Nocturnal PD Better for OSA Than CAPD

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Improvement in Sleep Apnea during Nocturnal PeritonealDialysis Is Associated with Reduced Airway Congestion andBetter Uremic Clearance

Sydney C. W. Tang,* Bing Lam, Andrew S. H. Lai, Clara B. Y. Pang, Wai Kuen Tso,

Pek Lan Khong, Mary S. M. Ip, and Kar Neng Lai**Division of Nephrology and Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong

and Queen Mary Hospital; and Department of Diagnostic Radiology, Queen Mary Hospital, Hong Kong, China

Background and objectives: Among peritoneal dialysis (PD) patients, nocturnal PD (NPD) is known to improve sleep apnea

compared with continuous ambulatory peritoneal dialysis (CAPD), but the contributing factors are unclear.

Design, setting, participants, and measurements: Thirty-eight incident ESRD patients underwent overnight polysomnog-

raphy (PSG) during NPD and CAPD. Bioelectrical impedance analysis, magnetic resonance imaging of the upper airway, and

urea kinetics (Kt/V) during sleep were measured on both occasions.

Results: The prevalence of severe sleep apnea (apnea-hypopnea index, AHI > 15/h) was 21.1% during NPD, and 42.1%

during CAPD. Mean AHI increased from 9.6 2.7/h during NPD to 21.5 4.2/h during CAPD. Both obstructive and central apnea

worsened after conversion to CAPD. NPD achieved greater reductions in total body water, hydration fraction, and net ultrafiltrationthan CAPD during sleep. Overnight peritoneal Kt/V and creatinine clearance were lower after conversion. Both peritoneal Kt/V and

peritoneal creatinine clearance correlated with AHI, as did their changes after conversion. Volumetric magnetic resonance imaging

revealed reduced pharyngeal volumes and cross-sectional area, and tongue enlargement after conversion.

Conclusions: Improvement in sleep apnea during NPD versus CAPD is associated with better fluid and uremic clearance

and reduced upper airway congestion during sleep.

Clin J Am Soc Nephrol 4: 410 418, 2009. doi: 10.2215/CJN.03520708

Sleep apnea has been reported in up to 50% to 70% of

patients with end-stage renal disease (ESRD) (1), a value at

least 10 times higher than the prevalence reported in the

general population (24). The pathogenesis of sleep apnea inpatients with ESRD remains unclear. Unruh et al. (5) recently

reported that patients on hemodialysis had a fourfold increase in

prevalence of sleep-disordered breathing and nocturnal hypox-

emia even after adjusting for cardiovascular morbidity and dia-

betic status, compared with participants from the Sleep Heart

Health Study matched for age, gender, body mass index, and race,

indicating that the pathophysiology of sleep apnea is uniquely

associated with the development of chronic renal failure. Previous

investigators have observed features of both central and obstruc-

tive sleep apnea (OSA) in patients with ESRD (610), which sug-

gest that its pathogenesis is related both to destabilization of

central respiratory control and upper airway occlusion. Moreover,

nocturnal hypoxemia is a strong predictor for incident cardiovas-

cular complications in the dialysis population (11).

Although sleep apnea is not corrected by conventional he-

modialysis or peritoneal dialysis (9,10), it has been reversed

both by nocturnal hemodialysis (7) and kidney transplantation

(6,8). Recently, we also reported improvement of sleep apnea

by nocturnal cycler-assisted peritoneal dialysis (NPD) com-

pared with conventional continuous ambulatory peritoneal di-alysis (CAPD) (12) through better fluid clearance during sleep.

However, a direct proof of whether a reduction in total body

water (TBW) content would alleviate airway occlusion is still

lacking. Furthermore, improved fluid removal per se remains an

inadequate explanation of why central sleep apnea is also im-

proved by NPD. In this study, we hypothesized that NPD, in

comparison to CAPD, promotes better fluid and solute clear-

ance during sleep and this may be associated with improve-

ments of both the obstructive and central components of sleep

apnea, respectively.

