| | Decreased chemosensitivity and improvement of sleep apnea by nocturnal hemodialysisReceived 22 August 2007; received in revised form 15 November 2007; accepted 16 November 2007. Abstract Background:Sleep apnea occurs in up to 50% of patients with end-stage renal disease and is improved by nocturnal hemodialysis. We hypothesized that its pathogenesis is related to changes in chemoreflex responsiveness. Methods:Twenty-four patients receiving conventional hemodialysis (4 h/day, 3 times/week) had overnight polysomnography and measurement of the ventilatory response to carbon dioxide during isoxic hypoxia and hyperoxia using a modified rebreathing technique. Measurements were repeated following conversion from conventional to nocturnal hemodialysis (8h/night, 3–6 nights/week). Patients were divided into apneic and non-apneic groups based on apnea–hypopnea index ⩾15/h at baseline (17 apneics and 7 non-apneics), and the apneic group was further divided into “responders” and “non-responders” based on a significant reduction in AHI at follow-up. Conclusions:Improvement of sleep apnea following conversion from conventional to nocturnal hemodialysis is associated with a decrease in chemoreflex responsiveness. This finding suggests that increased chemoreflex responsiveness contributes to the pathogenesis of sleep apnea in some patients with end-stage renal disease. 1. Introduction  Sleep apnea has been reported in 50% or more of patients with end-stage renal disease (ESRD) [1], which is at least ten times higher than the prevalence reported in the general population [2]. The pathogenesis of sleep apnea in patients with ESRD remains unclear. Previous investigators have observed features of both central and obstructive sleep apnea (OSA) in patients with ESRD [3], [4], [5], [6], [7], [8], [9], which suggests that its pathogenesis is related both to destabilization of central respiratory control and upper airway occlusion. We have recently reported an increased ventilatory sensitivity to hypercapnia in ESRD patients with OSA [10]. This increased sensitivity can destabilize the chemoreflex control of respiration during sleep and may play a role in the pathogenesis of both obstructive [11] and central sleep apnea [12], [13], [14]. Although sleep apnea is not corrected by conventional hemodialysis (CHD) [4], [7], it is improved by nocturnal hemodialysis (NHD) [4], which may alter respiratory control in several ways. Firstly, improved clearance of uremic toxins and slower, more frequent hemodialysis [15] may reverse chemoreceptor activation caused by uremia or dialysis itself [16]. Secondly, improved ultrafiltration and/or improved ventricular function associated with NHD [17] may provide more effective clearance of extracellular fluid and thereby reduce the mechanoreceptor stimulation of respiration caused by interstitial pulmonary edema [18]. Thirdly, conversion from CHD to NHD results in the normalization of elevated sympathetic nervous system activation associated with ESRD [19]. Sympathetic activation is associated with potentiation of the chemoreflex response in healthy subjects [20]. We hypothesized that conversion from CHD to NHD decreases chemoreflex responsiveness and that this change is associated with an improvement in the severity of sleep apnea. The specific objectives of this study were to assess whether the ventilatory response to hypercapnia is reduced in patients with ESRD following conversion from CHD to NHD and to determine whether such changes are associated with a reduction in the apnea–hypopnea index (AHI). 