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NDT Advance Access published online on April 3, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn010
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Clinical effectiveness and quality of life of conventional haemodialysis versus short daily haemodialysis: a systematic review*

Jeannete Puñal1, Leonor Varela Lema1, Domingo Sanhez-Guisande2 and Alberto Ruano-Ravina1,3,4

1 Galician Department of Health, Galician Agency for Health Technology Assessment, Santiago de Compostela 2 Nephrology Service, Clinic University Hospital of Santiago de Compostela 3 Department of Preventive Medicine and Public Health, University of Santiago de Compostela 4 CIBER de epidemiología y salud pública, CIBERESP, Spain

Correspondence and offprint requests to: Alberto Ruano Raviña, Galician Department of Health, Galician Agency for Health Technology Assessment, Edif Administrativo de San Lázaro, San Lázaro s/n, 15781 Santiago de Compostela, Spain. Tel: +34-981-541831; Fax: +34-981-542854; E-mail: alberto.ruano.ravina{at}sergas.es, mralbert{at}usc.es



   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Background. End-stage renal disease is a troublesome health problem worldwide. The most usual renal replacement therapy is conventional haemodialysis (CHD), performed three times a week, 3.5–4 h per session. It has been proposed that this schedule is unphysiologic and that daily haemodialysis would be a more appropriate schedule. One of the variants of daily haemodialysis is the so-called short daily haemodialysis (SDHD), performed five to seven times per week, 1.5–3 h per session. The objective of this paper is to compare, through a systematic review, the clinical effectiveness and safety of SDHD versus CHD.

Methods. The following databases were searched: MEDLINE, EMBASE, NHS Centre for Reviews and Dissemination (HTA, DARE and NHS EED), Cochrane, ISI Web of Knowledge, IME and IBECS. Two independent reviewers decided which papers were to be included after applying inclusion and exclusion criteria. Any discrepancy was resolved by consensus. The quality of the included papers was measured using a quality scale developed for the purpose of this report.

Results. Seventeen original articles were included. There were no randomized controlled trials. SDHD seems to be more effective than conventional dialysis. Patients on daily haemodialysis seem to present less vascular access problems, better control of hypertension and in turn a reduction in the antihypertensive treatment, better quality of life, lower incidence of ventricular hypertrophy, lower consumption of rHuEPO due to the better control of anaemia and a reduction in the use of phosphate binders as a consequence of the better control of plasmatic phosphorous.

Conclusions. SDHD might result in a better clinical effectiveness, mainly through a better control of the arterial tension and, therefore, a lower consumption of antihypertensive drugs, and a better quality of life than CHD.

Keywords: end-stage renal disease; daily haemodialysis; MeSH terms: renal replacement therapy; renal dialysis; systematic review



   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
During the last decade, chronic kidney disease (CKD) dependent on renal replacement therapy (RRT) has increased in all countries, and despite the technological advances, there have been no significant improvements in survival [1]. Currently, it is thought that an occult renal disease exists in a relatively high percentage of the population, as has been detected by the EPIRCE study in Spain [2]. This fact could also be present in other developed countries. At a world level, the highest incidence rates of end-stage renal disease (ESRD) are observed in the USA, Taiwan, Qatar and Japan. In the USA, 336 patients per million population (pmp) initiated RRT in 2003, whilst in European countries, in no case did this figure exceed 200 pmp. Survival of incident patients undergoing dialysis at 1, 2 and 5 years of follow-up is 85.7%, 75% and 49.4%, respectively [1].

In most countries, haemodialysis (HD) is the therapy of choice for patients with CKD [3]. Maintenance haemodialysis, using diffusion through hollow fibre cuprophan membranes can be dated back to the 1960s [4]. Since then, different HD modalities have emerged. A recent review has updated the published evidence on their effectiveness [5,6]. There is also variability in the HD frequency. While the conventional schedule is three times per week, it has been suggested that a more physiological dialysis would be a daily schedule, with six times per week during 1.5–3 h, usually called short daily haemodialysis (SDHD). There are other HD frequencies, such as long nocturnal HD, where HD is performed 8 h each night or the Tassin experience, three times per week and a duration of 8 h per session [7].

The objective of the present paper is to compare the clinical effectiveness and the quality of life of SDHD with conventional haemodialysis (CHD) through a systematic review of the literature.



