can alter the natural history of each other; still better phenotyping with selection of appropriate treatment approaches is urgently needed. The aim of this narrative review is to provide an update of recent studies on epidemiological associations, pathophysiological interactions, and management of patients with OSA and CKD or ESRD.
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Affiliation(s)
- Athanasios Voulgaris
- MSc Programme in Sleep Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece; Department of Respiratory Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Maria R Bonsignore
- Institute of Biomedicine and Molecular Immunology, CNR, Palermo, Italy; Sleep Disordered Breathing and Chronic Respiratory Failure Clinic, PROMISE Department, University of Palermo, and IRIB, National Research Council (CNR), Palermo, Italy
| | - Sophia Schiza
- Sleep Disorders Center, Department of Respiratory Medicine, Medical School, University of Crete, Heraklion, Greece
| | - Oreste Marrone
- Institute of Biomedicine and Molecular Immunology, CNR, Palermo, Italy
| | - Paschalis Steiropoulos
- MSc Programme in Sleep Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece; Department of Respiratory Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
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Rimke AN, Ahmed SB, Turin TC, Pendharkar SR, Raneri JK, Lynch EJ, Hanly PJ. Recruitment of patients with chronic kidney disease and obstructive sleep apnoea for a clinical trial. J Sleep Res 2021; 30:e13384. [PMID: 33973687 DOI: 10.1111/jsr.13384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 02/05/2021] [Accepted: 04/19/2021] [Indexed: 11/27/2022]
Abstract
Obstructive sleep apnoea is common in chronic kidney disease (CKD) and may accelerate the decline in kidney function. Recruitment for a randomised controlled trial to address whether treatment of sleep apnoea with continuous positive airway pressure (CPAP) slows the progression of kidney failure may be challenging because sleep apnoea is often asymptomatic in this patient population. The present report outlines recruitment challenges and how to address them. Adult patients with CKD were recruited for a 12-month randomised, controlled, non-blinded, parallel clinical trial to evaluate the impact of CPAP therapy on kidney function. Patients completed a home sleep apnoea test and those that met pre-specified sleep apnoea and nocturnal hypoxaemia severity criteria were randomised to receive CPAP or no therapy. Although 1,665 patients were eligible to participate in the study over 3 years, only 57 (3.4%) were ultimately randomised. The sequential reasons (and number of patients) for recruitment failure were: no show at clinic appointment (137), insufficient recruiters to approach every eligible patient (461), on therapy for sleep apnoea (122), unable to provide informed consent (67), refused consent (645), home sleep apnoea test not completed (47) or inclusion criteria not met (116), and declined pre-randomisation education session (12). Many challenges limit effective recruitment, which may be addressed by hiring additional recruiters and increasing the awareness of sleep apnoea among patients with CKD. These findings can be used to improve recruitment strategies and the design of future studies.
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Affiliation(s)
- Alex N Rimke
- Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada.,Libin Cardiovascular Institute of Alberta, Calgary, AB, Canada
| | - Sofia B Ahmed
- Libin Cardiovascular Institute of Alberta, Calgary, AB, Canada.,Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Alberta Kidney Disease Network, Calgary, AB, Canada
| | - Tanvir C Turin
- Department of Family Medicine, University of Calgary, Calgary, AB, Canada
| | - Sachin R Pendharkar
- Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada.,Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Jill K Raneri
- Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada
| | - Emma J Lynch
- Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada
| | - Patrick J Hanly
- Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada.,Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.,Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada
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8
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Rimke AN, Ahmed SB, Turin TC, Pendharkar SR, Raneri JK, Lynch EJ, Hanly PJ. Effect of CPAP Therapy on Kidney Function in Patients With Chronic Kidney Disease: A Pilot Randomized Controlled Trial. Chest 2020; 159:2008-2019. [PMID: 33316238 DOI: 10.1016/j.chest.2020.11.052] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 11/22/2020] [Accepted: 11/25/2020] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND OSA is common in chronic kidney disease (CKD) and may accelerate a decline in kidney function. It is not clear whether treatment of OSA with CPAP improves kidney function. RESEARCH QUESTION Does treatment with CPAP improve kidney function in patients with CKD and coexisting OSA? STUDY DESIGN AND METHODS A randomized, controlled, nonblinded, parallel clinical trial was performed of patients with stages 3 and 4 CKD and coexisting OSA comparing the effect of CPAP vs usual care on the estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (ACR) over 12 months. RESULTS Fifty-seven patients were enrolled and 30 were randomized to CPAP. They had moderately severe CKD (eGFR, 38.4 ± 1.5 mL/min/1.73 m2) and significant OSA and nocturnal hypoxemia (oxygen desaturation index: 23.9 events/h; interquartile range [IQR], 20.3 events/h; mean peripheral capillary oxygen saturation: 89.5%; IQR, 1.7%); 60% had baseline albuminuria (ACR, > 3 mg/mmol). No significant difference was found between CPAP and usual care in the change in eGFR and ACR over 12 months. Although some improvement in eGFR occurred with CPAP therapy in patients with a lower risk of CKD progression, this did not reach statistical significance. INTERPRETATION Although CPAP did not provide additional renal benefits over usual care in all CKD patients, some evidence suggested that CPAP slowed the decline in eGFR in CKD patients with a lower risk of CKD progression. These preliminary data support the need for larger clinical trials exploring the effects of CPAP on kidney function. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT02420184; URL: www.clinicaltrials.gov.
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Affiliation(s)
- Alex N Rimke
- Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada; Libin Cardiovascular Institute of Alberta, Calgary, AB, Canada
| | - Sofia B Ahmed
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Libin Cardiovascular Institute of Alberta, Calgary, AB, Canada; Alberta Kidney Disease Network, Calgary, AB, Canada
| | - Tanvir C Turin
- Department of Family Medicine, University of Calgary, Calgary, AB, Canada
| | - Sachin R Pendharkar
- Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Jill K Raneri
- Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada
| | - Emma J Lynch
- Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada
| | - Patrick J Hanly
- Sleep Centre, Foothills Medical Centre, University of Calgary, Calgary, AB, Canada; Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
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Chu G, Price E, Paech GM, Choi P, McDonald VM. Sleep Apnea in Maintenance Hemodialysis: A Mixed-Methods Study. Kidney Med 2020; 2:388-397. [PMID: 32775978 PMCID: PMC7406845 DOI: 10.1016/j.xkme.2020.02.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Rationale & Objective More than 50% of hemodialysis patients experience sleep disturbance and most have coexisting sleep apnea. However, how sleep apnea affects sleep and the overall experience of patients with chronic kidney disease treated by hemodialysis has not been evaluated. Study Design A mixed-methods design, incorporating cross-sectional observational and descriptive qualitative methodologies. Setting & Participants Patients receiving maintenance hemodialysis in Newcastle, New South Wales, Australia, with newly diagnosed sleep apnea (apnea-hypopnea index ≥ 5 per hour). Assessments In-laboratory polysomnography to assess sleep apnea and objective sleep parameters. Epworth Sleepiness Scale to assess daytime symptoms. A semi-structured qualitative interview to explore patient experience. Analytical Approach Descriptive and iterative thematic analysis. Results We analyzed 36 patients with newly diagnosed sleep apnea and interviewed 26 (mean age, 62 years, median apnea-hypopnea index, 32 per hour). Severity of sleep apnea did not affect patients’ sleep duration, sleep efficiency, or self-reported Epworth Sleepiness Scale score. From the qualitative interviews, 4 themes emerged: “broken sleep” related to short sleep duration, with waking and dozing off a common sleep cycle, caused by uncontrolled pain and dialysis. Many participants reported regularly “feeling unrefreshed” on waking. “Impact of sleep disturbance” included reduced physical, mental, and self-management capacity. Finally, interviewees described the need to use strategies to “soldier on” with symptoms. Limitations Participants’ views are only transferrable to hemodialysis patients with sleep apnea. Conclusions Our findings suggest that severity of sleep apnea does not affect sleep time or patient-reported daytime sleepiness; however, hemodialysis patients with sleep apnea report disturbed and unrefreshed sleep and the debilitating effects of sleep disturbance is profound. Broken and unrefreshed sleep were the dominant symptoms of sleep apnea and should be assessed routinely to identify patients with sleep apnea and improve quality of life in patients with chronic kidney disease treated with hemodialysis.
