NDT Advance Access originally published online on May 23, 2006
Nephrology Dialysis Transplantation 2006 21(9):2529-2535; doi:10.1093/ndt/gfl256
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Dialysis and Transplantation
Effect of short daily home haemodialysis on quality of life, cognitive functioning and the electroencephalogram
1 Dianet Dialysis Centres, University Medical Centre Utrecht, Utrecht, The Netherlands, 2 UMCU: Department of Nephrology and Hypertension, 3 UMCU: Department of Neuropsychology (WKZ), 4 UMCU: Department of Psychiatry, Rudolph Magnus Institute of Neuroscience and 5 UMCU: Department of Neurophysiology, University Medical Centre, Utrecht, The Netherlands
Correspondence and offprint requests to: Pieter F. Vos, Dianet Dialysis Centres Utrecht, Brennerbaan 130, 3524 BN Utrecht, The Netherlands. Email: p.vos{at}dianet.nl
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Abstract |
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Background. End-stage renal disease patients have a poor quality of life (QoL), suffer from impaired cognitive functioning, and their electroencephalogram (EEG) shows abnormalities. Conventional haemodialysis (CHD) only partially restores these disorders. Short daily haemodialysis (SDHD) has been reported to improve QoL, but effects on cognitive functioning and EEG have yet to be described.
Methods. Of the 13 patients (11 male, 2 female, age 45.5 ± 8.1 years), 11 completed the Kidney Disease Quality of Life and Affect Balance Scale questionnaires, 10 underwent neuropsychological testing, and all 13 underwent EEG examination. For the neuropsychological assessments, nine patients (six male, three female, age 45.4 ± 12.6) who remained on the CHD schedule, served as controls. The dialysis schedule of thrice-a-week for 4 h was changed in the experimental group to six times a week for 2 h (SDHD) over a period of 6 months and back to thrice a week for 4 h.
Results. When on SDHD, patients rated several dimensions of health-related QoL as being improved. After resuming CHD, one of these dimensions again decreased and several others worsened even lower than baseline. Cognitive functioning did not change when compared with control data. On the EEG, alpha peak frequency increased slightly when on SDHD but decreased significantly after resuming CHD.
Conclusions. SDHD improves health-related QoL, but has no clear effects on cognitive functioning and EEG. Resumption of CHD after SDHD decreases aspects of QoL and EEG alpha peak frequency but has no effect on cognitive functioning.
Keywords: cognitive functioning; electroencephalogram; end-stage renal disease; quality of life; short daily haemodialysis
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Introduction |
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Patients with end-stage renal disease (ESRD) have a poor quality of life (QoL) [1] and suffer from impaired cognitive functioning [2,3]. The latter, e.g. memory, attention, concentration and information processing, may be related to disturbed brain function [3,4–6], and psychological factors, e.g. depression, due to ESRD and renal replacement therapy [1].
The cause of brain function impairment is complex [7]. Among the explanatory factors are impaired oxygen metabolism due to cerebrovascular or brain cell derangements [7] and anaemia [5].
The brain function impairment is electrophysiologically characterized by a decrease in alpha peak frequency vs an increase in the lower (theta and delta) frequencies on the quantitative electroencephalogram (qEEG) and increased latency time of event-related potentials [3,5].
In a series of studies by our team concerning the brain function impairment in hypoxia/ischaemia, the decrease in alpha peak frequency appears to be one of the most subtle signs of brain function impairment [8].
Thrice weekly conventional haemodialysis (CHD), although a life-saving procedure for patients with ESRD, is still far from perfect despite many technical improvements in the past decades. It resolves the uraemic syndrome only partially, is complicated by high morbidity and mortality and does not result in an optimal QoL [1,9].
Options to improve neurophysiological and cognitive functioning may include a higher dialysis dose [4], a higher haematocrit through treatment with erythropoietin [5] and kidney transplantation [6].
Continuous ambulant peritoneal dialysis (CAPD), has been reported to have a greater potential to reverse uraemic encephalopathy than haemodialysis. This is hardly related to serum urea and creatinine concentrations [10], although this result is not found in all studies [3]. The superior effect of CAPD might be explained by the continuous aspect of this treatment resulting in stable fluid and plasma solute concentrations, or to the better ‘middle-molecule’ clearance through this dialysis modality.