   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Literature search
A systematic search of the literature was performed. The databases used were MEDLINE (Pubmed), EMBASE (Silver Platter), CRD (NHS Centre for Reviews and Dissemination), DARE (Database of Abstracts of Reviews of Effectiveness), NHS EED (Economic Evaluation Database), Cochrane Library Plus, ISI Web of Knowledge (Institute for Scientific Information, Philadelphia), as well as other national databases. Search strategies were created for each database using different combinations and variations of the following core search strategies: (‘hemodialysis’ or ‘haemodialysis’ or ‘dialysis’) and (‘daily’ or ‘quotidian’ or ‘frequent’ or ‘home’). The search also included other databases that provided information on ongoing clinical trials and research projects such as ClinicalTrials.gov, Centerwatch and HSRPROJ (Health Services Research Projects in Progress). A fully recursive search of reference lists of relevant papers was performed to find studies not identified by the previous search. The search was restricted to studies published in English, Spanish, French, Italian or Portuguese, between January 1995 and January 2007.

Paper selection
Papers identified in the search were reviewed separately by two of the authors and those considered potentially relevant were selected for further analysis. The full text of these papers was obtained and the two reviewers independently checked each trial for fulfilment of selection criteria (Table 1). The relevant data were rigorously extracted and recorded in evidence tables that included information on study type, inclusion/exclusion criteria, patient characteristics (age, sex, comorbidities and time on dialysis) and follow-up data.


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  		Table 1 Selection criteria of the studies included in the review

 
The papers were classified depending on the type of outcome variables evaluated: vascular accesses complications, cardiovascular outcomes, anaemia and EPO dosage, nutritional status, therapy efficiency, morbidity and quality of life.

Study quality assessment
Study quality was assessed using a specific scale adapted from a previous study on haemodialysis [6,8]. The included papers were assessed in a blinded way by two independent reviewers. Differences >5% in the use of the scale were not allowed and discrepancies were resolved by consensus after reviewing again carefully the study assessed. The concordance was measured using the intraclass correlation coefficient which is equivalent to the kappa index for continuous variables [9,10].



   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Search results
The search strategy used identified 1.673 references. Of these, 69 studies were considered to be potentially relevant and were read at full text. After applying the inclusion/exclusion criteria, 17 articles were included in the systematic review [11–27] (Figure 1). The majority of studies were carried out in the USA and Italy. Only two studies were published before the year 2000, one in 1996 [12] and the other in 1999 [16]. The details of the included studies may be observed in Table 2.


Figure 1
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  		Fig. 1 Identification and selection of studies.

 

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  		Table 2 Studies comparing daily haemodialysis (HD) versus conventional dialysis (CD) included in the systematic review

 
Effectiveness of short daily haemodialysis
Vascular access problems.
Seven articles [11,18,20–24] assessed the incidence of vascular access-related complications. Of these, two [22,24] showed that patients receiving daily dialysis had a lower incidence of vascular access occlusions and a higher vascular access survival in relation to patients on conventional HD. Ting et al. [21] observed an average of 0.94 problems/year on DHD versus 1.01 on conventional HD, but this difference was not statistically significant. Martins Castro et al. [18] showed an elevated vascular accesses survival and a low number of failures on SDHD, not reporting outcomes on conventional HD. The other three studies found similar incidences of vascular access failure with both HD frequencies [11,20,23].

Cardiovascular outcomes: hypertension control and left ventricular hypertrophy.
Six of the eleven trials that assessed the effect of short daily versus conventional dialysis on blood pressure control observed greater reductions in both systolic and diastolic aortic blood pressures for patients on daily dialysis [11,12,16,19,22,24]. Williams et al. [23] observed a decrease in the systolic blood pressure during SDHD only. One paper [14] showed five hypertensive patients during conventional HD that turned normotensive on SDHD. In three studies, the decrease in blood pressure during daily HD was not significant [15,21,26].

In 13 papers a comparison was made of medication requirements during daily and conventional dialysis. Several studies found that when patients were transferred from conventional to short daily dialysis they could discontinue or reduce the doses of antihypertensive drugs [12,14,19,21,23,24] or required a lower association of different antihypertensive drugs [21,22]. The results of these studies are summarized in Table 3.