Materials and MethodsStudy Design

We performed a modified cross-over study. We made use of the fact that

in Hong Kong, all incident patients who required CAPD had to undergo,

after Tenckhoff catheter placement, a temporary period of mandatory

cycler-assisted NPD for approximately 8 wk while awaiting their turn for

CAPD training. Such a design circumvents the logistic difficulties in per-

forming cross-over studies in PD subjects caused by the inherent complex-

ity in establishing a patient on a particular system of NPD or CAPD, as

each system has its own hardware, dialysis solution, and connective

methodology, together with the possible training needed for the patient,

family member, helper to use the particular system. Consenting adult

subjects underwent one PSG study toward the end of their 6 to 8 wk of

Received July 16, 2008. Accepted October 29, 2008.

Published online ahead of print. Publication date available at www.cjasn.org.

Correspondence: Prof. Kar Neng Lai, Department of Medicine, Queen Mary

Hospital, 102 Pokfulam Road, Hong Kong SAR, China. Phone: 852-2855-4250; Fax:

852-2816-2863; E-mail: [email protected]

Copyright 2009 by the American Society of Nephrology ISSN: 1555-9041/4020410


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NPD treatment. They then underwent training for CAPD, and a second

PSG study was performed as soon as they had been established on stable

CAPD. All subjects had to have been deemed clinically euvolemic, with

serum sodium between 135 and 145 mmol/L on study entry and before

PSG. The study protocol was reviewed and approved by the Institutional

Review Board and Clinical Research Ethics Committee of the University of

Hong Kong, and all patients gave written informed consent to participate

in the study.

PatientsThe PSG data in 24 incident PD subjects and body water composition

data in 15 of these 24 subjects during NPD and CAPD were reported

previously (12). Here, we extended these data by recruiting another 22

incident patients to undergo PSG and magnetic resonance imaging

(MRI) of the upper airway during NPD and CAPD. Among them, 8

completed the first PSG and MRI study but declined to participate in

the second measurement, and their data were not included in the

analyses. The final number of patients with evaluable PSG data was 38,

of whom 14 were new. The final numbers of patients with evaluable

body water composition and MRI data were 29 and 14, respectively.

The underlying renal disease of the 38 patients (19 men; mean age,

54.2 13.3 y) were diabetes mellitus in 14, IgA nephropathy in four,membranous nephropathy in one, lupus nephritis in one, focal segmental

glomerulosclerosis in two, pauci-immune crescentic glomerulonephritis in

two, anti-GBM disease in one, polycystic kidney disease in two, and

unknown in 11. The average interval between the two sets of PSG record-

ings was 4.12 0.63 mo, and there was no appreciable change in residual

renal function, neck circumference, neck:height ratio, body mass index,

and other biophysical parameters over this period (Table 1).

PSGComprehensive overnight PSG was performed in hospital with the

Alice 3 or Alice 5 apparatus (Healthdyne, Atlanta, GA). All PSGs were

scored manually according to standard criteria by an independent

expert in sleep medicine who was unaware of the mode of dialysis (13).The average number of episodes of apnea and hypopnea per hour of

sleep (apnea-hypopnea index [AHI]) was calculated as the summary

measurement of sleep-disordered breathing.

Significant sleep apnea was defined as an AHI of 15 events per

hour of sleep. Apnea were classified as central if there was no chest and

abdominal movement, or as obstructive if chest and abdomen moved

paradoxically, and as mixed if an initial absence of ventilatory effort

was followed by an obstructive apnea pattern on resumption of effort.

For practical purposes, all hypopneic or mixed events were classified as

obstructive events.

Dialysis ProtocolDuring NPD, patients performed overnight exchanges of 10 to 12 L of

peritoneal dialysis fluid (PDF) at 2.0 to 2.2 L/cycle for 5 to 6 cycles by

means of an automated cycler (HomeChoice, Baxter Healthcare, Mc-

Gaw Park, IL). For CAPD, patients performed 3 to 4 daily exchanges of

2 L PDF using either the UltraBag (Baxter Healthcare, Guangzhou,

China), StaySafe or AndyDisk (Fresenius Medical Care, Bad Homburg,

Germany), or Gambrosol Trio (Gambro Lundia AB, Lund, Sweden)

system. The number of exchanges was clinically determined to achieve

euvolemia.

