0
Original Research: SLEEP DISORDERS |

Declining Kidney Function Increases the Prevalence of Sleep Apnea and Nocturnal HypoxiaSleep Apnea and Chronic Kidney Disease FREE TO VIEW

David D. M. Nicholl, BHSc; Sofia B. Ahmed, MD; Andrea H. S. Loewen, MD; Brenda R. Hemmelgarn, MD, PhD; Darlene Y. Sola, RN; Jaime M. Beecroft, MSc; Tanvir C. Turin, MBBS, PhD; Patrick J. Hanly, MD
Author and Funding Information

From the Department of Medicine (Mr Nicholl; Drs Ahmed, Loewen, Hemmelgarn, Turin, and Hanly; and Ms Sola), Faculty of Medicine, and Sleep Centre (Drs Loewen and Hanly and Mr Beecroft), Foothills Medical Centre, University of Calgary, Calgary, AB, Canada.

Correspondence to: Patrick J. Hanly, MD, 1421 Health Sciences Centre, 3330 Hospital Dr NW, Calgary, AB, T2N 4Z5, Canada; e-mail: phanly@ucalgary.ca


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

Funding/Support: This research was supported by the Alberta Heritage Foundation for Medical Research, O’Brien Centre, University of Calgary, and the Department of Medicine, University of Calgary.


© 2012 American College of Chest Physicians


Chest. 2012;141(6):1422-1430. doi:10.1378/chest.11-1809
Text Size: A A A
Published online

Background:  Sleep apnea is an important comorbidity in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Although the increased prevalence of sleep apnea in patients with ESRD is well established, few studies have investigated the prevalence of sleep apnea in patients with nondialysis-dependent kidney disease, and no single study, to our knowledge, has examined the full spectrum of kidney function. We sought to determine the prevalence of sleep apnea and associated nocturnal hypoxia in patients with CKD and ESRD. We hypothesized that the prevalence of sleep apnea would increase progressively as kidney function declines.

Methods:  Two hundred fifty-four patients were recruited from outpatient nephrology clinics and hemodialysis units. All patients completed an overnight cardiopulmonary monitoring test to determine the prevalence of sleep apnea (respiratory disturbance index ≥ 15) and nocturnal hypoxia (oxygen saturation < 90% for ≥ 12% of monitoring). Patients were stratified into three groups based on estimated glomerular filtration rate (eGFR) as follows: eGFR ≥ 60 mL/min/1.73 m2 (n = 55), CKD (eGFR < 60 mL/min/1.73 m2 not on dialysis, n = 124), and ESRD (on hemodialysis, n = 75).

Results:  The prevalence of sleep apnea increased as eGFR declined (eGFR ≥ 60 mL/min/1.73 m2, 27%; CKD, 41%; ESRD, 57%; P = .002). The prevalence of nocturnal hypoxia was higher in patients with CKD and ESRD (eGFR ≥ 60 mL/min/1.73 m2, 16%; CKD, 47%; ESRD, 48%; P < .001).

Conclusions:  Sleep apnea is common in patients with CKD and increases as kidney function declines. Almost 50% of patients with CKD and ESRD experience nocturnal hypoxia, which may contribute to loss of kidney function and increased cardiovascular risk.

Figures in this Article

Sleep apnea occurs in > 50% of patients with end-stage renal disease (ESRD),16 which is considerably higher than in the general population.7 In contrast to the extensive ESRD literature, few studies have investigated the prevalence of sleep apnea in patients with nondialysis-dependent chronic kidney disease (CKD). These studies have been limited by small sample size, selective recruitment, lack of appropriate comparison groups, and equivocal definitions of sleep apnea and CKD, and no single study, to our knowledge, has evaluated patients with the full spectrum of kidney function.812

The coexistence of sleep apnea in patients with CKD and ESRD is likely to have clinical relevance. In addition to impairment of sleep quality and daytime function,13 sleep apnea increases the risk of hypertension,14 atherosclerosis,15 and vascular disease.1618 Vascular disorders are common to both patients with CKD and patients with ESRD, and their prevalence may be further increased by unrecognized sleep apnea.19 Further, sleep apnea is characteristically associated with nocturnal hypoxia, which is the main biologic mechanism through which these vascular complications develop.1923 It is also possible that sleep apnea accelerates the deterioration of kidney function in patients with CKD either indirectly by increasing systemic BP, inflammatory cytokines, and sympathetic nervous system activity24 (all of which have been proposed to reduce kidney function20,21,23) or directly through the effect of hypoxia on the kidney.25,26

We sought to determine, through a cross-sectional study design, the prevalence of sleep apnea and nocturnal hypoxia in patients with CKD and to confirm the reported high prevalence of sleep apnea in patients with ESRD. We hypothesized that patients with CKD and ESRD have an increased prevalence of sleep apnea, which increases as kidney function declines.

Patient Selection and Recruitment

Adult patients (aged ≥ 18 years) attending outpatient nephrology clinics and hemodialysis units were invited to participate in the study. Exclusion criteria included supplemental oxygen use, tracheostomy, and inability to give informed consent. The study was approved by the University of Calgary Conjoint Health Research Ethics Board (E#20091). Informed consent was obtained from all participants in accordance with the Declaration of Helsinki.

Patients were stratified according to their estimated glomerular filtration rate (eGFR) at the time of the study visit and classified into three groups based on the National Kidney Foundation staging system as follows: eGFR ≥ 60 mL/min/1.73 m2, CKD (eGFR < 60 mL/min/1.73 m2), and ESRD (on hemodialysis).27 eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.28

All patients completed a questionnaire that surveyed for demographic information; sleep and medical history, including hypertension, congestive heart failure, coronary artery disease (angina, myocardial infarction, and coronary artery bypass surgery), cerebrovascular disease (stroke or transient ischemic attack), diabetes, and COPD; and medication use. Medications included sedatives (benzodiazepines and hypnotics), antidepressants, and narcotics.