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  		Table 3 Blood pressure and antihypertensive drug requirements reported in the included studies

 
Five studies observed a significant reduction in cardiac hypertrophy parameters when patients were changed from conventional to daily HD [12,14,16,24,26]. Other investigations found similar values for both dialysis regimens [11,15]. In a study carried out by Odar-Cederlöf et al. [17], elevated predialysis levels of B-type natriuretic peptide decreased when patients were transferred to daily dialysis. Floridi et al. [13] showed that an SDHD regimen could lower the mean levels of glycation-related substances observed in CHD.

Anaemia and EPO dosage.
The majority of trials observed that erythropoietin doses could be reduced during the SDHD period [14,15,19,21,24,26] even though some studies reported no significant changes [11,22]. In the study carried out by Ting et al. [21] EPO requirements were reduced in 45% after 12 months of follow-up. Traeger et al. [24] also observed a significant reduction after 1 year but EPO requirements increased slightly with longer follow-up periods (up to 6 years). During the daily HD period, the EPO treatment could be discontinued in some patients [14,19]. For example, Koshikawa et al. [19] found that in 14 patients treated with SDHD, EPO was retired in 2 and doses reduced in 5 patients.

Nutritional status.
Ten studies reported the effects that daily dialysis had on various nutritional parameters. Significant improvements were observed in the majority of the nutritional parameters studied [protein intake, normalized protein nitrogen appearance rate (nPNA), calorie intake, fluid intake, mean dry weight, body mass index and lean body mass] when patients were transferred from CHD to SDHD [14,16,21–24,26]. Body weight gain increased in some studies [14,19,21] but decreased [24,26–28] or remained unchanged in others [16].

Therapy efficiency.
With the exception of one study [27], all articles showed that the daily dialysis dose (Kt/V) was increased in the short dialysis period [11,19–21,23,24,28]. Williams et al. [23] found that with daily dialysis, phosphorous removal per week increased by 10%. Five out of seven studies that provided results on serum phosphate levels found that these were reduced during SDHD [23–26,28]. Reynolds et al. [11] found no significant change for this parameter. Another trial [27] observed that the predialysis serum phosphate concentrations decreased until 6 months of follow-up on SDHD and remained similar at 12 months of follow-up compared to 6 months.

Whilst some studies showed a reduction in phosphate binder usage when patients were switched to daily haemodialysis [14,26,28], others found no significant modifications [11,21,27]. Only one [24] of the three [11,22,24] studies that assessed β2-microglobulin levels during SDHD found statistical significant differences between CHD (30.5 ± 11 mg/dl) and SDHD (24.6 ± 7.8 mg/dl).

Morbidity.
The results of three studies that compared hospitalization rates and length of stays during the SDHD and CHD period showed opposite results. Whilst one study found a decrease in the number of admissions and length of hospital stays during the SDHD therapy [21] another study found an increase in these events [23]. In one investigation no significant differences were found between the two dialysis modalities [11].

Quality of life.
Quality of life assessments were carried out using different questionnaires, such as Kidney Disease Quality of Life-Short Form (KDQOL-SF) [19,21,22], SF-36 [11,24] and Alberta Quality of Life Instrument [23]. Practically all of the studies observed that the overall assessment of quality of life improved when patients were on SDHD therapy [11,14,19,21–24]. Significant improvements were reported in various symptoms (cramps, chills, hypertensive episodes, itchy skin and lack of appetite), energy status, burden of kidney disease, social interaction, physical functioning and mental health status [21–23]. In general, patients reported that they were feeling better during the daily dialysis period [21–23]. The results on quality of life are shown in Table 4.


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  		Table 4 Quality of life results observed in the included studies

 
Assessment of the quality of the included studies
The average scores awarded by the two independent investigators for all the studies included in the review are presented in Figure 2. The average maximum score achieved was 71% [26] and the average minimum score 34.5% [12]. The overall quality was low since the mean and median scores were <50% (48.94% and 45%, respectively). Concordance between the two independent investigators was high. The intraclass correlation coefficient was 0.96 (IC 95%, 0.89–0.98), demonstrating a high level of agreement between the two reviewers.


Figure 2
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  		Fig. 2 Mean quality score of the included papers.

 


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
The results of this systematic review suggest that SDHD might offer a better clinical effectiveness than CHD in terms of hypertension control and medication requirements, including EPO treatment. There does not seem to be any differences in vascular access related complications. A better clearance of AGE peptides, urea and phosphate has also been observed. All the studies included are consistent with a better quality of life for patients treated with SDHD versus conventional HD.