2. Methods 2.1. Patient recruitment and study protocol Patients enrolled in the home NHD program at Humber River Regional Hospital, St. Michael’s Hospital and the Toronto General Hospital were invited to participate in the study. All patients who entered the study were receiving treatment with CHD for four hours, on three days per week and were considered candidates for home hemodialysis training. Baseline studies were performed during treatment with CHD and consisted of overnight polysomnography, (performed and scored by registered polysomnographic technologists according to published criteria) [21] as previously described [4] and measurements of chemoreflex responsiveness. Patients then underwent five to six weeks of home hemodialysis training and were restudied once they were using NHD at home without difficulty, which was usually three to six months later. NHD was performed during sleep for six to ten hours per night, on three to six nights per week using high flux polysulfone dialyzers (Fresenius Medical Care, Lexington, MA). A venous blood sample was drawn to determine blood urea nitrogen (BUN) and serum creatinine. Effectiveness of hemodialysis was determined by estimating the percent reduction in urea per dialysis session (PRU) [22], which was obtained from the dialysis clinics at baseline and follow-up. Baseline measurements were performed within 24h of the most recent dialysis session and follow-up measurements were performed on a night when the patient was not undergoing NHD. The study protocol was reviewed and approved by the research ethics board at St. Michael’s Hospital, and all patients gave written informed consent to participate in the study. 2.2. Chemoreflex responsiveness Chemoreflex responsiveness was measured using a modified [23], [24], [25] Read [26] rebreathing technique. The modifications were as follows: (1) five minutes of prior hyperventilation to facilitate sub- and supra-threshold measures of ventilation, enabling the ventilatory recruitment threshold to carbon dioxide to be measured directly rather than by extrapolation; (2) maintenance of isoxia throughout the test, enabling the contribution of the peripheral chemoreflex to be varied. Measurements were obtained during isoxic hypoxia ( =50 mmHg) and isoxic hyperoxia ( =150 mmHg) and changes in ventilation were measured as the level of  rose. The main test parameters obtained were: sub-threshold or basal ventilation (VEb), ventilatory threshold for carbon dioxide (T), and supra-threshold slope termed ventilatory sensitivity (S) (Fig. 1). When the test is performed during hypoxia, the ventilatory response reflects the activity of the central and peripheral chemoreflexes, but when it is done during hyperoxia, the ventilatory response reflects the activity of the central chemorereflex alone as hyperoxia markedly attenuates the activity of the peripheral chemoreceptors. All measures of chemoreflex responsiveness were performed during wakefulness at the time of polysomnography, before and after conversion from CHD to NHD. In addition, blood was drawn from the radial artery to determine arterial blood gases. A complete description of the rebreathing equipment and collection and analysis protocols has been published previously [27]. 2.3. Analysis Mean data were analyzed using a one-way analysis of variance with Tukey post hoc analysis at baseline, repeated measures analysis of variance at follow-up and one-way analysis of the change within each group with Tukey post hoc analysis. Sub-group analysis was performed using a repeated measures analysis of variance. Relationships between variables were analyzed using Pearson correlation. Nominal data were analyzed using chi-square analysis. All statistical analysis was performed using computer software (SPSS 14.0, SPSS Inc., Chicago, IL). All p values <0.05 were considered statistically significant. 3. Results 3.1. Patient demographics Twenty-four patients (15 male, 9 female), aged 31–68 years, were studied. Patients were divided into apneic and non-apneic groups based on an apnea–hypopnea index (AHI) of 15 or more events/h during baseline polysomnography. Sleep apnea was present in 17 patients (71%). Following conversion from CHD to NHD, apneic patients were classified as “responders” if AHI fell >50% and/or was reduced to <15 events/h. Four out of 17 apneic patients (24%) met these criteria. Patient demographic data are shown in Table 1. There were no significant inter-group differences in age, gender or body mass index (BMI), although non-responders tended to be older and predominantly male. Chronic glomerulonephritis was the most common cause of ESRD, followed by diabetes mellitus, hypertension and polycystic kidney disease. In two patients, the cause of ESRD was unclear. No patients suffered from chronic heart failure. One patient had a history of mild asthma, which was well controlled at the time of the study. | | |  | | Apneic | Non-apneic | |