Sleep Apnea and Nocturnal Hypoxia

Patients performed an unattended, overnight cardiopulmonary monitoring study at home (Remmers Sleep Recorder Model 4.2; SagaTech Electronics Inc). Dialysis patients were asked to perform the overnight study on a dialysis-free day. The monitor consisted of an oximeter to record arterial oxygen saturation (Sao2) and heart rate variability, a pressure transducer to record nasal airflow, a microphone to record snoring, and a body position sensor. The oximeter provided the data for an automated scoring algorithm, which calculated the respiratory disturbance index (RDI) based on the number of episodes of oxyhemoglobin desaturation ≥ 4% per hour of monitoring. Nocturnal oxygen saturation was sampled at 1 Hz. The Remmers Sleep Recorder was validated by comparison with attended polysomnography.29,30 We defined sleep apnea as an RDI ≥ 15 because this reflects moderately severe sleep apnea that is likely to be clinically significant.31,32 The Remmers Sleep Recorder has a sensitivity of 98% and specificity of 88% for a designation criteria of RDI ≥ 15.30 A sleep medicine physician (P. J. H.) blinded to the patients’ kidney function reviewed the raw data, confirmed that the estimated RDI was accurate, and determined whether apnea was central (Cheyne-Stokes respiration [CSR]) or obstructive (obstructive sleep apnea [OSA]) based on the morphology of the airflow recordings. Nasal pressure recordings with a characteristic crescendo/decrescendo pattern and no evidence of airflow limitation were classified as CSR, whereas recordings without a crescendo/decrescendo pattern and with airflow limitation were classified as OSA (Fig 1). Nocturnal hypoxia was defined as an Sao2 < 90% for ≥ 12% of monitoring, which has previously been used in the Sleep Heart Health Study.33

Figure Jump LinkFigure 1. Nocturnal cardiopulmonary recording demonstrating Cheyne-Stokes respiration and obstructive sleep apnea. Each example is 10 min. HR = heart rate; NP = nasal pressure; SaO2 = arterial oxygen saturation.Grahic Jump Location

If the nocturnal cardiopulmonary monitoring test was nondiagnostic (patient did not sleep, unsatisfactory technical quality, or short monitoring time), the test was repeated. If the test remained nondiagnostic or was declined, it was classified as inconclusive, and the patient was excluded from further analysis. Patients with a previously completed sleep study, prior diagnosis of sleep apnea, or treatment with CPAP were included if their diagnostic sleep study was available for review and their eGFR was known at the time of the sleep study.

Statistical Analysis

Data are reported as mean ± SD for continuous variables and median (range) for categorical and nonnormally distributed variables. Parametric and nonparametric tests were used when appropriate. The unpaired t test or the Mann-Whitney U test was used for comparisons between two groups, whereas the one-way analysis of variance or the Kruskal-Wallis test was used for comparison among three groups. The Jonckheere-Terpstra test was used to examine trends among nonnormally distributed continuous variables. Categorical comparisons were analyzed using the χ2 test and Fisher exact test. Univariate and multivariate logistic regression models were used to identify the factors associated with sleep apnea and nocturnal hypoxia. Traditional risk factors for sleep apnea (age, male sex, BMI, neck circumference, history of cardiovascular disease, cerebrovascular disease, diabetes, sedatives, and antidepressants) and kidney function status (eGFR ≥ 60, CKD, ESRD) were included. For nocturnal hypoxia, COPD and RDI were added to these variables. The Hosmer-Lemeshow goodness-of-fit test and omnibus tests of model coefficients were used to test the model fit for the logistic regression models. These tests demonstrated that the models were sensitive to differences in kidney function groups and that there was an adequate fit of the data to the model. All statistical analyses were two sided with a .05 significance level and were performed using SPSS version 17.0 (SPSS Inc) software.

Patient Recruitment

A total of 403 patients (eGFR ≥ 60, n = 87; CKD, n = 185; ESRD, n = 132) were recruited (Fig 2); 149 did not complete overnight cardiopulmonary monitoring for the following reasons: anxiety, travel distance, lack of time (n = 122); technical difficulties (n = 22); and receiving treatment with CPAP (n = 5). Comparison of the remaining 254 patients (eGFR ≥ 60, n = 55; CKD, n = 124; ESRD, n = 75) (Table 1) with the 149 who withdrew showed that those who completed the study were younger men with hypertension and larger neck circumferences.

Figure Jump LinkFigure 2. Patient recruitment. PSG = polysomnography; RSR = Remmers Sleep Recorder.Grahic Jump Location
Table Graphic Jump Location
Table 1 —Clinical Profile of Patients Who Completed the Study Compared With Patients Who Withdrew From the Study

Data are presented as mean ± SD or No. (%), unless otherwise indicated. CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease.

Clinical Profile

Patients with CKD and ESRD were older than patients with eGFR ≥ 60 (Table 2). BMI also differed across groups. The prevalence of hypertension was > 50% in all patient groups and was significantly higher in those with CKD and ESRD. The prevalence of other comorbidities increased as eGFR declined. There was no difference in the prevalence of antidepressant medications, but sedatives and narcotics were used more frequently as kidney function declined. A history of snoring was reported equally across the three groups (eGFR ≥ 60, n = 35 [64%]; CKD, n = 93 [75%]; ESRD, n = 51 [68%]; χ2 = 2.677; P = .262). Unrefreshing sleep was also reported equally across the three groups (eGFR ≥ 60, n = 27 [49%]; CKD, n = 53 [43%]; ESRD, n = 47 [63%]; χ2 = 2.677; P = .407).