Short daily home haemodialysis (SDHD), a more physiological treatment than a thrice-weekly CHD, has been reported to have beneficial effects on blood pressure, various metabolic variables and QoL [11,12]. The improvement in health-related QoL (HrQoL) is presumably related to less severe uraemic symptoms due to better haemodynamic and metabolic control.
Whether the effect of SDHD on electrophysiological and cognitive disturbances differs from that of CHD, is not yet known. If SDHD has a positive effect on these disturbances, it may contribute to the improvement in HrQoL.
We therefore used an a-b-a design to investigate the effect of SDHD on the EEG and cognitive functioning together with QoL in ESRD patients who were on a conventional thrice-a-week dialysis schedule.
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Patients and methods |
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Patient selection
All patients, who were being treated with conventional thrice-weekly home haemodialysis under supervision by our centre in April 1999, or who were referred to our dialysis centre for training for home haemodialysis between April/June 1999 and October 2000, were asked to participate in the study. Patients with diabetes mellitus and malignant diseases were excluded from the study.
Out of a total of 56 candidates, 17 agreed to enter the SDHD programme and to participate in the study. Of these patients, one withdrew, two died (from myocardial infarction and septicaemia) and one received a kidney transplant before the completion of the SDHD phase. Eventually, 13 patients aged between 38 and 60 years were included in the study (Table 1). Patients had been treated with haemodialysis for at least 12 months prior to inclusion.
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Ten patients participated in all three parts of the study, i.e. HrQoL, EEG and neuropsychological assessment, 11 patients completed the HrQoL-questionnaires and all underwent EEG-recording.
A control group of 11 patients, who remained on conventional thrice-weekly dialysis during the study period, but of whom two patients withdrew after the first assessment, was created for the neuropsychological investigation. Groups were matched for age and gender (Table 2).
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Study protocol
The study protocol was approved by the hospital ethical committee.
All patients gave their written informed consent after the study had been fully explained to them.
Patients, in both the experimental and control groups, were studied at baseline, while treated with thrice weekly CHD, after 6 months of six-times-a-week SDHD and again after 2 months of thrice-weekly CHD.
The tests were carried out 24 h after the previous dialysis session; in the case of SDHD, this meant that tests were done immediately before the next dialysis session.
Urea kinetics
Single pool Kt/V (spKt/V) was calculated according to Daugirdas [13].
Standard Kt/V (stdKt/V) was calculated according to Gotch [14].
Quality of life
Health-related QoL was measured using the Kidney Disease Quality of life (KDQoL) questionnaire, consisting of the Short Form-36 (SF-36) and a list of items concerning kidney disease and dialysis [15]. The clinimetric properties of the KDQoL are good and the dialysis-targeted dimensions in particular have been established to have a high reliability and validity [16]. Moreover, we administered the Affect Balance Scale questionnaire [17]. In addition to the SF-36-Physical and -Mental Summary Scores, KDQoL dimension scores were calculated according to Bakewell et al. [18].
Neuropsychological studies
A comprehensive neuropsychological assessment was performed 24 h after the previous dialysis session (Table 3).
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EEG
The 21-channel-EEGs were recorded during standard conditions (rest, hyperventilation, photostimulation, eyes open, eyes closed). Spectral analysis was performed during the eyes open and eyes closed conditions. Spectral precision was 0.2 Hz. Peak frequency of the alpha peak in the spectrum in the eyes closed condition was determined according to the method described by Vriens et al. [8].
Data management and statistical analysis
Urea kinetics, quality of life and EEG
Statistical analyses were carried out using SigmaStat for Windows version 2.03 (SSPS Inc.).
Differences between paired data, i.e. obtained during two study periods, were tested by paired Student's t-test.
Data were subjected to a one-way analysis of variance for repeated measures (ANOVA-1-RM), followed by Student–Newman-Keuls tests for post–hoc analysis.
Urea kinetic variables obtained from the experimental and control patient groups were analysed by a two-way ANOVA, followed by Student–Newman-Keuls tests for post-hoc analysis.
Statistical significance was defined as P < 0.05 (two-sided).
Neuropsychological assessments
Statistical analyses were carried out using the Statistical Package for the Social Sciences (SSPS version 9.0 for Windows). All test scores were rescaled to z-scores, computed using the means and the SDs of the group of patients who completed the first neuropsychological assessment (n = 28) as norm scores. Next, for each assessment, the test data were reduced to four summary measures by averaging the z-scores presumed to assess a similar functional domain. This resulted in four domains: speed of information processing, memory, executive functioning and attention (Table 3). Repeated measures analyses with one between-factor (domain score, i.e. score on a functional domain obtained in the three successive assessments) were used to analyse the functional domain scores over time for the experimental and control groups.