|---|
| | Responder | Non-responder | | |
|---|
| Patients (n) | 4 | 13 | 7 | | | Male/female | 1/3 | 9/4 | 5/2 | | | Age (years) | 39.5±6.1 | 52.2±10.9 | 43.3±9.1 | | | BMI (kg/m2) | 30.8±11.1 | 29.4±5.5 | 23.4±4.0 | | | | | | | | | Cause of ESRD | | | Diabetes | 1 | 3 | 0 | | | Hypertension | 1 | 3 | 0 | | | Glomerulonephritis | 1 | 7 | 3 | | | PCKD | 1 | 0 | 2 | | | Cryptogenic | 0 | 0 | 2 | | | Months on dialysis | 15±16 | 18±16 | 42±77 | | | | |
During treatment with CHD, there were no inter-group differences in PRU, BUN or serum creatinine (Table 2). Conversion from CHD to NHD was associated with a significant increase in PRU and a reduction in serum creatinine, and the extent of these changes were similar between groups. There were no significant changes in BMI following conversion from CHD to NHD. | | | | | Apneic | Non-apneic | |
|---|
| | Responder | Non-responder | |
|---|
| | CHD | NHD | CHD | NHD | CHD | NHD | |
|---|
| PRU (%)a | 78.8±7.4 | 82.1±11.2 | 72.9±11.8 | 82.8±13.2 | 69.3±14.9 | 84.7±6.3 | | | BUN (mmol/L) | 9.0±1.9 | 9.8±1.1 | 15.8±5.0 | 13.5±6.1 | 13.3±4.7 | 11.5±5.8 | | | Creatinine (μmol/L)b | 549±111 | 468±56 | 716±247 | 604±323 | 659±162 | 534±166 | | | | |
3.3. Chemoreflex responsiveness The results of the rebreathing tests are shown in Table 5. On CHD, there were no significant inter-group differences in basal ventilation, ventilatory recruitment threshold or the rate of rise of carbon dioxide during rebreathing tests. Ventilatory sensitivity tended to be higher in apneic than non-apneic patients (hypoxia: 7.0±4.1 vs. 3.1±1.5, p=0.174; hyperoxia: 2.9±1.2 vs. 1.9±1.1, p=0.081). Furthermore, there was a significant positive correlation between AHI and ventilatory sensitivity during both hypoxia and hyperoxia in apneic patients (hypoxia: r=.475, p=0.034; hyperoxia: r=.668, p<0.001). Following conversion from CHD to NHD, there were no changes in basal ventilation, ventilatory recruitment threshold or the rate of the rise of carbon dioxide during hypoxic and hyperoxic rebreathing tests. Ventilatory sensitivity was not different between CHD and NHD when all patients were analyzed (hypoxia: 5.6±3.9L/min/mmHg vs. 4.9±1.7L/min/mmHg; hyperoxia: 2.6±1.3L/min/mmHg vs. 2.5±1.4L/min/mmHg). However, ventilatory sensitivity tended to fall in apneics (hypoxia: 7.0±4.1L/min/mmHg vs. 5.7±3.2L/min/mmHg; hyperoxia: 2.9±1.2L/min/mmHg vs. 2.8±1.5L/min/mmHg) and to increase in non-apneics (hypoxia: 3.1±1.5L/min/mmHg vs. 4.4±2.8L/min/mmHg; hyeroxia: 1.9±1.1L/min/mmHg vs. 2.0±1.1L/min/mmHg). Furthermore, the reduction in ventilatory sensitivity among apneic patients was seen almost exclusively in responders and reached statistical significance during hyperoxia but not during hypoxia (Table 5, Fig. 2). Statistical power for comparison of the change in ventilatory sensitivity during hyperoxia in apneic responders vs. non-responders was 86.7%. In addition, there was a positive correlation between the change in ventilatory sensitivity and the change in AHI associated with conversion to NHD (Fig. 3), which reached significance during hyperoxia (r=.528, p=0.029) but not during hypoxia (r=.525, p=0.065). 