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Affiliation(s)
- Ginger Chu
- Department of Nephrology, Medical and Interventional Services, John Hunter Hospital, Hunter New England Local Health District New South Wales, Australia.,School of Nursing and Midwifery, University of Newcastle New South Wales, Australia.,Research, Innovation and Partnerships, Hunter New England Local Health District New South Wales, Australia.,Priority Research Centre for Healthy Lungs, University of Newcastle New South Wales, Australia
| | - Emma Price
- Department of Nephrology, Medical and Interventional Services, John Hunter Hospital, Hunter New England Local Health District New South Wales, Australia
| | - Gemma M Paech
- School of Medicine and Public Health University of Newcastle New South Wales, Australia.,Department of Respiratory and Sleep Medicine, Medical and Interventional Services, John Hunter Hospital, Hunter New England Local Health District, New South Wales, Australia
| | - Peter Choi
- Department of Nephrology, Medical and Interventional Services, John Hunter Hospital, Hunter New England Local Health District New South Wales, Australia
| | - Vanessa M McDonald
- School of Nursing and Midwifery, University of Newcastle New South Wales, Australia.,Priority Research Centre for Healthy Lungs, University of Newcastle New South Wales, Australia.,Department of Respiratory and Sleep Medicine, Medical and Interventional Services, John Hunter Hospital, Hunter New England Local Health District, New South Wales, Australia
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10
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Abstract
Abstract
Purpose of Review
There are some uncertainties about the interactions between obstructive sleep apnea (OSA) and chronic kidney disease (CKD). We critically reviewed recent studies on this topic with a focus on experimental and clinical evidence of bidirectional influences between OSA and CKD, as well as the effects of treatment of either disease.
Recent Findings
Experimental intermittent hypoxia endangers the kidneys, possibly through activation of inflammatory pathways and increased blood pressure. In humans, severe OSA can independently decrease kidney function. Treatment of OSA by CPAP tends to blunt kidney function decline over time, although its effect may vary. OSA may increase cardiovascular complications and mortality in patients with end-stage renal disease (ESRD), while it seems of little harm after renal transplantation. Excessive fluid removal may explain some of the improvements in OSA severity in ESRD and after transplantation.
Summary
Severe OSA and CKD do interact negatively, mainly through hypoxia and fluid retention. The moderate mutually interactive benefits that treatment of each disease exerts on the other one warrant further studies to improve patient management.
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11
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Lin CH, Lurie RC, Lyons OD. Sleep Apnea and Chronic Kidney Disease. Chest 2020; 157:673-685. [DOI: 10.1016/j.chest.2019.09.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2019] [Revised: 08/20/2019] [Accepted: 09/01/2019] [Indexed: 12/20/2022] Open
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12
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Canales MT, Bozorgmehri S, Ishani A, Weiner ID, Berry R, Beyth R. Prevalence and correlates of sleep apnea among US Veterans with chronic kidney disease. J Sleep Res 2020; 29:e12981. [PMID: 31912641 DOI: 10.1111/jsr.12981] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 10/30/2019] [Accepted: 12/12/2019] [Indexed: 12/12/2022]
Abstract
The prevalence and correlates of sleep apnea (SA) among Veterans with chronic kidney disease (CKD), a population at high risk of both SA and CKD, are unknown. We performed a cross-sectional analysis of 248 Veterans (18-89 years) selected only for presence of moderate to severe CKD. All participants underwent full, unattended polysomnography, measurement of renal function and a sleepiness questionnaire. Logistic regression with backward selection was used to identify predictors of prevalent SA (apnea-hypopnea index [AHI, ≥15 events/hr] and prevalent nocturnal hypoxia [NH, % of total sleep time spent at <90% oxygen saturation]). The mean age of our cohort was 73.2 ± 9.6 years, 95% were male, 78% were Caucasian and the mean body mass index (BMI) was 30.3 ± 4.8 kg/m2 . The prevalence of SA was 39%. There was no difference in daytime sleepiness among those with and without SA. In the final model, older age, higher BMI and diabetes mellitus (DM) were associated with higher odds of SA, after controlling for age, BMI, race and sex. Higher BMI, DM, unemployed/retired status, current smoking and higher serum bicarbonate level were associated with prevalent NH. To sum, SA was common among Veterans with moderate to severe CKD. Although some traditional risk factors for SA were associated with SA in this population, sleepiness did not correlate with SA. Further study is needed to validate our findings and understand how best to address the high burden of SA among Veterans with CKD.