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Results |
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Urea kinetics
The spKt/V increased significantly in the experimental group in the SDHD phase, whereas it did not change in the control group (Table 4). In the SDHD phase, it was significantly higher compared with the control group, whereas it did not differ in either CHD-period. The stdKt/V also increased significantly in the SDHD patients, but was not significantly different from the control group in any phase of the study.
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Changes in quality of life
The data are summarized in Table 5. Before transfer to SDHD, patients scored remarkably low on the physical components of the SF-36 (except for bodily pain), whereas the mental components were far less compromised.
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SDHD significantly improved ‘general health perception’, a single item of the KDQoL questionnaire, as well as the KDQoL dimension scores ‘physical health’ and ‘patient satisfaction’, although the separate KDQoL items did not themselves improve significantly (only the SF-36 data are given in Table 5). Nor did mental and social items change significantly.
After resumption of CHD, patients not only experienced a deterioration of ‘general health perception’ and a worsening of the physical health summary score, but the ratings also indicated a decline in ‘role functioning (physical)’, and ‘vitality’. ‘Sleep’ (data not presented in Table 5) decreased significantly from 60 ± 11% to 45 ± 17%. During the first CHD period, patients rated ‘sleep’ as 56 ± 22% (NS). Patients’ satisfaction decreased as well, but not significantly.
The Affect Balance Scale index of well-being, and overall life satisfaction did not change significantly when patients were on SDHD. Nor was sexual activity altered by SDHD.
Neuropsychological changes
Groups were comparable with respect to sex, handedness, age, education level and non-verbal intelligence at the time of the first neuropsychological assessment (Table 2).
Changes in the four domains are presented for experimental and control subjects in Figure 1.
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Repeated measures analysis revealed a non-significant group x domain score interaction for each of the four functional domains. This indicates that tendencies to change in the four domains were the same for the experimental and control groups, i.e. SDHD neither improved nor reduced cognitive functioning in comparison with CHD.
Changes in the electroencephalogram
Transfer to SDHD produced a slight, not statistically significant, increase in the alpha peak frequency of the EEG-recordings (CHD1: 9.7 ± 0.9, SDHD: 9.8 ± 1.1). Two months after resumption of CHD there was a significant decrease in alpha peak frequency (9.3 ± 1.0, P < 0.05) (Figure 2), indicating a slight deterioration.
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Discussion |
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TopAbstractIntroductionPatients and methodsResultsDiscussionReferences |
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This study investigated the effects of SDHD on HrQoL, cognitive functioning and on the EEG in ESRD patients who were treated by CHD. It showed that SDHD improved general health perception and the perception of physical health when assessed by means of disease-specific scales (KDQoL), but did not have a clear effect on either cognitive functioning or the alpha peak frequency (EEG).
Resumption of CHD after 6 months did, however, have a deteriorating effect on the QoL together with a decrease in the electroencephalographically recorded alpha peak frequency, but had no consequences for cognitive functioning.
QoL questionnaires showed a significant improvement in ‘general health perception’ and in the disease-specific physical health dimension score (KDQoL). Single domains concerning physical health did not change significantly nor did mental and social items. These outcomes differ from those of our previous study [12], where we found improvements in both physical and mental functioning. This difference may be related to the small groups of patients studied. The failure to detect a significant change in either ‘mental health’ or the mental component summary score is probably due to the fact that ‘mental health’ in the currently investigated group of patients was (almost) as good as in the general, healthy Dutch population [9]. Moreover, other studies also showed that the dialysis mode has less of an effect on mental than on physical domains [1,9].
It is noteworthy, though not very surprising, that shortly after the discontinuation of SDHD, QoL declines considerably in various domains. ‘Role functioning (physical)’ deteriorated even to the level of incident dialysis patients [1]. Probably, patients need some time to get used to a new dialysis regime. They were apparently in balance physically and mentally at baseline, and after 6 months of SDHD, but not after resuming CHD. How the results would have been at the end of the second CHD period, if tests were scheduled after 6 months, is a matter of speculation. The patients could have either become reaccustomed to CHD, and feel subjectively better, or their physical and mental condition could have declined further due to this less physiological dialysis modality, and therefore, the test results could have worsened. However that may be, quite a few patients could hardly endure a second period of CHD longer than 2 months, so that we could not plan this study period later.