Residual Renal Function, Overnight Kt/V, and CreatinineClearance (CrCl) Assessment

Residual GFR was calculated according to the four-variable MDRD

equation at the point of Tenckhoff catheter placement (14). The ade-

quacy of dialysis indices were assessed by measuring total, peritoneal,

and renal Kt/V and CrCl. The peritoneal component (nightly peritoneal

Kt/V [pKt/V] and peritoneal CrCl [pCrCl]) was estimated solely fromthe overnight effluent dialysate on the night of PSG examination,

whereas the renal component was estimated from 24-h urine collection.

For nightly pKt/V and pCrCl during NPD, all spent dialysate

drained from the PD cycler was collected in a bucket. The volume of the

dialysate was accurately measured, and the dialysate was stirred vig-

orously before a representative aliquot was obtained for calculation of

urea and creatinine concentrations. Because NPD patients did not

undergo dialysis during the day, the nightly pKt/V and pCrCl was also

the 24-h pKt/V and pCrCl. Renal clearance was derived from 24-h

urine urea and creatinine divided by plasma urea and creatinine con-

centrations, respectively. The nightly renal component of Kt/V and

CrCl was estimated from the 24-h urine result normalized for time in

bed (24-h result time in bed in h/24 h).For nightly pKt/V and pCrCl during CAPD, the spent dialysate from

the overnight dwell of PDF was used for calculation of nightly clear-

ance in a fashion similar to that for NPD. For 24-h clearance, all spent

dialysate from day and night exchanges were used for calculation.

Renal clearance (24-h and nightly result) was estimated as stated above.

The crude body weight was used to calculate V according to the

method of Watson (15).

Table 1. Biophysical and clinical parameters while on NPD or CAPD (n 38)

Parameter On NPD On CAPD

Body mass index (kg/m2, abdomen emptied) 23.2 3.6 23.9 4.2Neck circumference (cm) 37.1 3.4 36.6 3.1Neck:height ratio 0.219 0.024 0.222 0.022Systolic blood pressure (mmHg) 133 16 131 17Diastolic blood pressure (mmHg) 83 10 86 12No. of antihypertensive drugs 2.4 0.68 2.3 0.54Hemoglobin (g/dl) 9.5 1.3 10.1 1.9Serum albumin (g/L) 34.8 4.9 34.5 3.7Plasma bicarbonate (mmol/L) 24.0 3.2 26.4 3.6Residual urine output (L/24 h) 0.88 0.13 0.84 0.10Residual GFR (ml/min/1.73 m2 BSA) 8.77 2.2 8.69 1.9

Data are presented as mean ( SD). P 0.05 for all comparisons during NPD or CAPD. GFR, glomerular filtration rate;BSA, body surface area.

Clin J Am Soc Nephrol 4: 410 418, 2009 NPD Improves SA via Fluid and Urea Removal 411


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Bioelectrical Impedance AnalysisBioelectrical impedance analysis (BIA) to assess body water compo-

sition using Nutrigard-M Bioelectrical Impedance Analyzer (Data Input

GmbH, Darmstadt, Germany) was performed on the night of PSG

before starting NPD or CAPD night dwell, and in the morning after

completing NPD or the CAPD night dwell, with the peritoneum emp-

tied. All measurements were made with the patient in the euvolemic

state, i.e., after the patients condition had become stabilized while they

were undergoing a particular mode of PD. Formulas for deriving bodywater compositions were described in our recent report (12).

Magnetic Resonance Imaging (MRI)Each patient underwent an MRI scan of the upper airway while

awake, within 6 h after completing NPD or the night dwell of CAPD.

The protocol was modified from that reported by Ryan et al. (16) Briefly,

the patients head was placed in a holding frame, and scans were

performed during tidal breathing using a GE MRI 3T scanner. Sagittal

and axial scans were acquired from T1-weighted images.

All MRI images were recorded digitally and interpreted by two

independent observers who were unaware of the patients mode of

dialysis. Five anatomical sites were measured (Figure 1) and were

defined as follows:(1) Nasopharynx was airway bordered by the soft palate anteriorly,

the nasal turbinates anteriorly and superiorly, and the adenoids poste-

riorly and superiorly. The inferior border was at the level of the inferior

tip of the uvula.