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Affiliation(s)
- Muna T Canales
- Division of Nephrology, Department of Medicine, Malcom Randall VA Medical Center, University of Florida, Gainesville, FL, USA
| | - Shahab Bozorgmehri
- Division of Nephrology, Department of Medicine, Malcom Randall VA Medical Center, University of Florida, Gainesville, FL, USA
| | - Areef Ishani
- Minneapolis VA Medical Center, University of Minnesota, Minneapolis, MN, USA
| | - I David Weiner
- Division of Nephrology, Department of Medicine, Malcom Randall VA Medical Center, University of Florida, Gainesville, FL, USA
| | - Richard Berry
- Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, Malcom Randall VA Medical Center, University of Florida, Gainesville, FL, USA
| | - Rebecca Beyth
- Division of General Medicine, Department of Medicine, Malcom Randall VA Medical Center, University of Florida, Gainesville, FL, USA
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13
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Nicholl DDM, Hanly PJ, Zalucky AA, Handley GB, Sola DY, Ahmed SB. Sex differences in renal hemodynamics and renin-angiotensin system activity post-CPAP therapy in humans with obstructive sleep apnea. Am J Physiol Renal Physiol 2019; 318:F25-F34. [PMID: 31608672 DOI: 10.1152/ajprenal.00290.2019] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
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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Affiliation(s)
- David D M Nicholl
- Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
| | - Patrick J Hanly
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Sleep Centre, Foothills Medical Centre, Calgary, Alberta, Canada.,Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada
| | - Ann A Zalucky
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | | | - Darlene Y Sola
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada
| | - Sofia B Ahmed
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.,Sleep Centre, Foothills Medical Centre, Calgary, Alberta, Canada.,Alberta Kidney Disease Network, Canada
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14
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Lendvai Z, Pásti K, Szeifert L, Molnár LD, Rusai K, Balassa K, Reusz G, Szabó AJ. Cardiometabolic correlates of sleep-disordered breathing in renal transplant children. Pediatr Transplant 2019; 23:e13529. [PMID: 31259462 DOI: 10.1111/petr.13529] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2019] [Revised: 05/25/2019] [Accepted: 05/29/2019] [Indexed: 11/29/2022]
Abstract
Sleep-disordered breathing, a prevalent condition among adult renal transplant (RTx) recipients, has become an established independent risk factor of MetS, and furthermore, it might contribute to increased CV risk. Despite the proven correlations in adults, there is a lack of evidence for its significance in the pediatric RTx population. In this study, we aimed at assessing the prevalence and the clinical correlates of SDB in RTx children. Data of 13 patients (age [mean ± SD]: 14.2 ± 2.7 years) were analyzed. SDB was evaluated by PSG, as severity score OAHI was applied. Carbohydrate metabolism was characterized by OGTT, whereas CV status was studied by ABPM. Three composite end-points were calculated as sum of z-scores: daytime systolic and diastolic BP; nighttime systolic and diastolic BP; and glucose and insulin levels at 120 minutes. Eight patients (61.5%) were diagnosed with SDB of whom five patients (38.5%) had moderate or severe SDB. In linear regression analysis, OAHI during REM was associated with the CV variables (daytime BP P = 0.032, ß = 0.748; nighttime BP P = 0.041, ß = 0.715), and the correlations remained significant after adjustments for BMI. However, we did not confirm a significant association with the metabolic variables. The prevalence of SDB was high, and its severity during REM was a predictor of the BP suggesting that RTx children with SDB might be at risk of developing CV complications, especially HTN similarly to adults.
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Affiliation(s)
- Zsófia Lendvai
- First Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Krisztina Pásti
- First Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Lilla Szeifert
- First Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | | | - Krisztina Rusai
- Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Medical University Vienna, Vienna, Austria
| | - Katalin Balassa
- Department of Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - George Reusz
- First Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Attila J Szabó
- First Department of Pediatrics, Semmelweis University, Budapest, Hungary.,Pediatrics and Nephrology Research Group, Hungarian Academy of Sciences-Semmelweis University, Budapest, Hungary
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15
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Zomorodi K, Chen D, Lee L, Lasseter K, Marbury T. Single-Dose Pharmacokinetics and Safety of Solriamfetol in Participants With Normal or Impaired Renal Function and With End-Stage Renal Disease Requiring Hemodialysis. J Clin Pharmacol 2019; 59:1120-1129. [PMID: 30865315 PMCID: PMC6618134 DOI: 10.1002/jcph.1402] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 01/30/2019] [Indexed: 01/05/2023]
Abstract
Solriamfetol (JZP-110), a selective dopamine and norepinephrine reuptake inhibitor with wake-promoting effects, is renally excreted ∼90% unchanged within 48 hours. Effects of renal impairment and hemodialysis on the pharmacokinetics and safety of 75-mg single-dose solriamfetol were evaluated in adults with normal renal function (n = 6); mild (n = 6), moderate (n = 6), or severe (n = 6) renal impairment; and end-stage renal disease (ESRD) with and without hemodialysis (n = 7). Relative to normal renal function, geometric mean area under the plasma concentration-time curve from time zero to infinity increased 53%, 129%, and 339%, and mean half-life was 1.2-, 1.9-, and 3.9-fold higher with mild, moderate, and severe renal impairment, respectively. Renal excretion of unchanged solriamfetol over 48 hours was 85.8%, 80.0%, 66.4%, and 57.1% in normal, mild, moderate, and severe renal impairment groups, respectively; mean maximum concentration and time to maximum concentration did not vary substantially. Decreases in solriamfetol clearance were proportional to decreases in estimated glomerular filtration rate. Geometric mean area under the plasma concentration-time curve from time zero to time of last quantifiable concentration increased 357% and 518% vs normal in ESRD with and without hemodialysis, respectively, with half-life >100 hours in both groups. Over the 4-hour hemodialysis period, ∼21% of solriamfetol dose was removed. Adverse events included headache (n = 1) and nausea (n = 1). Six days after dosing, 1 participant had increased alanine and aspartate aminotransferase, leading to study discontinuation. While these adverse events were deemed study-drug related, they were mild and resolved. Results from this study combined with population pharmacokinetic modeling/simulation suggest that solriamfetol dosage adjustments are necessary in patients with moderate or severe but not with mild renal impairment. Due to significant exposure increase/prolonged half-life, dosing is not recommended in patients with ESRD.
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Affiliation(s)
| | - Dan Chen
- Jazz PharmaceuticalsPalo AltoCAUSA
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16
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Huang Z, Tang X, Zhang T, Qiu S, Xia Z, Fu P. Prevalence of sleep apnoea in non‐dialysis chronic kidney disease patients: A systematic review and meta‐analysis. Nephrology (Carlton) 2019; 24:1041-1049. [PMID: 30525256 DOI: 10.1111/nep.13546] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/03/2018] [Indexed: 02/05/2023]
Affiliation(s)
- Zhuo Huang
- Division of NephrologyKidney Research Institute, West China Hospital of Sichuan University Chengdu China
| | - Xi Tang
- Division of NephrologyKidney Research Institute, West China Hospital of Sichuan University Chengdu China
| | - Tao Zhang
- West China School of Public HealthSichuan University Chengdu China
| | - Shi Qiu
- Department of Urology, Institute of UrologyWest China Hospital of Sichuan University Chengdu China
| | - Zijing Xia
- Division of NephrologyKidney Research Institute, West China Hospital of Sichuan University Chengdu China
| | - Ping Fu
- Division of NephrologyKidney Research Institute, West China Hospital of Sichuan University Chengdu China
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17
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Rimke AN, Ahmed SB, Turin TC, Pendharkar SR, Raneri JK, Lynch EJ, Hanly PJ. Effect of CPAP therapy on kidney function in patients with obstructive sleep apnoea and chronic kidney disease: a protocol for a randomised controlled clinical trial. BMJ Open 2019; 9:e024632. [PMID: 30904853 PMCID: PMC6475212 DOI: 10.1136/bmjopen-2018-024632] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2018] [Revised: 01/04/2019] [Accepted: 02/13/2019] [Indexed: 12/21/2022] Open
Abstract
INTRODUCTION Obstructive sleep apnoea (OSA) is common in patients with chronic kidney disease (CKD) and may contribute to the progression of kidney disease either through direct effects of hypoxia on the kidney or indirectly through hypoxaemia-induced oxidative stress, endothelial dysfunction, inflammation, activation of the renin-angiotensin and sympathetic nervous systems, and hypertension. Treatment of OSA with continuous positive airway pressure (CPAP) improves many of these physiological abnormalities in patients with normal renal function, though to date there are no trials evaluating the effect of OSA treatment on kidney function in patients with CKD. The purpose of this study is to test the feasibility and efficacy of CPAP therapy in CKD patients with OSA. METHODS AND ANALYSIS The study is a randomised, controlled, non-blinded, parallel clinical trial in which patients with established CKD are screened for OSA. Patients with OSA are randomised to either conventional medical therapy (control group) or medical therapy and CPAP (CPAP group) and followed for 1 year. The primary outcome is the change in estimated glomerular filtration rate. Secondary outcomes are the change in the urinary albumin/creatinine ratio, the Epworth Sleepiness Scale , Pittsburgh Sleep Quality Index and Kidney Disease Quality of Life questionnaire. ETHICS AND DISSEMINATION Ethics approval has been obtained from the Conjoint Health Research Ethics Board (ID: REB15-0055). Results from this study will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT02420184; Pre-results.