Table Graphic Jump Location
Table 2 —Clinical Profile of All Patients Who Completed the Study

Data are presented as mean ± SD, No. (%), or median (range), unless otherwise indicated. See Table 1 legend for expansion of abbreviations.

a 

CKD (eGFR < 60 mL/min/1.73 m).

b 

ESRD (on hemodialysis).

Sleep Apnea

The mean duration of nocturnal cardiopulmonary monitoring was 6.8 ± 1.5 h for patients with eGFR ≥ 60, 7.2 ± 1.5 h for patients with CKD, and 6.4 ± 2.0 h for patients with ESRD. Furthermore, the proportion of monitoring time that patients reported sleeping was 85.5% ± 12.5% for eGFR ≥ 60, 80.7% ± 14.9% for CKD, and 78.1% ± 17.8% for ESRD. Consequently, sleep efficiency and monitoring time were sufficiently long to capture important respiratory events (Fig 3, Table 3).

Figure Jump LinkFigure 3. Prevalence of sleep apnea in all patients. CKD = chronic kidney disease; CSR = Cheyne-Stokes respiration; eGFR ≥ 60 = estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2; ESRD = end-stage renal disease; OSA = obstructive sleep apnea; RDI = respiratory disturbance index.Grahic Jump Location
Table Graphic Jump Location
Table 3 —Prevalence of Sleep Apnea and Nocturnal Hypoxia in All Patients

Data are presented as median (range) or No.(%), unless otherwise indicated. RDI = respiratory disturbance index; Sao2 = arterial oxygen saturation; TTPO = total time oximeter probe was on the patient. See Table 1 legend for expansion of other abbreviations.

a 

CKD (eGFR < 60 mL/min/1.73 m).

b 

ESRD (on hemodialysis).

The proportion of patients with sleep apnea increased as kidney function decreased (eGFR ≥ 60, n = 15 [27%]; CKD, n = 51 [41%]; ESRD, n = 43 [57%]; χ2 = 12.019; P = .002). Sleep apnea was predominantly obstructive; however, the prevalence of CSR increased as eGFR decreased. The RDI was higher in groups with lower kidney function. Trend analysis indicated a significant increase in RDI as kidney function declined (P < .001).

Nocturnal Hypoxia

The proportion of patients who experienced nocturnal hypoxia increased as eGFR decreased (Fig 4). Nocturnal hypoxia was found in 9 patients (16%) with eGFR ≥ 60, 58 patients (47%) with CKD, and 36 patients (48%) with ESRD (χ2 = 17.328, P < .001) (Fig 4, Table 3). Trend analysis indicated a significant increase in the duration of Sao2 < 90% as kidney function declined (P = .004).

Figure Jump LinkFigure 4. Prevalence of nocturnal hypoxia in all patients. See Figure 1 and 3 legends for expansion of abbreviations.Grahic Jump Location
Regression Analysis

Univariate logistic regression for sleep apnea revealed that ESRD, advanced age, male sex, increased BMI, increased neck circumference, congestive heart failure, coronary artery disease, and diabetes were associated with sleep apnea (Table 4). Multivariate analysis revealed that ESRD, advanced age, increased BMI, and increased neck circumference were associated with sleep apnea (Nagelkerke R2, 0.400) (Table 4).

Table Graphic Jump Location
Table 4 —Univariate and Multivariate Analyses for Sleep Apnea and Nocturnal Hypoxia

See Table 1 and 3 legends for expansion of abbreviations.

a 

Sleep apnea RDI ≥ 15.

b 

Nocturnal hypoxia Sao2 < 90% for ≥ 12% of monitoring time.

Univariate analyses for nocturnal hypoxia revealed that CKD, ESRD, advanced age, increased BMI, increased neck circumference, congestive heart failure, coronary artery disease, cerebrovascular disease, diabetes, COPD, and RDI were significant predictors of nocturnal hypoxia (Table 4). Multivariate analysis indicated that CKD, COPD, and RDI were significant predictors of increased risk for nocturnal hypoxia, with RDI being the strongest (Nagelkerke R2, 0.480) (Table 4). ESRD, advanced age, and increased BMI were of borderline significance. Exclusion of the 14 patients who completed a polysomnography test instead of home cardiopulmonary monitoring did not alter the results.

We found that the prevalence and severity of sleep apnea increased as kidney function declined. Furthermore, sleep apnea is common in patients with CKD in addition to those with ESRD. We also found a high prevalence of nocturnal hypoxia in patients with CKD and ESRD that appeared to be due to both sleep apnea and additional nonapneic factors.

Previous studies have evaluated the prevalence of sleep apnea in CKD. Markou et al10 reported a 31.4% prevalence of sleep apnea in a cross-sectional study of 35 patients with CKD, but their study was limited by a small sample size and the absence of comparative groups with eGFR ≥ 60 and ESRD. Further, patients with cardiovascular disease were excluded, limiting the generalizability of their findings because cardiovascular comorbidities are common in this patient population.19,23 Sim et al12 reported an increased risk for sleep apnea in patients with mildly reduced eGFR. However, the prevalence of sleep apnea was low (2.5%), and the absence of BMI data precluded adjustment for the known association between obesity and sleep apnea.7,34 Canales et al8 reported an increased prevalence (27%) of sleep apnea in a cohort of elderly men but found no association with kidney function. Sakaguchi et al11 reported an increased prevalence (32%) of sleep apnea in 100 patients with CKD in Japan, which may not be generalizable to non-Asian populations. Roumelioti et al9 reported a high prevalence (22.5%) of severe sleep apnea in 89 patients with CKD but used historical control data where kidney function was undefined. Finally, in all of these studies, eGFR was determined using the Modification of Diet and Renal Disease Study equation, which is unreliable at eGFR ≥ 60, introducing potential misclassification bias.35,36