(2) Oropharynx was the aerated space bordered by the hard palate

superiorly, the tongue inferiorly, and the soft palate posteriorly.

(3) Hypopharynx was the aerated space bordered by the posterior

aspect of the tongue anteriorly, the posterior pharyngeal wall posteri-

orly, and the inferior aspect of the soft palate superiorly. The inferior

border was defined by the inferior extent of the base of the tongue.

(4) Minimal pharyngeal cross-sectional area was taken from the axial

slice at which the pharyngeal area was the smallest.

(5) Volume of the tongue measured on sagittal images with axialcorrelation.

Volume measurements were then calculated on the basis of the

sagittal areas of a series of contiguous slices and on the thickness of the

scan slices.

Statistical AnalysesData were expressed as means SD unless otherwise specified.

Statistical analyses were performed using SPSS for Windows software

version 14.0 (Statistical Package for the Social Sciences Inc., Chicago,

IL). Comparisons between groups were performed by 2 test for cate-

gorical data, and Mann-Whitney Utest for continuous data. Because of

individual variations in the volumetric analyses of the upper airway

parameters as shown on MRI, all numeric changes were expressed as

percentage variation with respect to values obtained during NPD.

Nonparametric paired-sample Wilcoxon signed rank test was used to

determine changes in sleep disturbance parameters, nightly and 24-h

Kt/V and creatinine clearances, and volumetric measurements on MRI

studies during NPD and CAPD. Comparison of within-group differ-

ences in prevalence of sleep apnea during NPD or CAPD was per-

formed using the McNemar test. Relationships between absolute or

differential nightly pKt/V or pCrCl and AHI were analyzed using

Spearman rank correlation. A P value of 0.05 was considered signif-

icant. All probabilities were two-tailed.

ResultsThe prevalence of sleep apnea (AHI 15/h) was 21.1% (n

8) during NPD and 42.1% (n 16) during CAPD (Table 2).

Figure 1. Anatomic demarcations of the predefined landmarks(see text for definition) of the upper airway illustrated by MRI.(A) Representative sagittal image showing the anatomic bound-aries for measuring the areas of the oropharynx (1), tongue (2),nasopharynx (3), and hypopharynx (4). The corresponding vol-umes were then calculated on the basis of the sagittal areas ofa series of contiguous slices and on the thickness of the scanslices. (B) Representative axial image showing the slice at whichthe pharyngeal area was the smallest (1) among contiguousaxial slices of the pharynx.

412 Clinical Journal of the American Society of Nephrology Clin J Am Soc Nephrol 4: 410 418, 2009


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When the AHI cutoff was lowered to 10/h, the prevalence was

26.3% (n 10) during NPD, and 50% (n 19) during CAPD. As

a group, the absolute AHI values increased from 9.6 2.7/h

during NPD to 21.5 4.2/h during CAPD (P 0.001 for

comparison before and after transfer to CAPD). Both obstruc-

tive and central components of sleep apnea became signifi-

cantly more severe, and the individual changes in AHI values

during the two different modes of PD are shown in Figure 2.

The overall sleep pattern during NPD or CAPD was summa-

rized in Table 2. Although there was no significant difference in

the total sleep time during NPD or CAPD, the duration of sleepwith hypoxia (oxygen saturation 90%) was substantially

longer during CAPD (P 0.025). In addition, there were sig-

nificantly more frequent arousals after conversion to CAPD

(P 0.001).

Multifrequency BIA revealed no difference in absolute body

water content before NPD or the night dwell of CAPD (Figure

3), alleviating concerns that there may be significant change in

body water composition in the brief interval between NPD and

CAPD. Applying BIA just before and after NPD or the night

dwell of CAPD to calculate the change in body fluid composi-

tion during sleep, NPD achieved a significantly larger volume

of fluid removal, as reflected by greater reductions in absolute

body water contents (Figure 4A). Compared with CAPD, NPD

led to a 2.2-fold (P 0.003), 1.9-fold (P 0.005), and 1.6-fold

(P 0.003) more intense reduction in total body water, extra-

cellular body water, and intracellular body water, respectively,

during sleep. When total body water was expressed as hydra-

tion fraction (percentage of body weight due to water only),

there was a sixfold difference in reduction achieved by NPD

versus CAPD (3.77 0.49 versus 0.62 0.41%, P 0.001).