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Affiliation(s)
| | | | | | | | | | | | - Patrick J Hanly
- Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Sleep Centre, Foothills Medical Centre, Calgary, Alberta, Canada
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18
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Song J, Wang C, Ma A, Zheng H, Zheng W, Hou X, Hu C, Chen L, Jia W. Self-reported snoring is associated with chronic kidney disease independent of metabolic syndrome in middle-aged and elderly Chinese. J Diabetes Investig 2019; 10:124-130. [PMID: 29694704 PMCID: PMC6319474 DOI: 10.1111/jdi.12855] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 04/13/2018] [Accepted: 04/17/2018] [Indexed: 11/29/2022] Open
Abstract
AIMS/INTRODUCTION To investigate the correlation between snoring and chronic kidney disease (CKD), and explore whether metabolic syndrome (MetS) plays an important role in this relationship among middle-aged and elderly Chinese. MATERIALS AND METHODS The participants included in the present study were categorized into three subgroups based on self-reported snoring frequency (regularly [≥3 times per week], occasionally [between 'regularly' and 'never'] or never [<1 time per month]). An estimated glomerular filtration rate <60 mL/min/1.73 m2 was considered as CKD. We diagnosed MetS based on the 2004 Chinese Diabetes Society criteria. We explored the relationship between snoring and CKD by using multiple logistic regressions. RESULTS The frequency of MetS, MetS components and CKD was dramatically higher in regular snorers than in non-snorers and occasional snorers. The odds ratios for MetS and all the MetS elements, except for hyperglycemia, increased progressively with the snoring frequency (P < 0.001). Upon additional adjustment for other MetS components, snoring was not significantly related with hypertension; however, the associations between snoring frequency and overweight/obesity and dyslipidemia became attenuated, but still remained statistically significant (P < 0.01). Interestingly, odds ratios for CKD also increasingly augmented with snoring frequency (P < 0.001). Upon further adjustment for individual MetS components or MetS, regular snoring also resulted in a significantly increased odds ratio for CKD (odds ratio 1.72; P = 0.034) relative to non-snoring. CONCLUSIONS Self-reported snoring is closely associated with CKD independent of MetS among middle-aged and elderly Chinese.
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Affiliation(s)
- Jun Song
- Shanghai Diabetes InstituteShanghai Key Laboratory of DiabetesShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
- Department of EndocrinologyQilu Hospital of Shandong UniversityJinanShandongChina
| | - Chuan Wang
- Department of EndocrinologyQilu Hospital of Shandong UniversityJinanShandongChina
| | - Aixia Ma
- Department of EndocrinologyQilu Hospital of Shandong UniversityJinanShandongChina
| | - Huizhen Zheng
- Department of EndocrinologyQilu Hospital of Shandong UniversityJinanShandongChina
| | - Wenjian Zheng
- Department of GeriatricsQingdao Haici Medical Treatment GroupQingdaoShandongChina
| | - Xinguo Hou
- Department of EndocrinologyQilu Hospital of Shandong UniversityJinanShandongChina
| | - Cheng Hu
- Shanghai Diabetes InstituteShanghai Key Laboratory of DiabetesShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
| | - Li Chen
- Department of EndocrinologyQilu Hospital of Shandong UniversityJinanShandongChina
| | - Weiping Jia
- Shanghai Diabetes InstituteShanghai Key Laboratory of DiabetesShanghai Jiao Tong University Affiliated Sixth People's HospitalShanghaiChina
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19
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Zhang Y, Luo Y, Wang Y, Liu H, Yang Y, Wang Q. Effect of deubiquitinase USP8 on hypoxia/reoxygenation‑induced inflammation by deubiquitination of TAK1 in renal tubular epithelial cells. Int J Mol Med 2018; 42:3467-3476. [PMID: 30221684 DOI: 10.3892/ijmm.2018.3881] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 09/04/2018] [Indexed: 11/06/2022] Open
Abstract
Intermittent hypoxia/reoxygenation (IHR), characterized by repeated episodes of hypoxia interspersed with periods of reoxygenation, has been found to induce pro‑inflammatory cytokine production and is increasingly recognized as a major pathophysiological factor in various disease processes with distinct cell and molecular responses. The present study is the first, to the best of our knowledge, to investigate the effects of ubiquitin‑specific peptidase 8 (USP8) on IHR‑induced inflammation in renal tubular epithelial cells and examine the underlying mechanism. Following transfection of plasmids, HK‑2 and TCMK‑1 cells were incubated for eight cycles of IHR treatment including 3 h of hypoxic incubation followed by 3 h of normoxic culture. It was demonstrated that the expression of USP8 was decreased in IHR conditions but not in normoxic or continuous hypoxic conditions. In addition, IHR‑induced inflammation was suppressed in USP8‑overexpressinh renal tubular epithelial cells, and the silencing of USP8 markedly aggravated inflammation. Furthermore, it was found that the overexpression of USP8 inhibited the IHR‑induced activation of nuclear factor‑κB and it was demonstrated that USP8 interacted with transforming growth factor‑β‑activated kinase‑1 (TAK1) and deubiquitinated the K63‑linked ubiquitination of TAK1. Taken together, the results demonstrated the role of USP8 in IHR‑induced inflammation and suggested USP8 as a potential and specific therapeutic target for IHR‑related diseases.