The present study addressed several of these limitations. First, we examined patients with the full spectrum of kidney function, ranging from those with eGFR ≥ 60 to ESRD. Second, all patients were recruited from nephrology clinics and hemodialysis units, including those with minimally impaired kidney function (eGFR > 60), which we believe is the most appropriate control group for this study. The high prevalence of sleep apnea in this group likely reflects the fact that the patients comprised a referred population with a high prevalence of hypertension and other renal symptoms. Third, patients were not excluded by age, sex, comorbidities, or medications, improving the generalizability of the findings to the CKD and ESRD populations. Comparison of the present ESRD population to a cohort of 237 patients with ESRD from the Southern Alberta Renal Program showed a similar clinical profile.37 The present CKD population also had a similar clinical profile to the Chronic Renal Insufficiency Cohort study.38 Consequently, we believe that the present study population is representative of the general CKD and ESRD populations. In addition, we determined eGFR using the CKD-EPI equation, which provides a more reliable classification of patients with an eGFR ≥ 60.28,36

Among traditional risk factors, advanced age, increased BMI, increased neck circumference, cardiovascular disease, and diabetes were all associated with sleep apnea. Additionally, kidney disease status was associated with sleep apnea. Multivariate analysis did not show any association between sleep apnea and comorbid vascular disease. These data imply that reduced kidney function may contribute to the pathogenesis of sleep apnea independently of traditional risk factors for sleep apnea and coexisting vascular disease. Both fluid overload39 and altered chemical control of breathing40,41 have been proposed to cause sleep apnea in patients with ESRD. It is possible that similar mechanisms contribute to the pathogenesis of sleep apnea in patients with CKD prior to starting dialysis.

A striking finding was the high prevalence of nocturnal hypoxia in patients with CKD that was similar to that seen in patients with ESRD. Furthermore, only a portion of the nocturnal hypoxia in the CKD and ESRD groups was attributed to sleep apnea, suggesting that the pathogenesis was partly due to nonapneic factors. Two possible mechanisms are comorbid pulmonary and cardiac disease and medications that can alter the mechanics and control of respiration.4043 Multivariate analysis revealed that COPD was associated with nocturnal hypoxia, but cardiovascular disease and use of sedatives and narcotics were not. Other potential causes, such as fluid overload, should be considered in future studies.

What are the clinical implications of the findings? Sleep apnea increases the risk of hypertension,14 cardiovascular disease, and cerebrovascular disease,16,18 all of which are important and highly prevalent complications of both CKD and ESRD.19,22,23,37,38 These complications of sleep apnea are predominantly mediated through nocturnal hypoxia, which has been associated with elevated nocturnal BP,20 left ventricular hypertrophy,21 and adverse cardiovascular outcomes in patients with ESRD.19,22 Although it is likely that sleep apnea may have a similar impact on clinical outcomes in patients with CKD, to our knowledge, this has not been studied to date. Furthermore, the potential interaction between nocturnal hypoxia and declining kidney function in patients with CKD is even more intriguing. Nocturnal hypoxia has been demonstrated to be independently associated with an increased risk for accelerated loss of kidney function.44 The chronic hypoxia hypothesis suggests that chronic ischemic damage in the tubulointerstitium of the kidney is the final common pathway for the development of ESRD.25,26 If such a process is already under way in patients with CKD, it is possible that ongoing nocturnal hypoxia will amplify the effect and accelerate the decline in kidney function. If so, identification and treatment of nocturnal hypoxia may provide a potential disease-modifying intervention that could delay or halt the progression of CKD to ESRD. Because a history of snoring and unrefreshing sleep were equally common among the three patient groups, objective cardiopulmonary evaluation may be required to identify these respiratory abnormalities.

The present study has a number of strengths. First, we recruited a relatively large sample from a renal population representative of the general CKD and ESRD populations. Second, we applied the same methodology to a broad spectrum of kidney disease, ranging from patients with eGFR ≥ 60 to ESRD. Third, we determined eGFR using the CKD-EPI equation, which is more reliable than what has been used in previous studies to estimate eGFR ≥ 60.

The study also has some limitations. First, the differences in neck size and prevalence of hypertension between the subjects who completed the study and those who withdrew raise the possibility of selection bias, which could result in an overestimation of the prevalence of sleep apnea. We tried to limit this by emphasizing that sleep-related symptoms were not required for recruitment and by using the same recruitment strategy and personnel for each group. Consequently, if such a selection bias did exist, we anticipate that it would have applied to all patients and that the difference in the prevalence of sleep apnea between groups would have been maintained. Further, as previously stated, the final study cohort was representative of the general CKD and ESRD populations. Second, we did not use a measurement of respiratory effort and, consequently, could only estimate the prevalence of central sleep apnea based on the morphology of the nasal pressure recording. Finally, we cannot comment on causality because of the cross-sectional nature of the study.

In conclusion, we have identified that patients with CKD are commonly exposed to nocturnal hypoxia related to both unrecognized sleep apnea and other factors. Nocturnal hypoxia has the potential to alter important clinical outcomes in this patient population, such as long-term cardiovascular risk and the rate of decline in kidney function. Further studies are required to determine whether treatment of sleep apnea and nocturnal hypoxia improves these clinical outcomes in patients with CKD.

Author contributions: Mr Nicholl and Dr Hanly had full access to all of the data in the study and take full responsibility for the integrity of the data and accuracy of the data analysis.