Similarly, the percentage change in hydration before and after

NPD or CAPD was also significantly higher in the former (P

0.001) (Figure 4B).

Volumetric MRI measurements showed that there were sig-

nificant reductions in the nasopharyngeal (24.5 9.6%) and

oropharyngeal (34.0 11.6%) volumes, minimal pharyngeal

cross-sectional area (16.8 4.7%), and increase in tongue

volume (8.22 2.4%) after conversion from NPD to CAPD

(Figure 5). There were also numerical reductions in the hypo-

pharyngeal volume (21.6 11.9%), albeit not reaching statis-

tical significance. When the contiguous volumes of the naso-,

oro-, and hypopharynxes were examined in aggregate, there

was a 30.8 9.2% reduction (P 0.004) after conversion. The

reduction in this aggregate volume also correlated with the

change in the indices of obstructive sleep apnea (r 0.565,

P

0.035).Urea kinetics analyses of the overnight spent dialysate dur-

ing the night of PSG examination revealed that nightly pKt/V

and pCrCl were both significantly higher during NPD than

CAPD (pKt/V: 0.289 0.070 versus 0.065 0.023 per night, P

0.001; pCrCl: 4.87 1.22 versus 1.84 0.67 L per night, P

0.001) (Figure 6). The difference in nocturnal clearance between

NPD and CAPD remained significant (total Kt/V: 0.338 0.078

versus 0.118 0.051 per night, P 0.001; total CrCl: 6.42 1.50

versus 3.22 1.20 L per night, P 0.001) even after taking into

account the estimated endogenous component of Kt/V and

CrCl that was derived from 24-h urine and normalized against

the time in bed for each patient (Table 3). To further substan-

tiate the impact of peritoneal clearance on sleep apnea, we

examined the relationship between overnight pKt/V or pCrCl

and AHI in all subjects during NPD and CAPD. There were

significant negative correlations between pKt/V and AHI (r

0.332, P 0.003), and between pCrCl and AHI (r 0.319,

P 0.005). The difference in overnight pKt/V or pCrCl be-

tween each mode of PD was significantly correlated with the

difference in AHI for each individual patient (Figure 7).

DiscussionWe have extended our fixed intervention study cohort to

investigate the mechanisms through which NPD improves

sleep apnea compared with CAPD. Our results reaffirmed a

Table 2. Polysomnographic data while on NPD or CAPD (n 38)

On NPD On CAPD P

Total sleep time (h) 5.0 1.60 5.55 1.41 NSSleep efficiencya 57.4 14.4 62.8 12.7 NSStage of sleep (% of total sleep time)

rapid eye movement 18.2 10.5 16.7 8.6 NS

stage 1, 2 78.8 22.1 79.3 20.0 NSslow wave (stage 3, 4) 1.9 3.2 4.0 3.6 NS

AHI (no./h) 9.6 2.74 21.5 4.15 0.001subjects with AHI 15 (n, %) 8 (21.1%) 16 (42.1%) 0.008subjects with AHI 10 (n, %) 10 (26.3%) 19 (50%) 0.004subjects with AHI 5 (n, %) 11 (28.9%) 22 (57.9%) 0.001

Duration with oxygen saturation 90% (min) 64.3 15.8 94.8 20.5 0.025Arousals (no./h) 16.6 9.8 26.6 16.4 0.001Periodic leg movement (no./h) 0.5 0.21 1.4 0.35 0.007

aRatio of total sleep time to total time in bed. Data are presented as mean ( SD). AHI, apnea-hypopnea index (i.e., averagenumber of episodes of apnea and hypopnea per hour of sleep).