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Affiliation(s)
- Yuwei Zhang
- Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Yingquan Luo
- Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Yina Wang
- Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Hong Liu
- Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Yu Yang
- Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
| | - Qiong Wang
- Department of Geriatrics, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China
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20
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Zhang Y, Su X, Zou F, Xu T, Pan P, Hu C. Toll-like receptor-4 deficiency alleviates chronic intermittent hypoxia-induced renal injury, inflammation, and fibrosis. Sleep Breath 2018; 23:503-513. [PMID: 30099700 DOI: 10.1007/s11325-018-1704-9] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2018] [Revised: 07/16/2018] [Accepted: 07/30/2018] [Indexed: 02/03/2023]
Abstract
BACKGROUND Obstructive sleep apnea (OSA)-associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH) triggered renal damage. This study aims to investigate the role of toll-like receptor-4 (TLR4) in underlying mechanism involved chronic intermittent hypoxia (CIH)-induced renal damage. METHODS C57BL/6J mice with normal TLR4 (TLR4 WT) or deficient TLR4 (TLR4 KO) were divided into four groups and exposed to normal air (NA) and CIH: TLR4 WT + NA, TLR4 KO + NA, TLR4 WT + CIH, and TLR4 KO + CIH. CIH lasted for 8 h/day and 7 days/week for 6 weeks. Renal injury and inflammation were evaluated by histology and ELISA. Renal tubular apoptosis, macrophages, and fibroblasts recruitment were determined by TUNEL assay, immunofluorescence, and western blot. RESULTS In response to CIH, TLR4 deficiency alleviated renal histological injury, renal dysfunction, and fibrosis. TLR4 deficiency ameliorated renal dysfunction (serum BUN and creatinine) and tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL, and western blot of apoptotic protein (caspase-3, c-caspase-3, and Bax/Bcl-2 ratio). Furthermore, we also found TLR4 deficiency abrogated CIH-induced macrophages (CD68) and fibroblasts (α-SMA) recruitment, further reducing expression of extra-cellular matrix protein (collagen I and collagen IV) and inflammatory cytokines release (IL-6, TNF-α, and MCP-1). Finally, we used immunohistochemistry to demonstrate that TLR4 deficiency attenuated increased expression of MyD88 and NF-kB p65 after CIH treatment. CONCLUSIONS Our data suggest that TLR4 plays a vital role in CIH-induced renal injury, inflammation and fibrosis, and inhibition of TLR4 probably provides a therapeutic potential for CIH-induced kidney damage.
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Affiliation(s)
- Yan Zhang
- Department of Respiratory Medicine, Xiangya Hospital, Key Cite of National Clinical Research Center for Respiratory Disease, Central South University, Changsha, 410008, Hunan, People's Republic of China
| | - Xiaoli Su
- Department of Respiratory Medicine, Xiangya Hospital, Key Cite of National Clinical Research Center for Respiratory Disease, Central South University, Changsha, 410008, Hunan, People's Republic of China.
| | - Fangfang Zou
- Department of Respiratory Medicine, Xiangya Hospital, Key Cite of National Clinical Research Center for Respiratory Disease, Central South University, Changsha, 410008, Hunan, People's Republic of China
| | - Tengjuan Xu
- Department of Respiratory Medicine, Xiangya Hospital, Key Cite of National Clinical Research Center for Respiratory Disease, Central South University, Changsha, 410008, Hunan, People's Republic of China
| | - Pinhua Pan
- Department of Respiratory Medicine, Xiangya Hospital, Key Cite of National Clinical Research Center for Respiratory Disease, Central South University, Changsha, 410008, Hunan, People's Republic of China
| | - Chengping Hu
- Department of Respiratory Medicine, Xiangya Hospital, Key Cite of National Clinical Research Center for Respiratory Disease, Central South University, Changsha, 410008, Hunan, People's Republic of China
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21
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Voulgaris A, Archontogeorgis K, Nena E, Tsigalou C, Xanthoudaki M, Kouratzi M, Tripsianis G, Froudarakis M, Steiropoulos P. Serum levels of NGAL and cystatin C as markers of early kidney dysfunction in patients with obstructive sleep apnea syndrome. Sleep Breath 2018; 23:161-169. [PMID: 29946947 DOI: 10.1007/s11325-018-1677-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2018] [Revised: 05/20/2018] [Accepted: 05/30/2018] [Indexed: 12/26/2022]
Abstract
PURPOSE Obstructive sleep apnea syndrome (OSAS) has been recently proposed as an independent risk factor for chronic kidney disease. Cystatin C (Cyst C) and neutrophil gelatinase-associated lipocalin (NGAL) are novel biomarkers for the earlier detection of latent kidney disease. The aim of the study was to assess serum Cyst C and NGAL levels in otherwise healthy OSAS patients and to explore possible associations with sleep parameters. METHODS Consecutive subjects (n = 96, 79.2% males), without known comorbidities, with symptoms suggestive of OSAS were included. All of them underwent polysomnography (PSG) and blood examination for the measurement of serum Cyst C and NGAL levels. RESULTS Based on apnea-hypopnea index (AHI), subjects were classified into two groups: 32 controls and 64 OSAS patients, with no significant differences in terms of age (50.1 ± 11.7 vs 51 ± 12.2 years, p = 0.747) and BMI (33.9 ± 8.8 vs 35.9 ± 13.1 kg/m2, p = 0.449). Serum Cyst C and NGAL mean levels were higher in OSAS patients compared to those in controls (1155.2 ± 319.3 vs 966.8 ± 173 ng/ml, p = 0.001, and 43.7 ± 23.2 vs 35.6 ± 13.8 ng/ml, p = 0.035, respectively). After adjustment for age and BMI in OSAS patients, serum NGAL levels were associated with AHI (β = 0.341, p = 0.015) and minimum oxyhemoglobin saturation during sleep (β = - 0.275, p = 0.032), while serum Cyst C levels were associated with percentage of time with oxyhemoglobin saturation < 90% (β = 0.270, p = 0.043), average (β = - 0.308, p = 0.018), and minimum (β = - 0.410, p = 0.001) oxyhemoglobin saturation during sleep. CONCLUSIONS Higher risk for latent kidney disease in otherwise healthy OSAS patients is indicated. Sleep hypoxia seems to be a significant contributor in the pathogenetic process of renal dysfunction in OSAS.
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Affiliation(s)
- Athanasios Voulgaris
- MSc Programme in Sleep Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.,Department of Pneumonology, Medical School, Democritus University of Thrace and University General Hospital, Alexandroupolis, Greece
| | - Kostas Archontogeorgis
- MSc Programme in Sleep Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Evangelia Nena
- MSc Programme in Sleep Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.,Laboratory of Hygiene and Environmental Protection, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Christina Tsigalou
- Laboratory of Microbiology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Maria Xanthoudaki
- Department of Pneumonology, Medical School, Democritus University of Thrace and University General Hospital, Alexandroupolis, Greece
| | - Maria Kouratzi
- Department of Pneumonology, Medical School, Democritus University of Thrace and University General Hospital, Alexandroupolis, Greece
| | - Grigorios Tripsianis
- Laboratory of Medical Statistics, Medical School, Democritus University of Thrace, Alexandroupolis, Greece
| | - Marios Froudarakis
- Department of Pneumonology, Medical School, Democritus University of Thrace and University General Hospital, Alexandroupolis, Greece
| | - Paschalis Steiropoulos
- MSc Programme in Sleep Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. .,Department of Pneumonology, Medical School, Democritus University of Thrace and University General Hospital, Alexandroupolis, Greece.