Mr Nicholl: contributed to the acquisition, analysis, and interpretation of the data and the drafting of the manuscript.

Dr Ahmed: contributed to the acquisition, analysis, and interpretation of the data and reviewed the manuscript for important intellectual content.

Dr Loewen: contributed to the conception and design of the study; acquisition, analysis, and interpretation of the data; and reviewed the manuscript for important intellectual content.

Dr Hemmelgarn: contributed to the acquisition, analysis, and interpretation of the data; statistical expertise; and reviewed the manuscript for important intellectual content.

Ms Sola: contributed to the acquisition, analysis, and interpretation of the data and final approval of the manuscript.

Mr Beecroft: contributed to the acquisition, analysis, and interpretation of the data and final approval of the manuscript.

Dr Turin: contributed statistical expertise and reviewed the manuscript for important intellectual content.

Dr Hanly: contributed to the conception and design of the study; acquisition, analysis, and interpretation of the data; drafting of the manuscript; and study supervision.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or in the preparation of the manuscript.

Other contributions: We thank the Southern Alberta Renal Program for patient recruitment, the Foothills Medical Centre Sleep Centre for sleep diagnostic testing, and Patty Nielsen for her clerical assistance.

CKD

chronic kidney disease

CKD-EPI

Chronic Kidney Disease Epidemiology Collaboration

CSR

Cheyne-Stokes respiration

eGFR

estimated glomerular filtration rate

ESRD

end-stage renal disease

OSA

obstructive sleep apnea

RDI

respiratory disturbance index

Sao2

arterial oxygen saturation

Hanly PJ, Pierratos A. Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis. N Engl J Med. 2001;3442:102-107. [CrossRef] [PubMed]
 
Kimmel PL, Miller G, Mendelson WB. Sleep apnea syndrome in chronic renal disease. Am J Med. 1989;863:308-314. [CrossRef] [PubMed]
 
Stepanski E, Faber M, Zorick F, Basner R, Roth T. Sleep disorders in patients on continuous ambulatory peritoneal dialysis. J Am Soc Nephrol. 1995;62:192-197. [PubMed]
 
Unruh ML, Sanders MH, Redline S, et al. Sleep apnea in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the Sleep Heart Health Study. J Am Soc Nephrol. 2006;1712:3503-3509. [CrossRef] [PubMed]
 
Wadhwa NK, Mendelson WB. A comparison of sleep-disordered respiration in ESRD patients receiving hemodialysis and peritoneal dialysis. Adv Perit Dial. 1992;8:195-198. [PubMed]
 
Wadhwa NK, Seliger M, Greenberg HE, Bergofsky E, Mendelson WB. Sleep related respiratory disorders in end-stage renal disease patients on peritoneal dialysis. Perit Dial Int. 1992;121:51-56. [PubMed]
 
Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;32817:1230-1235. [CrossRef] [PubMed]
 
Canales MT, Lui LY, Taylor BC, et al; Osteoporotic Fractures in Men (MrOS) Study Group Osteoporotic Fractures in Men (MrOS) Study Group Renal function and sleep-disordered breathing in older men. Nephrol Dial Transplant. 2008;2312:3908-3914. [CrossRef] [PubMed]
 
Roumelioti ME, Buysse DJ, Sanders MH, Strollo P, Newman AB, Unruh ML. Sleep-disordered breathing and excessive daytime sleepiness in chronic kidney disease and hemodialysis. Clin J Am Soc Nephrol. 2011;65:986-994. [CrossRef] [PubMed]
 
Markou N, Kanakaki M, Myrianthefs P, et al. Sleep-disordered breathing in nondialyzed patients with chronic renal failure. Lung. 2006;1841:43-49. [CrossRef] [PubMed]
 
Sakaguchi Y, Shoji T, Kawabata H, et al. High prevalence of obstructive sleep apnea and its association with renal function among nondialysis chronic kidney disease patients in Japan: a cross-sectional study. Clin J Am Soc Nephrol. 2011;65:995-1000. [CrossRef] [PubMed]
 
Sim JJ, Rasgon SA, Kujubu DA, et al. Sleep apnea in early and advanced chronic kidney disease: Kaiser Permanente Southern California cohort. Chest. 2009;1353:710-716. [CrossRef] [PubMed]
 
Heslegrave R, Thornley K, Ouwendyk M, et al. Impact of nocturnal hemodialysis on sleep and daytime cognitive functioning in patients with chronic renal failure [abstract]. Sleep. 1998;21:51
 
Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;34219:1378-1384. [CrossRef] [PubMed]
 
Larkin EK, Rosen CL, Kirchner HL, et al. Variation of C-reactive protein levels in adolescents: association with sleep-disordered breathing and sleep duration. Circulation. 2005;11115:1978-1984. [CrossRef] [PubMed]
 
Bloembergen WE, Port FK, Mauger EA, Wolfe RA. A comparison of cause of death between patients treated with hemodialysis and peritoneal dialysis. J Am Soc Nephrol. 1995;62:184-191. [PubMed]
 
Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;3659464:1046-1053. [PubMed]
 
Redline S, Yenokyan G, Gottlieb DJ, et al. Obstructive sleep apnea-hypopnea and incident stroke: the Sleep Heart Health study. Am J Respir Crit Care Med. 2010;1822:269-277. [CrossRef] [PubMed]
 
Zoccali C, Mallamaci F, Tripepi G. Traditional and emerging cardiovascular risk factors in end-stage renal disease. Kidney Int Suppl. 2003;85:S105-S110
 