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significant worsening of sleep apnea after conversion from

NPD to CAPD, as reflected by substantial increases in AHI,

increased prevalence of sleep apnea, prolongation of the dura-

tion of hypoxia, and more frequent arousals during sleep. On a

mechanistic basis, we showed that a major component that

alleviated the severity of sleep apnea during NPD in compar-

ison to CAPD was more intensive ultrafiltration, which led to

larger reductions in total body water and hydration fractionduring sleep, as indicated by BIA measurements. This may

translate indirectly to reduced airway edema and therefore less

severe OSA.

Here, we performed MRI of the upper airway to detect any

subtle changes in the airway during each of the two modes of

PD. Volumetric MRI is a powerful tool for detecting changes in

these structures (17). A practical disadvantage of MRI is pa-

tient-perceived discomfort and claustrophobia. A considerable

proportion (up to 36%) of patients in this study, having under-

gone the first MRI, declined to undergo a second.

Among patients who underwent MRI during NPD and

CAPD, there were reduced aggregate pharyngeal volumes and

Figure 2. Individual changes in overall apnea-hypopnea index (A), obstructive apnea index (B), and central apnea index (C) in 38subjects during NPD and after conversion to CAPD. Horizontal bars represent mean SEM values during each mode of PD. P 0.001 compared with values while on NPD.

Figure 3. Absolute body water composition before NPD (open bars)or the overnight dwell of CAPD (solid bars) using bioelectrical im-pedance analyses (n 29). Error bars are mean SD. TBW, totalbody water; ECW, extracellular water; ICW, intracellular water.



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minimal pharyngeal cross-sectional area, together with con-

comitant increase in tongue volume after switching from NPD

to CAPD. Tongue enlargement may also represent fluid accu-

mulation in other soft tissues bordering the airway such as the

nuchal and peripharyngeal areas, which are difficult to assess

in an objective manner because of the lack of clear-cut anatom-

ical demarcations. It is conceivable that such anatomic alter-

ations favoring narrowing of the upper airway may give rise to

OSA during sleep in predisposed patients when there is a

reduced tone of the supporting airway musculature. This is

evidenced by the correlation between the reduction in the

aggregate pharyngeal volume and the worsening of the ob-

structive component of sleep apnea after conversion to CAPD.

Furthermore, it is envisaged that fluid accumulation in the

upper airway will increase airflow resistance of the pharynx, as

reflected by the decrease in minimal pharyngeal cross-sectional

area on switching to CAPD. In support of this notion, Chiu et al.

(18) recently applied lower body positive pressure using anti-

shock trousers to displace fluid from the legs to the upper body,

and found that the maneuver resulted in increased pharyngeal

airflow resistance. Beecroft et al. (19) recently showed that

pharyngeal narrowing contributes to the pathogenesis of OSA

in dialysis-dependent patients. Furthermore, in patients con-

verted from conventional to nocturnal hemodialysis, there was

an increase in pharyngeal size together with improvement in

sleep apnea (20). This study is the first to show a reduction in

airway diameter on conversion from NPD to CAPD.

Apart from improving OSA, our data showed that NPD also

improved the central component of sleep apnea. It remains un-

clear why a modality switch that principally affects fluid balance

Figure 4. Changes in body water composition during sleep after

NPD (open bars) or the overnight dwell of CAPD (solid bars)using bioelectrical impedance analyses (n 29). (A) Absolutechanges in total body water (TBW), extracellular water (ECW),and intracellular water (ICW), calculated by the difference in theabsolute body water content before and after each mode of PDwhich reflects the net fluid loss during sleep. (B) Changes inhydration fraction (TBW [in liters]/body weight [in kilograms] 100%) and percentage changes in hydration fraction (postdialyticminus predialytic hydration fraction/predialytic hydration frac-tion) before and after each mode of PD, which reflects the net fluidshifts during sleep. Error bars are mean SEM.

Figure 5. Percentage volumetric change in the various anatomicsites of the upper airway after conversion to CAPD (n 14).*P 0.004, P 0.04, P 0.02 versus values obtained duringNPD. NP, nasopharynx; OP, oropharynx; HP, hypopharynx;MPXA, minimal pharyngeal cross-sectional area. Error bars aremean SEM.