4. Discussion Sleep apnea is common in patients with ESRD [4], [5], [7], [8], [9], although its pathogenesis remains unclear. We have previously reported increased ventilatory sensitivity to hypercapnia in ESRD patients with OSA [10], which may indicate that chemoreflex responsiveness plays an important pathophysiologic role in the development of OSA in this patient population. In the present study, we found that in patients whose sleep apnea improved following conversion from CHD to NHD, the ventilatory sensitivity to hypercapnia during isoxic hyperoxia decreased, indicating a decrease in the sensitivity of the central chemoreceptors. Although these findings are based on a small number of responders, we also noted that the change in ventilatory sensitivity correlated with the change in AHI in all apneic patients. These data suggest that NHD may improve sleep apnea in ESRD patients by decreasing ventilatory sensitivity and thereby stabilizing the chemical control of breathing. Increased dependence on chemical control of respiration during non-rapid eye movement sleep [28] makes the system more vulnerable to changes in the level of arterial  . Hypoxia and hypercapnia that develop during apnea stimulate the respiratory chemoreflexes, which increases ventilation. If the ventilatory response is excessive, hypocapnia results, which reduces central motor respiratory output, thereby continuing the cycle of alternating apnea and hyperpnea [29]. Increased chemoreflex sensitivity promotes and perpetuates this unstable breathing pattern. Furthermore, central respiratory instability can be accompanied by obstructive apnea if the upper airway is predisposed to occlusion, for example, by pharyngeal narrowing or increased compliance [30], or if there is a disproportionately greater drive to the inspiratory pump muscles than the upper airway dilators during resumption of breathing [31], [32]. Consequently, decreased chemoreflex sensitivity, following conversion from CHD to NHD, may correct sleep apnea by decreasing respiratory control system loop gain, which stabilizes the control of ventilation [29]. The mechanism(s) responsible for the chemoreflex changes we observed remain unclear. Obesity is associated with potentiation of central chemoreflex sensitivity [33], which may reverse following weight loss. However, weight loss does not explain our findings since BMI was not significantly different between CHD and NHD. Decreased ventilatory sensitivity does not appear to be related to differences in the effectiveness of dialysis since changes in serum creatinine and PRU associated with conversion from CHD to NHD, were similar between groups. Decreased ventilatory sensitivity is not due to changes in blood gas tensions since the conversion from CHD to NHD did not alter arterial or transcutaneous  . In addition, acid–base disturbances have little or no effect on the sensitivity of the central chemoreflex response [34], [35]. Antihypertensive medication and erythropoetin requirements generally decrease following conversion from CHD to NHD and in some cases these medications may be discontinued altogether [36]. These changes do not explain our findings however, since medication changes were similar between groups. Finally, respiratory chemoreflex responsiveness has been shown to vary with the phase of the menstrual cycle [37]. Although we did not standardize the timing of our measurements with respect to the menstrual cycle, the majority of women in our study were of postmenopausal age (>55 years), and most premenopausal women receiving hemodialysis are amenorrheic [38]. Consequently, it is unlikely that differences in the time of the menstrual phase are responsible for the changes we observed. We are left to speculate on other potential reasons for decreased ventilatory sensitivity that were not measured in this study. In patients with congestive heart failure, increased pulmonary mechanoreceptor stimulation associated with interstitial pulmonary edema is thought to increase mechanoreceptor stimulation sensitivity, thereby destabilizing the control of breathing and contributing to the pathogenesis of sleep apnea [12], [18]. Patients with ESRD are predisposed to develop interstitial pulmonary edema