It has been previously suggested that the risk of vascular accesses failure and the incidence of complications such as stenosis could be greater in SDHD due to the frequent needle punctures. Despite these claims previous studies did not relate the frequency of punctures with vascular accesses dysfunction [29,30]. Some studies have shown that other risk factors such as advanced atherosclerosis, altered haemostasis and metabolic abnormalities (diabetes, hyperlipidaemia etc.) could be predictors of fistula dysfunction [31–33]. The results of this review suggest that there are no significant differences in vascular problems between CHD and a short daily dialysis. Some investigations have even reported that fistulas have better outcomes with daily haemodialysis compared to chronic haemodialysis [34–36]. Some of the reasons that may explain this finding would be a better blood pressure control [37], improved haemostasis [38] with decreased haematoma formation at the puncture level [39] or reduced homocysteine levels [40].

The improvement in blood pressure control and the reduction in antihypertensive treatment has been previously explained by a reduction of extracellular fluid excess [35,41,42]; these outcomes were also observed in two included papers [15,22], a better control of dry weight that would help attain a lower interdialytic volume [11,14] and a better control of sodium balance [12,19]. With short daily dialysis the volume status is more stable over time than with CHD. In the studies reviewing these factors were clearly correlated with a reduction in antihypertensive medications when patients achieved better blood pressure control [11,12,14,19,23,24]. When there were no blood pressure improvements or these were very slight, changes in these parameters did not lead to lower medication consumption [15,22].

Another finding in relation to medication consumption was the reduction in phosphate binder usage in patients who received short daily dialysis. Since these treatments are indicated for the control of phosphorous levels, it is indicative that SDHD provides a higher clearance of these products and reduces serum phosphorus levels. Hyperphosphataemia can induce vascular calcification [43] and probably contribute to left ventricular hypertrophy [44], thus suggesting an important mechanism for the possible beneficial effects of SDHD.

The reduction of erythropoietin treatment observed in many studies [14,15,19,21,22,24,26] could reflect not only a better nutritional status but also the greatest removal of uraemic toxins that may play a role in inhibition of erythropoiesis and therefore contribute to the improvement of anaemia and to the lowering of erythropoietin doses [34,45,46]. Nevertheless, some investigations have shown a higher need for EPO drugs and this could be associated with higher blood losses [22] or increased phlebotomy or inflammation due to the more frequent dialysis sessions and consequent exposure to the extracorporeal circuit that can enhance inflammation [11].

The results are not clear as to the improvements in hospital admissions rates or length of stays. Hospitalization rates are directly associated with the number and severity of the comorbidities and also with the safety of the dialysis technique. Some studies suggest that SDHD causes less interdialytic fluid fluctuations and gives more freedom to the patients to elaborate their diet and this is likely to bring about a better appetite and hence a better nutritional status [24,34,47–49] with the disappearance of anorexia [14], a condition very frequent in haemodialysed patients. The improvement in nutritional status, hormonal levels and other improvements associated with the greatest removal of substances related to uraemia should result in a better well-being, less complications and, as a consequence, fewer and shorter hospital admissions [16,50]. This effect was not reflected in all of the studies analysed in this paper. Whilst the hospitalization days and rates decreased in two studies [18,21], they increased [23] or remained unchanged in other investigations [11]. This is noteworthy, since if it is expected for SDHD to have better clinical results this fact should be reflected in hospital admissions, which is not the case in the revised literature. SDHD seems to contribute to a higher clearance of advanced glycation end-products (AGEs) [13]. AGE peptides derived from the catabolism of glycated proteins accumulate in the plasma of patients undergoing HD and may contribute to the onset of some long-term complications such as atherosclerosis, amyloidosis and neurodigestive processes [51–55]. Reductions in left ventricular hypertrophy parameters, possibly due to better blood pressure control [12,24], decrease in interdialytic weight gain [24,26] and decrease in predialysis plasma levels of natriuretic peptide [17], were other findings observed and these are of clinical interest because they are well-known risk factors for cardiovascular disease. The left ventricular hypertrophy cardiovascular disease is the leading cause of death in patients with ESRD [56].