Figure 6. Absolute peritoneal solute clearance during sleep.Kt/V and CrCl that was derived from the overnight effluentduring NPD or CAPD for each patient was computed. Stippledand hatched bars represent overnight pKt/V and pCrCl, re-spectively. pKt/V, peritoneal Kt/V; pCrCl, peritoneal creati-nine clearance.



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and airway patency, and hence resistance, should affect central

sleep apnea. One possible explanation, learned from cross-over

studies in hemodialysis subjects (7), is through correction of met-

abolic acidosis and hypocapnia using nocturnal hemodialysis. The

attenuation of hypocapnia may then disinhibit the central respi-

ratory center that became suppressed in the face of hypocapnia.

However, this is not a likely explanation for NPD, which is a

biochemically modest procedure compared with HD in terms of

acidosis correction, as reflected by similar serum bicarbonate lev-

els during NPD or CAPD. An alternative mechanism that we

contemplated was a difference in the rate of removal of uremic

waste products. Because residual renal function remained un-

changed during NPD or CAPD, we focused on the peritoneal

component of solute clearance during sleep and calculated the

nightly Kt/V and CrCl contributed solely by PD during sleep. The

only demonstrated difference between NPD and CAPD, apart

from fluid status, was the much higher nightly pKt/V and pCrCl

during NPD, which could represent a circumstantial evidence of

the effect of uremic toxins on sleep apnea. Even after taking into

account the estimated contribution of endogenous clearance dur-

ing the night, the total nighttime clearance was still significantly

higher during NPD than during CAPD. Although it could be

argued that the daytime component of CAPD that has to be

significantly higher than that of NPD could lead to a better status

at the beginning of sleep, several lines of evidence suggest that

nocturnal clearance plays a more important role: (1) the negative

correlation between absolute pKt/V and pCrCl with AHI values;

(2) the correlation between the decrease in pKt/V and pCrCl with

the rise in AHI on conversion from NPD to CAPD; (3) patients

who underwent conventional hemodialysis that had to confer a

significantly higher daytime clearance than that of nocturnal he-

modialysis still had significantly worse sleep apnea during day-

time versus nocturnal hemodialysis (7); and (4) the decrease in

chemoreflex responsiveness to carbon dioxide after conversion

from conventional to nocturnal hemodialysis, which is associated

with increased uremic clearance during sleep (21).

There are several limitations to this study. First, we did not

measure airway pressure and pharyngeal resistance, because it

Table 3. Dialysis-related parameters while on NPD or CAPD (n 38)

Parameter On NPD On CAPD P

24-h Kt/Vtotal 0.427 0.101 0.358 0.097 0.001peritoneala 0.289 0.070 0.207 0.071 0.001renalb 0.138 0.062 0.151 0.121 0.908

24-h CrCl (L)total 9.20 2.64 8.32 2.01 0.024peritoneala 4.87 1.22 4.36 1.16 0.069renalb 4.33 2.38 3.96 2.51 0.233

Nightly Kt/V (time in bed), Ltotal 0.338 0.078 0.118 0.051 0.001peritonealc 0.289 0.070 0.065 0.023 0.001renald 0.049 0.023 0.053 0.043 0.523

Nightly CrCl (time in bed), Ltotal 6.42 1.50 3.22 1.20 0.001peritonealc 4.87 1.22 1.84 0.67 0.001renald 1.55 0.89 1.38 0.91 0.179

Net ultrafiltration (ml per night) 1,729 799 (range, 170 to 3,053) 394 315 (range, 100 to 1,050) 0.001Body weight (kg)

night before PSG 56.2 9.8 56.8 10.8 0.084morning after PSG 54.1 9.7 56.0 10.6 0.001% change 3.7 1.7% 1.4 1.1% 0.001

Peritoneal transport statuse

overall D/PCr at 4 h (n, %) N/A 0.66 0.093low 0low average 21 (55.2%)high average 13 (34.2%)high 4 (10.5%)

Data are presented as mean ( SD).aBased on overnight peritoneal effluent for NPD and 24-h effluent for CAPD.bBased on 24-h urine collection.cBased on overnight peritoneal effluent.dEstimation based on 24-h result time in bed (h) /24 h.eAccording to the method of peritoneal equilibration test and classification of transport status by Twardowski (31).