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22
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Marrone O, Bonsignore MR. Obstructive sleep apnea and chronic kidney disease: open questions on a potential public health problem. J Thorac Dis 2018; 10:45-48. [PMID: 29600018 DOI: 10.21037/jtd.2017.12.12] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Oreste Marrone
- Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Palermo, Italy
| | - Maria R Bonsignore
- Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council (CNR), Palermo, Italy.,Biomedical Department of Internal and Specialistic Medicine (DiBiMIS), University of Palermo, Palermo, Italy
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23
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Chu G, Choi P, McDonald VM. Sleep disturbance and sleep-disordered breathing in hemodialysis patients. Semin Dial 2017; 31:48-58. [DOI: 10.1111/sdi.12617] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Affiliation(s)
- Ginger Chu
- Nephrology Department; Medical & Interventional Services; John Hunter Hospital; Hunter New England Local Health District NSW Australia
- School of Nursing and Midwifery; University of Newcastle; Newcastle NSW Australia
| | - Peter Choi
- Nephrology Department; Medical & Interventional Services; John Hunter Hospital; Hunter New England Local Health District NSW Australia
| | - Vanessa M. McDonald
- School of Nursing and Midwifery; University of Newcastle; Newcastle NSW Australia
- Priority Research Centre for Healthy Lung; School of Nursing and Midwifery; University of Newcastle; Newcastle NSW Australia
- Department of Respiratory and Sleep Medicine; John Hunter Hospital; Hunter New England Local Health District NSW Australia
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24
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Aziz F, Chaudhary K. The Triad of Sleep Apnea, Hypertension, and Chronic Kidney Disease: A Spectrum of Common Pathology. Cardiorenal Med 2016; 7:74-82. [PMID: 27994605 DOI: 10.1159/000450796] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Accepted: 09/05/2016] [Indexed: 01/07/2023] Open
Abstract
Obstructive sleep apnea (OSA), hypertension, and chronic kidney disease (CKD) are different entities and are generally managed individually most of the time. However, CKD, OSA, and hypertension share many common risk factors and it is not uncommon to see this complex triad together. In fact, they share similar pathophysiology and have been interlinked with each other. The common pathophysiology includes chronic volume overload, hyperaldosteronism, increased sympathetic activity, endothelial dysfunction, and increased inflammatory markers. The combination of this triad has significant negative impact on the cardiovascular health, and increases the mortality and morbidity in this complicated group of patients. On one hand, progression of CKD can lead to the worsening of OSA and hypertension; similarly, worsening sleep apnea can make the hypertension difficult to treat and enhance the progression of CKD. This review article highlights the bidirectional interlink among these apparently different disease processes which share common pathophysiological mechanisms and emphasizes the importance of treating them collectively to improve outcomes.
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Affiliation(s)
- Fahad Aziz
- Division of Nephrology, University of Missouri Health Science Center, Columbia, MO, USA
| | - Kunal Chaudhary
- Division of Nephrology, University of Missouri Health Science Center, Columbia, MO, USA; Nephrology Section, Harry S. Truman Veterans' Hospital, Columbia, MO, USA
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Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:1015390. [PMID: 27688824 PMCID: PMC5027322 DOI: 10.1155/2016/1015390] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Revised: 07/12/2016] [Accepted: 07/25/2016] [Indexed: 01/11/2023]
Abstract
Obstructive sleep apnea (OSA) associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH) triggered tissue damage. Receptor for advanced glycation end product (RAGE) and its ligand high mobility group box 1 (HMGB1) are expressed on renal cells and mediate inflammatory responses in OSA-related diseases. To determine their roles in CIH-induced renal injury, soluble RAGE (sRAGE), the RAGE neutralizing antibody, was intravenously administered in a CIH model. We also evaluated the effect of sRAGE on inflammation and apoptosis. Rats were divided into four groups: (1) normal air (NA), (2) CIH, (3) CIH+sRAGE, and (4) NA+sRAGE. Our results showed that CIH accelerated renal histological injury and upregulated RAGE-HMGB1 levels involving inflammatory (NF-κB, TNF-α, and IL-6), apoptotic (Bcl-2/Bax), and mitogen-activated protein kinases (phosphorylation of P38, ERK, and JNK) signal transduction pathways, which were abolished by sRAGE but p-ERK. Furthermore, sRAGE ameliorated renal dysfunction by attenuating tubular endothelial apoptosis determined by immunofluorescence staining of CD31 and TUNEL. These findings suggested that RAGE-HMGB1 activated chronic inflammatory transduction cascades that contributed to the pathogenesis of the CIH-induced renal injury. Inhibition of RAGE ligand interaction by sRAGE provided a therapeutic potential for CIH-induced renal injury, inflammation, and apoptosis through P38 and JNK pathways.
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Abstract
In end-stage renal disease (ESRD) and heart failure, conditions characterized by fluid overload, both obstructive sleep apnea (OSA) and central sleep apnea (CSA) are highly prevalent. This observation suggests that fluid overload may be a unifying mechanism in the pathogenesis of both OSA and CSA in these conditions. An overnight rostral fluid shift from the legs to the neck and lungs has been shown to contribute to the pathogenesis of OSA and CSA, respectively, in various different patient populations. This article reviews the evidence that supports a role for fluid overload and overnight fluid shift in the pathogenesis of sleep apnea in ESRD. The diagnosis, epidemiology, and clinical features of sleep apnea in patients with ESRD also are considered.
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Affiliation(s)
- Owen D Lyons
- Sleep Research Laboratory of the University Health Network Toronto Rehabilitation Institute, Toronto, Ontario, Canada; Centre for Sleep Medicine and Circadian Biology, University of Toronto, Toronto, Ontario, Canada.
| | - T Douglas Bradley
- Sleep Research Laboratory of the University Health Network Toronto Rehabilitation Institute, Toronto, Ontario, Canada; Centre for Sleep Medicine and Circadian Biology, University of Toronto, Toronto, Ontario, Canada; Division of Respirology, University of Toronto, Toronto, Ontario, Canada
| | - Christopher T Chan
- Division of Nephrology, Department of Medicine, University Health Network, Toronto General Hospital, Toronto, Ontario, Canada
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Abstract
Sleep is an essential function of life and serves a crucial role in the promotion of health and performance. Poor sleep quality and sleep disorders have been a recurrent finding in patients with chronic kidney disease (CKD). Sleep disorders such as obstructive sleep apnea (OSA) can contribute to hypertension, diabetes, cardiovascular disease, and worsen obesity, all of which are implicated in the etiology of CKD, but CKD itself may lead to OSA. Relationships between CKD/end-stage renal disease (ESRD) and OSA have been the subject of numerous investigations, but central sleep apnea (CSA) also is highly prevalent in CKD/ESRD but remains poorly understood, underdiagnosed, and undertreated in these patients. Emerging literature has implicated CSA as another contributor to morbidity and mortality in CKD/ESRD, and several studies have suggested that CSA treatment is beneficial in improving these outcomes. Patients with CKD/ESRD co-existing with congestive heart failure are particularly prone to CSA, and studies focused on managing CSA in congestive heart failure patients have provided important information concerning how best to manage CSA in kidney disease as well. Adaptive servo-ventilation ultimately may represent the treatment of choice in these patients, although a stepped approach using a variety of therapeutic modalities is recommended.
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Affiliation(s)
- Sushma M Dharia
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM
| | - Mark L Unruh
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM
| | - Lee K Brown
- Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM.