Zoccali C, Benedetto FA, Tripepi G, et al. Nocturnal hypoxemia, night-day arterial pressure changes and left ventricular geometry in dialysis patients. Kidney Int. 1998;534:1078-1084. [CrossRef] [PubMed]
 
Zoccali C, Benedetto FA, Mallamaci F, et al. Left ventricular hypertrophy and nocturnal hypoxemia in hemodialysis patients. J Hypertens. 2001;192:287-293. [CrossRef] [PubMed]
 
Zoccali C, Mallamaci F, Tripepi G. Nocturnal hypoxemia predicts incident cardiovascular complications in dialysis patients. J Am Soc Nephrol. 2002;133:729-733. [CrossRef] [PubMed]
 
Zoccali C, Mallamaci F, Tripepi G. Sleep apnea in renal patients. J Am Soc Nephrol. 2001;1212:2854-2859. [PubMed]
 
Fletcher EC. Obstructive sleep apnea and the kidney. J Am Soc Nephrol. 1993;45:1111-1121. [PubMed]
 
Fine LG, Orphanides C, Norman JT. Progressive renal disease: the chronic hypoxia hypothesis. Kidney Int Suppl. 1998;65:S74-S78. [PubMed]
 
Fine LG, Norman JT. Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics. Kidney Int. 2008;747:867-872. [CrossRef] [PubMed]
 
Levey AS, Coresh J, Balk E, et al; National Kidney Foundation National Kidney Foundation National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;1392:137-147. [PubMed]
 
Levey AS, Stevens LA, Schmid CH, et al; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;1509:604-612. [PubMed]
 
Issa FG, Morrison D, Hadjuk E, Iyer A, Feroah T, Remmers JE. Digital monitoring of sleep-disordered breathing using snoring sound and arterial oxygen saturation. Am Rev Respir Dis. 1993;1484 pt 1:1023-1029. [CrossRef] [PubMed]
 
Vázquez JC, Tsai WH, Flemons WW, et al. Automated analysis of digital oximetry in the diagnosis of obstructive sleep apnoea. Thorax. 2000;554:302-307. [CrossRef] [PubMed]
 
Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999;225:667-689. [PubMed]
 
Epstein LJ, Kristo D, Strollo PJ Jr, et al; Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009;53:263-276. [PubMed]
 
Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000;28314:1829-1836. [CrossRef] [PubMed]
 
Oğretmenoğlu O, Süslü AE, Yücel OT, Onerci TM, Sahin A. Body fat composition: a predictive factor for obstructive sleep apnea. Laryngoscope. 2005;1158:1493-1498. [CrossRef] [PubMed]
 
Adeseun GA, Rosas SE. The impact of obstructive sleep apnea on chronic kidney disease. Curr Hypertens Rep. 2010;125:378-383. [CrossRef] [PubMed]
 
Stevens LA, Schmid CH, Greene T, et al. Comparative performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study equations for estimating GFR levels above 60 mL/min/1.73 m2Am J Kidney Dis. 2010;563:486-495. [CrossRef] [PubMed]
 
Hemmelgarn BR, Manns BJ, Quan H, Ghali WA. Adapting the Charlson Comorbidity Index for use in patients with ESRD. Am J Kidney Dis. 2003;421:125-132. [CrossRef] [PubMed]
 
Lash JP, Go AS, Appel LJ, et al; Chronic Renal Insufficiency Cohort (CRIC) Study Group Chronic Renal Insufficiency Cohort (CRIC) Study Group Chronic Renal Insufficiency Cohort (CRIC) Study: baseline characteristics and associations with kidney function. Clin J Am Soc Nephrol. 2009;48:1302-1311. [CrossRef] [PubMed]
 
Tang SC, Lam B, Lai AS, et al. Improvement in sleep apnea during nocturnal peritoneal dialysis is associated with reduced airway congestion and better uremic clearance. Clin J Am Soc Nephrol. 2009;42:410-418. [CrossRef] [PubMed]
 
Beecroft J, Duffin J, Pierratos A, Chan CT, McFarlane P, Hanly PJ. Enhanced chemo-responsiveness in patients with sleep apnoea and end-stage renal disease. Eur Respir J. 2006;281:151-158. [CrossRef] [PubMed]
 
Beecroft JM, Duffin J, Pierratos A, Chan CT, McFarlane P, Hanly PJ. Decreased chemosensitivity and improvement of sleep apnea by nocturnal hemodialysis. Sleep Med. 2009;101:47-54. [CrossRef] [PubMed]
 
Beecroft JM, Hoffstein V, Pierratos A, Chan CT, McFarlane PA, Hanly PJ. Pharyngeal narrowing in end-stage renal disease: implications for obstructive sleep apnoea. Eur Respir J. 2007;305:965-971. [CrossRef] [PubMed]
 
Beecroft JM, Hoffstein V, Pierratos A, Chan CT, McFarlane P, Hanly PJ. Nocturnal haemodialysis increases pharyngeal size in patients with sleep apnoea and end-stage renal disease. Nephrol Dial Transplant. 2008;232:673-679. [CrossRef] [PubMed]
 
Ahmed SB, Ronksley PE, Hemmelgarn BR, et al. Nocturnal hypoxia and loss of kidney function. PLoS ONE. 2011;64:e19029. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Nocturnal cardiopulmonary recording demonstrating Cheyne-Stokes respiration and obstructive sleep apnea. Each example is 10 min. HR = heart rate; NP = nasal pressure; SaO2 = arterial oxygen saturation.Grahic Jump Location
Figure Jump LinkFigure 2. Patient recruitment. PSG = polysomnography; RSR = Remmers Sleep Recorder.Grahic Jump Location
Figure Jump LinkFigure 3. Prevalence of sleep apnea in all patients. CKD = chronic kidney disease; CSR = Cheyne-Stokes respiration; eGFR ≥ 60 = estimated glomerular filtration rate ≥ 60 mL/min/1.73 m2; ESRD = end-stage renal disease; OSA = obstructive sleep apnea; RDI = respiratory disturbance index.Grahic Jump Location
Figure Jump LinkFigure 4. Prevalence of nocturnal hypoxia in all patients. See Figure 1 and 3 legends for expansion of abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Clinical Profile of Patients Who Completed the Study Compared With Patients Who Withdrew From the Study

Data are presented as mean ± SD or No. (%), unless otherwise indicated. CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease.