Neuropsychological investigations revealed neither a benefit nor a disadvantage of SDHD when compared with CHD. Even restarting CHD, resulting in a worse QoL, and leading to a slowing of the alpha-peak frequency, did not significantly affect cognitive functioning. Probably the group and/or the effect was too small to detect significant differences. It was, however, impossible to collect more patients suitable for this study. The increase in scores on the domains of memory, executive functioning and attention can be taken to indicate that the groups did not benefit differently in practice. Depression may have negatively influenced the outcome of neuropsychological testing, but QoL results did not indicate an increase in depression during SDHD.
It is known that conventional dialysis improves various cognitive variables in comparison with the pre-dialysis phase [2], and that optimal dialysis does not restore neuropsychological deficits completely [10]. High dialysis dose or high flux dialysis was no more effective than standard dose conventional dialysis [19], although CAPD may have a greater effect than haemodialysis [10]. These observations suggest that a certain critical dialysis dose is required to improve predialysis cognitive functioning, but that increasing dialysis dose beyond the standard levels is hardly more effective. In this respect, SDHD does not seem advantageous, either.
Treating patients with SDHD for 6 months had no significant effect on the alpha peak frequency, but resumption of CHD had a significant negative effect on this peak frequency. Chronic renal failure is associated with slowing of EEG frequencies with a decrease in alpha and an increase in theta rhythm [7]. Dialysis improves this abnormal EEG pattern [4], although abnormalities may persist [3]. Probably, SDHD offers no additional beneficial effect in the patients treated adequately with CHD over a longer period of time. This can also be deduced from the fact that acute, marked changes in uraemic toxin concentrations lead to considerable cerebral dysfunction, whereas slow progressive changes are less harmful, presumably because the brain has time to adapt [7]. In this regard, the resumption of CHD may have the effect of acute under-dialysis, leading to more overt uraemic symptoms and slowing of EEG frequencies. This is in accordance with the finding by Teschan et al. [4], who observed most EEG abnormalities in conditions of higher urea concentrations in National Cooperative Dialysis Study (NCDS) groups II and IV within 6 weeks after the start of the NCDS. Changes in haematocrit may also affect cerebral function [5], but since the haematocrit did not change significantly, this offers no explanation in the current situation.
The design of the present study gives reason for various points of concern. First, the number of patients was limited, but, as we have mentioned above, we were not able to include more patients, let alone do a randomized controlled-trial.
Second, the timing of the tests in relation to the dialysis sessions may have had an effect on the outcome. Cognitive functioning may have been affected by magnitude and rate of changes during the dialysis procedure itself and the interdialytic interval. The more these changes approach a physiological condition (i.e. changes are small and gradual) the better the cognitive functioning may be.
We choose to wait consistently for 24 h after a dialysis session to avoid effects of post-dialysis desequilibrium (‘dialysis hangover’) and to test patients when they had more or less comparable uraemic solute concentrations.
In our opinion, this is the fairest way to compare the two dialysis modalities. Testing immediately after dialysis or just before the next session (creating a 48-h interval with CHD with higher uraemic solute concentrations) could have yielded larger differences in outcome between SDHD and CHD [20], but we felt this not appropriate when comparing SDHD and CHD as modalities per se.
Third, the issue whether the second control period should have been scheduled after 6 months has been discussed earlier.
Last, for unclear reasons, 73% of the 56 home haemodialysis patients, who were asked to participate in this study, were male. Our in-centre group of patients, who are not able or not willing to be treated at home, consists of about 60% males. Therefore, results may not be generalizable to the common dialysis population. To what extent the predominance of males has affected the outcome of the study is again a matter of speculation. Gender may affect QoL, but this does not implicate that women will respond to SDHD differently from men, and thus, that the inclusion of a larger percentage of female patients would have affected the outcome of our study, even when far more patients were included.
In conclusion, SDHD improves general and disease-related health, as perceived by the patients, but not self-perceived social and mental dimensions of QoL. It has no clear effect on the alpha peak frequency in qEEG and does not change cognitive functioning. Resumption of CHD after cessation of SDHD leads to a significant decrease in QoL and EEG alpha peak frequency but, again, not to a change in cognitive functioning.
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Acknowledgments |
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This study was supported by a grant from the Dutch Kidney Foundation.
Conflict of interest statement. None declared.
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Accepted in revised form: 12. 4.06
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