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Chan GC, Lam B, Yap DY, Ip MS, Lai KN, Tang SC. Proteinuria is associated with sleep apnea in chronic kidney disease. Nephrol Dial Transplant 2016; 31:772-779. [DOI: 10.1093/ndt/gfv306] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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Abstract
PURPOSE OF REVIEW Obstructive sleep apnea (OSA) has been shown to be an independent risk factor for the development and progression of diabetes mellitus. Interestingly, there is also a strong correlation between OSA and the development and progression of chronic kidney disease (CKD). As diabetes mellitus is the most common cause of CKD, in this review we summarize the current literature regarding this interconnecting relationship between OSA, CKD, and diabetes mellitus. The literature increasingly supports a bidirectional relationship between CKD and OSA among diabetes mellitus patients leading to an increased rate of progression of diabetic nephropathy. RECENT FINDINGS There is growing evidence that among patients with diabetes mellitus, OSA may be a strong risk factor for the development of diabetic nephropathy. The treatment of OSA in CKD patients may play a role in attenuating the rate of the progression of CKD. SUMMARY Clinicians should have a low threshold for evaluating diabetic patients with CKD for OSA. Further studies examining if treatment of OSA would improve the outcomes of CKD patients in general and diabetic CKD patients in particular are needed.
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Meyring-Wösten A, Zhang H, Ye X, Fuertinger DH, Chan L, Kappel F, Artemyev M, Ginsberg N, Wang Y, Thijssen S, Kotanko P. Intradialytic Hypoxemia and Clinical Outcomes in Patients on Hemodialysis. Clin J Am Soc Nephrol 2016; 11:616-25. [PMID: 26936946 DOI: 10.2215/cjn.08510815] [Citation(s) in RCA: 48] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Accepted: 12/21/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND OBJECTIVES Intradialytic hypoxemia has been recognized for decades, but its associations with outcomes have not yet been assessed in a large patient cohort. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Our retrospective cohort study was conducted between January of 2012 and January of 2015. We recorded blood oxygen saturation every minute during hemodialysis in patients with arteriovenous access. A 6-month baseline period with at least 10 treatments with oxygen saturation measurements preceded a 12-month follow-up. Patients were stratified by the presence or absence of prolonged intradialytic hypoxemia defined as oxygen saturation <90% for at least one third of the treatment time. Demographic, laboratory, and treatment data and hospitalization and mortality rates were compared between the groups. Multivariate Cox regression analysis was used to assess baseline predictors of all-cause mortality during follow-up. RESULTS In total, 100 (10%) of 983 patients had prolonged intradialytic hypoxemia. These patients were older (+3.6 years; 95% confidence interval, 0.8 to 6.3), had longer dialysis vintage (+1.2 years; 95% confidence interval, 0.3 to 2.1), and had higher prevalence of congestive heart failure (+10.8%; 95% confidence interval, 1.6 to 20.7) and chronic obstructive pulmonary disease (+13%; 95% confidence interval, 5 to 21.2). They also resembled an inflammatory phenotype, with lower serum albumin levels (-0.1 g/dl; 95% confidence interval, -0.2 to 0) and higher neutrophil-to-lymphocyte ratios (+1; 95% confidence interval, 0.5 to 1.6). They had lower hemoglobin levels (-0.2 g/dl; 95% confidence interval, -0.4 to 0) and required more erythropoietin (+1374 U per hemodialysis treatment; 95% confidence interval, 343 to 2405). During follow-up, all-cause hospitalization (1113 hospitalizations; univariate hazard ratio, 1.46; 95% confidence interval, 1.22 to 1.73) and mortality (89 deaths; adjusted hazard ratio, 1.98; 95% confidence interval, 1.14 to 3.43) were higher in patients with prolonged intradialytic hypoxemia. CONCLUSIONS Prolonged intradialytic hypoxemia was associated with laboratory indicators of inflammation, higher erythropoietin requirements, and higher all-cause hospitalization and mortality.
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Affiliation(s)
| | | | - Xiaoling Ye
- Renal Research Institute, New York, New York
| | | | - Lili Chan
- Icahn School of Medicine at Mount Sinai, New York, New York
| | - Franz Kappel
- Institute for Mathematics and Scientific Computing, University Graz, Graz, Austria; and
| | | | | | - Yuedong Wang
- Department of Statistics and Applied Probability, University of California, Santa Barbara, California
| | | | - Peter Kotanko
- Renal Research Institute, New York, New York; Icahn School of Medicine at Mount Sinai, New York, New York;
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Hanly PJ. Consider the Kidney when Managing Obstructive Sleep Apnea. J Clin Sleep Med 2015; 11:845-6. [PMID: 26094917 DOI: 10.5664/jcsm.4928] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2015] [Accepted: 03/18/2015] [Indexed: 11/13/2022]
Affiliation(s)
- Patrick J Hanly
- Health Sciences Centre, University of Calgary, Calgary, Canada
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Prevalence and Diagnostic Approach to Sleep Apnea in Hemodialysis Patients: A Population Study. BIOMED RESEARCH INTERNATIONAL 2015; 2015:103686. [PMID: 26229952 PMCID: PMC4502277 DOI: 10.1155/2015/103686] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Accepted: 06/16/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND Previous observations found a high prevalence of obstructive sleep apnea (OSA) in the hemodialysis population, but the best diagnostic approach remains undefined. We assessed OSA prevalence and performance of available screening tools to propose a specific diagnostic algorithm. METHODS 104 patients from 6 Swiss hemodialysis centers underwent polygraphy and completed 3 OSA screening scores: STOP-BANG, Berlin's Questionnaire, and Adjusted Neck Circumference. The OSA predictors were identified on a derivation population and used to develop the diagnostic algorithm, which was validated on an independent population. RESULTS We found 56% OSA prevalence (AHI ≥ 15/h), which was largely underdiagnosed. Screening scores showed poor performance for OSA screening (ROC areas 0.538 [SE 0.093] to 0.655 [SE 0.083]). Age, neck circumference, and time on renal replacement therapy were the best predictors of OSA and were used to develop a screening algorithm, with higher discriminatory performance than classical screening tools (ROC area 0.831 [0.066]). CONCLUSIONS Our study confirms the high OSA prevalence and highlights the low diagnosis rate of this treatable cardiovascular risk factor in the hemodialysis population. Considering the poor performance of OSA screening tools, we propose and validate a specific algorithm to identify hemodialysis patients at risk for OSA for whom further sleep investigations should be considered.
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Renal functions in obstructive sleep apnea patients. Sleep Breath 2015; 20:191-5. [DOI: 10.1007/s11325-015-1204-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Revised: 04/09/2015] [Accepted: 05/25/2015] [Indexed: 10/23/2022]
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Obstructive sleep apnea syndrome: An important piece in the puzzle of cardiovascular risk factors. CLINICA E INVESTIGACION EN ARTERIOSCLEROSIS 2014; 27:256-63. [PMID: 25496654 DOI: 10.1016/j.arteri.2014.10.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 09/30/2014] [Accepted: 10/01/2014] [Indexed: 11/20/2022]
Abstract
The obstructive sleep apnea syndrome (OSA) is a clinical entity characterized by recurring episodes of apnea and/or hypopnea during sleep, due to a total or partial collapse, respectively, of the upper airway. This collapse originates a set of pathophysiological changes that determine the appearance of several cardiovascular complications. OSA contributes for the development of hypertension, heart failure, arrhythmias and coronary heart disease. Nowadays it is recognized to be an important public health problem, taking into account not just its repercussions but also its prevalence, since the main risk factor for the disease is obesity, a growing problem worldwide, both in developed and developing countries. The present review summarizes the current knowledge about OSA, as regards its definition, pathophysiology, clinical manifestations, diagnosis, cardiovascular effects and treatment.