Table Graphic Jump Location
Table 2 —Clinical Profile of All Patients Who Completed the Study

Data are presented as mean ± SD, No. (%), or median (range), unless otherwise indicated. See Table 1 legend for expansion of abbreviations.

a 

CKD (eGFR < 60 mL/min/1.73 m).

b 

ESRD (on hemodialysis).

Table Graphic Jump Location
Table 3 —Prevalence of Sleep Apnea and Nocturnal Hypoxia in All Patients

Data are presented as median (range) or No.(%), unless otherwise indicated. RDI = respiratory disturbance index; Sao2 = arterial oxygen saturation; TTPO = total time oximeter probe was on the patient. See Table 1 legend for expansion of other abbreviations.

a 

CKD (eGFR < 60 mL/min/1.73 m).

b 

ESRD (on hemodialysis).

Table Graphic Jump Location
Table 4 —Univariate and Multivariate Analyses for Sleep Apnea and Nocturnal Hypoxia

See Table 1 and 3 legends for expansion of abbreviations.

a 

Sleep apnea RDI ≥ 15.

b 

Nocturnal hypoxia Sao2 < 90% for ≥ 12% of monitoring time.

References

Hanly PJ, Pierratos A. Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis. N Engl J Med. 2001;3442:102-107. [CrossRef] [PubMed]
 
Kimmel PL, Miller G, Mendelson WB. Sleep apnea syndrome in chronic renal disease. Am J Med. 1989;863:308-314. [CrossRef] [PubMed]
 
Stepanski E, Faber M, Zorick F, Basner R, Roth T. Sleep disorders in patients on continuous ambulatory peritoneal dialysis. J Am Soc Nephrol. 1995;62:192-197. [PubMed]
 
Unruh ML, Sanders MH, Redline S, et al. Sleep apnea in patients on conventional thrice-weekly hemodialysis: comparison with matched controls from the Sleep Heart Health Study. J Am Soc Nephrol. 2006;1712:3503-3509. [CrossRef] [PubMed]
 
Wadhwa NK, Mendelson WB. A comparison of sleep-disordered respiration in ESRD patients receiving hemodialysis and peritoneal dialysis. Adv Perit Dial. 1992;8:195-198. [PubMed]
 
Wadhwa NK, Seliger M, Greenberg HE, Bergofsky E, Mendelson WB. Sleep related respiratory disorders in end-stage renal disease patients on peritoneal dialysis. Perit Dial Int. 1992;121:51-56. [PubMed]
 
Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;32817:1230-1235. [CrossRef] [PubMed]
 
Canales MT, Lui LY, Taylor BC, et al; Osteoporotic Fractures in Men (MrOS) Study Group Osteoporotic Fractures in Men (MrOS) Study Group Renal function and sleep-disordered breathing in older men. Nephrol Dial Transplant. 2008;2312:3908-3914. [CrossRef] [PubMed]
 
Roumelioti ME, Buysse DJ, Sanders MH, Strollo P, Newman AB, Unruh ML. Sleep-disordered breathing and excessive daytime sleepiness in chronic kidney disease and hemodialysis. Clin J Am Soc Nephrol. 2011;65:986-994. [CrossRef] [PubMed]
 
Markou N, Kanakaki M, Myrianthefs P, et al. Sleep-disordered breathing in nondialyzed patients with chronic renal failure. Lung. 2006;1841:43-49. [CrossRef] [PubMed]
 
Sakaguchi Y, Shoji T, Kawabata H, et al. High prevalence of obstructive sleep apnea and its association with renal function among nondialysis chronic kidney disease patients in Japan: a cross-sectional study. Clin J Am Soc Nephrol. 2011;65:995-1000. [CrossRef] [PubMed]
 
Sim JJ, Rasgon SA, Kujubu DA, et al. Sleep apnea in early and advanced chronic kidney disease: Kaiser Permanente Southern California cohort. Chest. 2009;1353:710-716. [CrossRef] [PubMed]
 
Heslegrave R, Thornley K, Ouwendyk M, et al. Impact of nocturnal hemodialysis on sleep and daytime cognitive functioning in patients with chronic renal failure [abstract]. Sleep. 1998;21:51
 
Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med. 2000;34219:1378-1384. [CrossRef] [PubMed]
 
Larkin EK, Rosen CL, Kirchner HL, et al. Variation of C-reactive protein levels in adolescents: association with sleep-disordered breathing and sleep duration. Circulation. 2005;11115:1978-1984. [CrossRef] [PubMed]
 
Bloembergen WE, Port FK, Mauger EA, Wolfe RA. A comparison of cause of death between patients treated with hemodialysis and peritoneal dialysis. J Am Soc Nephrol. 1995;62:184-191. [PubMed]
 
Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;3659464:1046-1053. [PubMed]
 
Redline S, Yenokyan G, Gottlieb DJ, et al. Obstructive sleep apnea-hypopnea and incident stroke: the Sleep Heart Health study. Am J Respir Crit Care Med. 2010;1822:269-277. [CrossRef] [PubMed]
 