due to fluid overload and co-existing impairment of cardiac function [39], [40]. Nocturnal hemodialysis is associated with improved blood pressure control, greater hemodynamic stability and reduction of extracellular fluid volume [17], all of which may correct pulmonary edema more effectively than CHD and thereby improve sleep apnea. However, our data do not support this mechanism since arterial  and transcutaneous  recorded during sleep were similar between patients with and without sleep apnea and did not change following conversion from CHD to NHD. More thorough investigation of fluid status and cardiovascular function, including markers such as brain natriuretic peptide, may provide valuable insight into whether these mechanisms are involved. End-stage renal disease is characterized by the accumulation of middle-molecules and other substances which are normally cleared by healthy kidneys but not by CHD [41]. The effect of such changes on respiratory chemoreflex control has not been investigated. Nocturnal hemodialysis has been shown to partially reverse the accumulation of middle-molecules [41], which may explain the changes in ventilatory sensitivity we observed.An alternative explanation involves the effect of the sympathetic nervous system on chemoreflex responsiveness. End-stage renal disease is associated with sympathetic nervous system activation [42], which is corrected by conversion from CHD to NHD [19]. Sympathetic activation and chemoreflex sensitivity are co-related in healthy subjects [20] and changes in ventilatory sensitivity and subsequent correction of sleep apnea in patients receiving NHD may therefore be related to normalization of sympathetic nervous system activity. In contrast to previous work [4], conversion from CHD to NHD did not correct sleep apnea in the majority of our patients. This discrepancy may be related to a number of factors, including the scheduling and timing of dialysis. Dialysis schedules for patients in this study varied from alternate nights (i.e., three to four nights/week) to five or six nights/week, in contrast to six nights/week that was used previously [4]. In addition, our patients were studied on a night while they were not undergoing NHD, a period during which sleep apnea may partially return [4]. Further investigation is necessary to determine the optimal amount of NHD that is required to correct sleep apnea. Alternatively, some of our non-responders may have developed sleep apnea independently of renal failure and consequently would not be expected to benefit from a change in the mode of dialysis and associated change in chemoreflex sensitivity. This possibility is supported by the tendency for non-responders to be older than responders and predominantly male, both of which are risk factors for the development of OSA in the general population [43]. In addition, we have previously shown that conversion from CHD to NHD is associated with an increase in pharyngeal cross-sectional area, which tended to be greatest among apneic responders [44]. These findings may indicate non-responders have some upper airway abnormality that developed independently of renal failure. Selection of patients whose sleep apnea developed in association with ESRD may have yielded a higher proportion of “responders”. In summary, correction of sleep apnea by NHD is associated with a decrease in respiratory chemoreflex sensitivity to hypercapnia during isoxic hyperoxia. These data indicate a decrease in the sensitivity of the central chemoreflex response. Since a decrease in chemoreflex sensitivity stabilizes the respiratory control system, we suggest these changes contribute to the correction of sleep apnea following conversion from CHD to NHD. Further studies are required to determine why chemoreflex sensitivity is increased in ESRD and how this is reduced by NHD. References [1]. [1]Kraus MA, Hamburger RJ. Sleep apnea in renal failure. Adv Perit Dial. 1997;13:88–92. MEDLINE [2]. [2]Young T, Palta M, Dempsey J, et al. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med. 1993;328:1230–1235. MEDLINE |