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Hanly PJ, Ahmed SB. Sleep apnea and the kidney: is sleep apnea a risk factor for chronic kidney disease? Chest 2014; 146:1114-1122. [PMID: 25288001 DOI: 10.1378/chest.14-0596] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
The prevalence of chronic kidney disease (CKD) is increasing, which presents challenges for both patients and health-care budgets. Although this phenomenon has been attributed to the growth in diabetes, hypertension, and obesity, sleep apnea and nocturnal hypoxemia may also contribute to the pathogenesis of CKD and its progression to kidney failure. Two pathophysiologic mechanisms responsible for CKD are glomerular hyperfiltration and chronic intrarenal hypoxia, resulting in tubulointerstitial injury, the final common pathway to end-stage kidney disease (ESKD). Multiple descriptive studies have demonstrated an association between CKD and sleep apnea. Although sleep apnea is common in patients with CKD and associated with significant nocturnal hypoxemia, it is often relatively free of sleep-related symptoms, making it difficult to detect without objective nocturnal monitoring. Nevertheless, sleep apnea and nocturnal hypoxemia have been associated with loss of kidney function and kidney injury, suggesting that they contribute to the pathogenesis of continued deterioration in kidney function. There are several pathways through which sleep apnea may achieve this, including a direct effect of intrarenal hypoxia and activation of the systemic and renal renin-angiotensin system. Further research is required to better understand these relationships and determine whether specific interventions in patients with sleep apnea have an impact on clinical outcomes, such as reducing the prevalence of CKD and delaying its progression to ESKD.
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Affiliation(s)
- Patrick J Hanly
- Division of Respiratory Medicine, Sleep Centre, Foothills Medical Centre.
| | - Sofia B Ahmed
- Division of Nephrology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada
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Predictors of successful completion of diagnostic home sleep testing in patients with chronic kidney disease. Sleep Breath 2014; 19:669-75. [PMID: 25369789 DOI: 10.1007/s11325-014-1074-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2014] [Revised: 10/17/2014] [Accepted: 10/23/2014] [Indexed: 10/24/2022]
Abstract
PURPOSE Obstructive sleep apnea (OSA) is common among patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Home sleep testing is used to diagnose OSA in many studies investigating sleep-disordered breathing in this population. However, failure to successfully complete the test is a significant source of participant exclusion from research studies and delayed diagnosis in clinical practice. The objective of the study was to identify potential factors impeding acceptance and successful completion of home sleep testing in patients with kidney disease. METHODS Four hundred and nineteen patients were recruited from nephrology clinics and dialysis units. Following completion of a sleep and medical history questionnaire, all patients were invited to perform a single night, home sleep study. Acceptance or refusal of the test was noted, as well as the success of the sleep study, as determined by a review of the raw data by a sleep medicine physician. RESULTS Male gender (OR = 1.61, CI = 1.02-2.53), hypertension (OR = 2.01, CI = 1.17-3.45), and snoring (OR = 1.75, CI = 1.11-2.77) were associated with sleep test acceptance. Older patients were less likely to accept the test (OR = 0.48, CI = 0.30-0.76). Diabetics were less likely to complete the sleep test successfully (OR = 0.28, CI = 0.12-0.66). CONCLUSIONS Advanced age is an important factor in test refusal and complications of diabetes contributes to test failure. Symptom matching may be a source of selection bias, as patients with risk factors for OSA are more likely to accept the diagnostic test.
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Estimating glomerular filtration rate in older people. BIOMED RESEARCH INTERNATIONAL 2014; 2014:916542. [PMID: 24772439 PMCID: PMC3977451 DOI: 10.1155/2014/916542] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Accepted: 02/15/2014] [Indexed: 12/23/2022]
Abstract
We aimed at reviewing age-related changes in kidney structure and function, methods for estimating kidney function, and impact of reduced kidney function on geriatric outcomes, as well as the reliability and applicability of equations for estimating glomerular filtration rate (eGFR) in older patients. CKD is associated with different comorbidities and adverse outcomes such as disability and premature death in older populations. Creatinine clearance and other methods for estimating kidney function are not easy to apply in older subjects. Thus, an accurate and reliable method for calculating eGFR would be highly desirable for early detection and management of CKD in this vulnerable population. Equations based on serum creatinine, age, race, and gender have been widely used. However, these equations have their own limitations, and no equation seems better than the other ones in older people. New equations specifically developed for use in older populations, especially those based on serum cystatin C, hold promises. However, further studies are needed to definitely accept them as the reference method to estimate kidney function in older patients in the clinical setting.
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Nicholl DDM, Ahmed SB, Loewen AHS, Hemmelgarn BR, Sola DY, Beecroft JM, Turin TC, Hanly PJ. Diagnostic value of screening instruments for identifying obstructive sleep apnea in kidney failure. J Clin Sleep Med 2013; 9:31-8. [PMID: 23319902 DOI: 10.5664/jcsm.2334] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) have a high prevalence of obstructive sleep apnea (OSA) that can have significant clinical implications. An accurate clinical screening tool for OSA that identifies patients for further diagnostic testing would assist in the identification of this comorbidity. The Berlin Questionnaire (BQ), Adjusted Neck Circumference (ANC), and STOP-BANG questionnaire are 3 such instruments that have been validated in patients with normal kidney function. OBJECTIVE The objective of this study was to determine the validity of these screening instruments in patients with CKD and ESRD, using overnight cardiopulmonary monitoring to diagnose OSA. METHODS One hundred seventy-two patients were recruited from nephrology clinics and hemodialysis units (CKD: n = 109; ESRD: n = 63). All patients completed the BQ, ANC, STOP-BANG, and overnight cardiopulmonary monitoring to diagnose OSA (respiratory disturbance index [RDI] ≥ 15). Sensitivity, specificity, positive and negative predictive values, and accuracy were calculated for the BQ, ANC, and STOP-BANG. RESULTS Obstructive sleep apnea was present in 41 CKD patients (38%) and 32 ESRD patients (51%). All screening instruments had satisfactory sensitivity (56% to 94%) but poor specificity (29% to 77%) and low accuracy (51% to 69%) in both CKD and ESRD patients with RDI ≥ 15. Using an RDI ≥ 30 yielded similar results. CONCLUSIONS Current screening questionnaires do not accurately identify patients at high risk for OSA or rule out the presence of OSA in patients with CKD and ESRD. Consequently, objective monitoring during sleep is required to reliably identify sleep apnea in these patient populations.
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