Zoccali C, Mallamaci F, Tripepi G. Traditional and emerging cardiovascular risk factors in end-stage renal disease. Kidney Int Suppl. 2003;85:S105-S110
 
Zoccali C, Benedetto FA, Tripepi G, et al. Nocturnal hypoxemia, night-day arterial pressure changes and left ventricular geometry in dialysis patients. Kidney Int. 1998;534:1078-1084. [CrossRef] [PubMed]
 
Zoccali C, Benedetto FA, Mallamaci F, et al. Left ventricular hypertrophy and nocturnal hypoxemia in hemodialysis patients. J Hypertens. 2001;192:287-293. [CrossRef] [PubMed]
 
Zoccali C, Mallamaci F, Tripepi G. Nocturnal hypoxemia predicts incident cardiovascular complications in dialysis patients. J Am Soc Nephrol. 2002;133:729-733. [CrossRef] [PubMed]
 
Zoccali C, Mallamaci F, Tripepi G. Sleep apnea in renal patients. J Am Soc Nephrol. 2001;1212:2854-2859. [PubMed]
 
Fletcher EC. Obstructive sleep apnea and the kidney. J Am Soc Nephrol. 1993;45:1111-1121. [PubMed]
 
Fine LG, Orphanides C, Norman JT. Progressive renal disease: the chronic hypoxia hypothesis. Kidney Int Suppl. 1998;65:S74-S78. [PubMed]
 
Fine LG, Norman JT. Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics. Kidney Int. 2008;747:867-872. [CrossRef] [PubMed]
 
Levey AS, Coresh J, Balk E, et al; National Kidney Foundation National Kidney Foundation National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;1392:137-147. [PubMed]
 
Levey AS, Stevens LA, Schmid CH, et al; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;1509:604-612. [PubMed]
 
Issa FG, Morrison D, Hadjuk E, Iyer A, Feroah T, Remmers JE. Digital monitoring of sleep-disordered breathing using snoring sound and arterial oxygen saturation. Am Rev Respir Dis. 1993;1484 pt 1:1023-1029. [CrossRef] [PubMed]
 
Vázquez JC, Tsai WH, Flemons WW, et al. Automated analysis of digital oximetry in the diagnosis of obstructive sleep apnoea. Thorax. 2000;554:302-307. [CrossRef] [PubMed]
 
Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep. 1999;225:667-689. [PubMed]
 
Epstein LJ, Kristo D, Strollo PJ Jr, et al; Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine Adult Obstructive Sleep Apnea Task Force of the American Academy of Sleep Medicine Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009;53:263-276. [PubMed]
 
Nieto FJ, Young TB, Lind BK, et al. Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study. JAMA. 2000;28314:1829-1836. [CrossRef] [PubMed]
 
Oğretmenoğlu O, Süslü AE, Yücel OT, Onerci TM, Sahin A. Body fat composition: a predictive factor for obstructive sleep apnea. Laryngoscope. 2005;1158:1493-1498. [CrossRef] [PubMed]
 
Adeseun GA, Rosas SE. The impact of obstructive sleep apnea on chronic kidney disease. Curr Hypertens Rep. 2010;125:378-383. [CrossRef] [PubMed]
 
Stevens LA, Schmid CH, Greene T, et al. Comparative performance of the CKD Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) Study equations for estimating GFR levels above 60 mL/min/1.73 m2Am J Kidney Dis. 2010;563:486-495. [CrossRef] [PubMed]
 
Hemmelgarn BR, Manns BJ, Quan H, Ghali WA. Adapting the Charlson Comorbidity Index for use in patients with ESRD. Am J Kidney Dis. 2003;421:125-132. [CrossRef] [PubMed]
 
Lash JP, Go AS, Appel LJ, et al; Chronic Renal Insufficiency Cohort (CRIC) Study Group Chronic Renal Insufficiency Cohort (CRIC) Study Group Chronic Renal Insufficiency Cohort (CRIC) Study: baseline characteristics and associations with kidney function. Clin J Am Soc Nephrol. 2009;48:1302-1311. [CrossRef] [PubMed]
 
Tang SC, Lam B, Lai AS, et al. Improvement in sleep apnea during nocturnal peritoneal dialysis is associated with reduced airway congestion and better uremic clearance. Clin J Am Soc Nephrol. 2009;42:410-418. [CrossRef] [PubMed]
 
Beecroft J, Duffin J, Pierratos A, Chan CT, McFarlane P, Hanly PJ. Enhanced chemo-responsiveness in patients with sleep apnoea and end-stage renal disease. Eur Respir J. 2006;281:151-158. [CrossRef] [PubMed]
 
Beecroft JM, Duffin J, Pierratos A, Chan CT, McFarlane P, Hanly PJ. Decreased chemosensitivity and improvement of sleep apnea by nocturnal hemodialysis. Sleep Med. 2009;101:47-54. [CrossRef] [PubMed]
 
Beecroft JM, Hoffstein V, Pierratos A, Chan CT, McFarlane PA, Hanly PJ. Pharyngeal narrowing in end-stage renal disease: implications for obstructive sleep apnoea. Eur Respir J. 2007;305:965-971. [CrossRef] [PubMed]
 
Beecroft JM, Hoffstein V, Pierratos A, Chan CT, McFarlane P, Hanly PJ. Nocturnal haemodialysis increases pharyngeal size in patients with sleep apnoea and end-stage renal disease. Nephrol Dial Transplant. 2008;232:673-679. [CrossRef] [PubMed]
 
Ahmed SB, Ronksley PE, Hemmelgarn BR, et al. Nocturnal hypoxia and loss of kidney function. PLoS ONE. 2011;64:e19029. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543