CrossRef
[3]. [3]Auckley DH, Schmidt-Nowara W, Brown LK. Reversal of sleep apnea hypopnea syndrome in end-stage renal disease after kidney transplantation. Am J Kidney Dis. 1999;34:739–744. Abstract | Full Text |
Full-Text PDF (40 KB)
|
CrossRef
[4]. [4]Hanly PJ, Pierratos A. Improvement of sleep apnea in patients with chronic renal failure who undergo nocturnal hemodialysis. N Engl J Med. 2001;344:102–107. MEDLINE |
CrossRef
[5]. [5]Kimmel PL, Miller G, Mendelson WB. Sleep apnea syndrome in chronic renal disease. Am J Med. 1989;86:308–314. Abstract |
Full-Text PDF (957 KB)
|
CrossRef
[6]. [6]Langevin B, Fouque D, Leger P, et al. Sleep apnea syndrome and end-stage renal disease. Cure after renal transplantation. Chest. 1993;103:1330–1335. MEDLINE |
CrossRef
[7]. [7]Mendelson WB, Wadhwa NK, Greenberg HE, et al. Effects of hemodialysis on sleep apnea syndrome in end-stage renal disease. Clin Nephrol. 1990;33:247–251. MEDLINE [8]. [8]Stepanski E, Faber M, Zorick F, et al. Sleep disorders in patients on continuous ambulatory peritoneal dialysis. J Am Soc Nephrol. 1995;6:192–197. MEDLINE [9]. [9]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. MEDLINE [10]. [10]Beecroft J, Duffin J, Pierratos A, et al. Enhanced chemo-responsiveness in patients with sleep apnoea and end-stage renal disease. Eur Respir J. 2006;28:151–158. MEDLINE |
CrossRef
[11]. [11]Younes M, Ostrowski M, Thompson W, et al. Chemical control stability in patients with obstructive sleep apnea. Am J Respir Crit Care Med. 2001;163:1181–1190. [12]. [12]Javaheri S. A mechanism of central sleep apnea in patients with heart failure. N Engl J Med. 1999;341:949–954. MEDLINE |
CrossRef
[13]. [13]Lahiri S, Maret K, Sherpa MG. Dependence of high altitude sleep apnea on ventilatory sensitivity to hypoxia. Respir Physiol. 1983;52:281–301. MEDLINE |
CrossRef
[14]. [14]Xie A, Rutherford R, Rankin F, et al. Hypocapnia and increased ventilatory responsiveness in patients with idiopathic central sleep apnea. Am J Respir Crit Care Med. 1995;152:1950–1955. [15]. [15]Pierratos A. Daily nocturnal home hemodialysis. Kidney Int. 2004;65:1975–1986. MEDLINE |
CrossRef
[16]. [16]Hamilton RW, Epstein PE, Henderson LW, et al. Control of breathing in uremia: ventilatory response to CO2 after hemodialysis. J Appl Physiol. 1976;41:216–222. [17]. [17]Chan CT, Floras JS, Miller JA, et al. Regression of left ventricular hypertrophy after conversion to nocturnal hemodialysis. Kidney Int. 2002;61:2235–2239. MEDLINE |
CrossRef
[18]. [18]Solin P, Bergin P, Richardson M, et al. Influence of pulmonary capillary wedge pressure on central apnea in heart failure. Circulation. 1999;99:1574–1579. MEDLINE [19]. [19]Chan CT, Hanly P, Gabor J, et al. Impact of nocturnal hemodialysis on the variability of heart rate and duration of hypoxemia during sleep. Kidney Int. 2004;65:661–665. MEDLINE |
CrossRef
[20]. [20]Narkiewicz K, van de Borne P, Montano N, et al. Sympathetic neural outflow and chemoreflex sensitivity are related to spontaneous breathing rate in normal men. Hypertension. 2006;47:51–55.
CrossRef
[21]. [21]Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Los Angeles, CA: Brain Information Service/Brain Research Institute, UCLA, 1968 (NIH publication no. 204). [22]. [22]Jindal KK, Manuel A, Goldstein MB. Percent reduction in blood urea concentration during hemodialysis (PRU). A simple and accurate method to estimate Kt/V urea. ASAIO Trans. 1987;33:286–288. MEDLINE [23]. [23]Casey K, Duffin J, McAvoy GV. The effect of exercise on the central-chemoreceptor threshold in man. J Physiol. 1987;383:9–18. MEDLINE [24]. [24]Duffin J, McAvoy GV. The peripheral-chemoreceptor threshold to carbon dioxide in man. J Physiol. 1988;406:15–26. MEDLINE [25]. [25]Mohan R, Duffin J. The effect of hypoxia on the ventilatory response to carbon dioxide in man. Respir Physiol. 1997;108:101–115. MEDLINE |