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induces too much discomfort in a patient undergoing CAPD

and PSG monitoring to place another two catheter transducers

at the naso/hypopharynxes and a tightly fitting face mask for

flow recording during the same night (18). Second, the number

of subjects is small. It was difficult to recruit subjects to un-

dergo PSG and MRI in succession on two occasions, as reflected

by the high drop-out rate among consenting subjects. Third,

our results suggest, but do not directly prove, that better noc-

turnal clearance improves apnea. To achieve this goal will

require adding day exchanges to the NPD phase to match the

daytime clearance during the subsequent CAPD phase, which

was not feasible in our institutional setting. Likewise, reduced

airway congestion on NPD, as shown on MRI, provides only

circumstantial evidence that this is linked to improved sleep

apnea. Nevertheless, this contention is supported by the close

association between airway edema and sleep apnea (2225).

Finally, we have not studied the changes in intraperitoneal

pressure and the correlation with oxygen saturation. This arises

mainly from our concern with introducing a potential source of

contamination during PD caused by extra manipulation and

connection to a pressure transducer for continuous pressure

recording (26). Nevertheless, time-averaged intraperitoneal

pressure may be higher during CAPD than during NPD be-

cause of the permanent load of peritoneal dialysate during thenight in CAPD. Theoretically, this may have two effects: (1)

changes in respiratory mechanics, such as reduction in vital

capacity (27), although recent studies showed that sleep apnea

is unrelated to pulmonary function measurements [12,28] and

that flow-volume curve indices have no value in predicting

sleep apnea (29); (2) more pressure effect on the diaphragm. To

maintain the same tidal volume, a more negative intrathoracic

pressure has to be generated, which may cause arousal and

airway collapsibility, which could in turn lead to sleep apnea.

Determining whether the difference in intraperitoneal pressure

during CAPD and NPD causes a large enough change in in-

trathoracic pressure to bring about worsening of sleep apnea isbeyond the scope of the present study.

In conclusion, our results suggest that while many factors

including body habitus, comorbidities, and psychosocial cir-

cumstances (30) contribute to the development sleep apnea in

patients with chronic renal failure, fluid status and solute clear-

ance rates may be associated with the development of sleep

apnea in PD patients (Figure 8).

AcknowledgmentsThis study is supported by the Seed Funding Programme for Basic

Research of the University of Hong Kong. The authors are grateful to

Agnes Lai and Barbara Law (Sleep Laboratory), Sandra Luen (Division

of Nephrology), Helena Leung and all nursing staff (K18N Dialysis

Figure 7. Correlation between the difference in overnight pKt/V(A) or pCrCl (B) and the change in AHI following conversionfrom NPD to CAPD. pKt/V, peritoneal Kt/V; pCrCl, peritonealcreatinine clearance; AHI, apnea-hypopnea index.

Figure 8. Postulated pathophysiologic pathways leading tosleep apnea in chronic renal failure. Volume overloaded statuscauses redistribution of body water during the recumbent pos-ture and gives rise to upper airway congestion as evidenced byreduced pharyngeal luminal volumes, pharyngeal narrowing,and tongue enlargement, leading predominantly to obstructivesleep apnea. Accumulation of uremic toxins induces metabolicacidosis and hypocapnia and increases chemosensitivity to car-bon dioxide, leading predominantly to central sleep apnea.

Other comorbid conditions and body habitus also play anadjuvant role. Nocturnal dialysis or renal transplantation mayalleviate volume and uremic burdens and hence improve sleepapnea. Solid arrows, enhancing effect; interrupted arrows, in-hibitory effect. NPD, nocturnal peritoneal dialysis; NHD, noc-turnal hemodialysis; RTx, renal transplantation



9/9

Unit) for coordinating the PSG and MRI studies; Jack Lam (Sleep

Laboratory) for scoring all PSGs manually; Kan Ming Lo (Sleep Labo-

ratory) for performing all BIA measurements; and Suki Ho (Dialysis

Unit) for performing all urea kinetics computation.

DisclosuresNone.

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Nocturnal PD Better for OSA Than CAPD