CrossRef
[26]. [26]Read DJ. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med. 1967;16:20–32. MEDLINE [27]. [27]Duffin J, Mohan RM, Vasiliou P, et al. A model of the chemoreflex control of breathing in humans: model parameters measurement. Respir Physiol. 2000;120:13–26. MEDLINE |
CrossRef
[28]. [28]Skatrud JB, Dempsey JA. Interaction of sleep state and chemical stimuli in sustaining rhythmic ventilation. J Appl Physiol. 1983;55:813–822. MEDLINE [29]. [29]Khoo MC. Determinants of ventilatory instability and variability. Respir Physiol. 2000;122:167–182. MEDLINE |
CrossRef
[30]. [30]Warner G, Skatrud JB, Dempsey JA. Effect of hypoxia-induced periodic breathing on upper airway obstruction during sleep. J Appl Physiol. 1987;62:2201–2211. [31]. [31]Onal E, Burrows DL, Hart RH, et al. Induction of periodic breathing during sleep causes upper airway obstruction in humans. J Appl Physiol. 1986;61:1438–1443. [32]. [32]Hudgel DW, Chapman KR, Faulks C, et al. Changes in inspiratory muscle electrical activity and upper airway resistance during periodic breathing induced by hypoxia during sleep. Am Rev Respir Dis. 1987;135:899–906. MEDLINE [33]. [33]Narkiewicz K, Kato M, Pesek CA, et al. Human obesity is characterized by a selective potentiation of central chemoreflex sensitivity. Hypertension. 1999;33:1153–1158. [34]. [34]Oren A, Whipp BJ, Wasserman K. Effects of chronic acid–base changes on the rebreathing hypercapnic ventilatory response in man. Respiration. 1991;58:181–185. MEDLINE |
CrossRef
[35]. [35]Duffin J. Role of acid–base balance in the chemoreflex control of breathing. J Appl Physiol. 2005;99:2255–2265. [36]. [36]Pierratos A. Longer time dialysis: nocturnal dialysis. In: Henrich WL editors. Principles and practice of dialysis. 3rd ed.. Philadelphia, PA: Lippincott Williams & Wilkins; 2004;p. 137–146. [37]. [37]Schoene RD, Robertson HT, Pierson DJ, et al. Respiratory drives and exercise in menstrual cycles of athletic and nonathletic women. J Appl Physiol. 1981;50:1300–1305. MEDLINE [38]. [38]Holley JL, Schmidt RJ, Bender FH, et al. Gynecologic and reproductive issues in women on dialysis. Am J Kidney Dis. 1997;29:685–690. Abstract |
Full-Text PDF (598 KB)
|
CrossRef
[39]. [39]Joseph G, MacRae JM, Heidenheim AP, et al. Extravascular lung water and peripheral volume status in hemodialysis patients with and without a history of heart failure. ASAIO J. 2006;52:423–429. MEDLINE |
CrossRef
[40]. [40]Spiegel DM, Bashir K, Fisch B. Bioimpedance resistance ratios for the evaluation of dry weight in hemodialysis. Clin Nephrol. 2000;53:108–114. MEDLINE [41]. [41]Raj DS, Ouwendyk M, Francoeur R, et al. Beta(2)-microglobulin kinetics in nocturnal haemodialysis. Nephrol Dial Transplant. 2000;15:58–64. MEDLINE |
CrossRef
[42]. [42]Converse RL, Jacobsen TN, Toto RD, et al. Sympathetic overactivity in patients with chronic renal failure. N Engl J Med. 1992;327:1912–1918. MEDLINE [43]. [43]Guilleminault C, Bassiri A. Clinical features and evaluation of obstructive sleep apnea–hypopnea syndrome and the upper airway resistance syndrome. In: Kryger MH, Roth T, Dement WC editor. Principles and practices of sleep medicine. Philadelphia, PA: Elsevier Inc.; 2005;p. 1043–1052. [44]. [44]Beecroft JM, Hoffstein V, Pierratos A, et al. Nocturnal haemodialysis increases pharyngeal size in patients with sleep apnoea and end-stage renal disease. Nephrol Dial Transplant 2007; doi:10.1093/ndt/gfm598. a Department of Medicine, University of Calgary, 1421 HSC, 3330 Hospital Drive NW, Calgary, Alta., Canada T2N 4N1 b Department of Physiology, University of Toronto, Ont., Canada c Department of Medicine, Humber River Regional Hospital, Toronto, Ont., Canada d Department of Medicine, University of Toronto, Ont., Canada  Corresponding author. Tel.: +1 403 220 2865; fax: +1 403 283 6151.
PII: S1389-9457(07)00429-7 doi:10.1016/j.sleep.2007.11.017 © 2007 Elsevier B.V. All rights reserved. | |
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