In comparison to CHD, short daily dialysis presented a greater urea clearance (Kt/Vurea) [11,19–21,23,24,28]. It has been previously suggested that urea clearance can fluctuate during the dialysis session, with the dialyzer urea clearance higher in the first hours of the session and lower at the end [57]. The shorter duration of the dialysis sessions in SDHD could explain the increased urea clearance.

There were no significant reductions observed in the removal of β2-microglobulin and this could be due to the high molecular weight of this protein, 11 800 dalton [34,58]. It has been shown that SDHD is more efficient than CHD in the clearance of low and intermediate molecules but does not provide a higher removal of high weight molecules, such as β2-microglobulin [34].

Whilst the majority of studies show a greater clearance of phosphorous in short daily dialysis [23–26,28], others do not find significant changes [11,27]. Buoncristiani et al. [59] have pointed out that SDHD sessions >2 h do not lead to an increased removal of uraemic substances, suggesting that 2 h is the ideal scheme and differences in the session duration cannot explain the observed discrepancies. It has been indicated that clearance of phosphorous can depend on the predialysis levels of phosphorous, this clearance being higher when these levels are >5 mg/dl [60–63]. Ayus et al. [64] have suggested that SDHD is not very efficient when serum phosphorous levels are between 4 and 4.5 mg/dl.

The studies reflected that the quality of life improved when patients were transferred from conventional dialysis to SDHD [11,14,19,21–24]. Similar results have also been observed in the London Study (Ontario, Canada), where patients reported a better quality of life in both SDHD and nocturnal haemodialysis when compared with CHD [65,66]. The studies included in the present review reported reductions in the incidence of symptoms such as nausea, vomiting, itchy skin, cramps, chills, hypertensive episodes and dizziness during daily dialysis treatment, which reflects a better dialysis tolerance. Improvements were also reported in physical and mental health status. Results were consistent even though different questionnaires and instruments were used to measure quality of life, some specific to renal disease and others to general health survey questionnaires such as SF-36. Although results suggest that quality of life is improved for SDHD versus CHD, it cannot be ruled out that this improvement could be simply due to the change to a new procedure, since in these cases there is frequently an increase in the attention paid to a patient. Furthermore, researchers involved in studies assessing the effectiveness of a new therapy tend to be enthusiastic about on its results and there exists the possibility of transmitting this enthusiasm to the patients included, influencing the results. It is important to note that two studies that have not been included in this review because they did not comply with the inclusion/ exclusion criteria, have found that some patients were not willing to change from a CHD to an SDHD schedule [67,68]. These two studies found that 44% [67] and 59% of the patients [68] were reticent to start short daily dialysis for various reasons, such as a greater dependence on a dialysis machine and a worsening in their quality of life regarding social relationships, and this aspect must be taken into account when deciding to implement a SDHD schedule.

There are certain limitations in this systematic review. Since there is no MeSH term for haemodialysis nor for the different dialysis modalities, it complicates the search query in the PubMed (Medline) database. We had to use a search strategy with free text words to find the bibliography so we cannot exclude having missed some articles, even though we feel this is highly improbable since we hand-searched references lists of all articles retrieved and found no additional articles.

This systematic review did not consider all daily dialysis treatment schedules, but considered only those frequently defined as short daily dialysis schedules: five to seven times per week sessions with lengths ranging from 1.5 to 3 h. The findings of this review cannot, therefore, be generalized to other daily schedules such as long nocturnal haemodialysis or schedules with much longer durations. Two studies [36,69] were excluded from the present analysis because daily dialysis was performed at home in the majority of patients (70% and 80% were treated at home, respectively). The decision to exclude these studies was taken after consulting with various nephrologists, since it was considered that these patients could present a better compliance with the dialysis schedule, better haemodynamic profiles and less comorbidities.

The different prescribed dialysis doses among studies, and even within the same study, greatly limit the drawing up of conclusions. When comparing both haemodialysis frequencies, the ideal situation would be one where the dialysis doses were the same for both. Nevertheless, in some of the assessed studies Ting et al. [21] and Ayus et al. [26], the weekly time on dialysis was longer in SDHD than in CHD (13–18 h versus 12 h) while in others [12,27] the CHD weekly time was fixed at 12 h and the SDHD was highly variable (9–22 h/week). Four of the included papers [11,16,20,25] did not show the total duration of dialysis sessions at least in one of the frequencies assessed. These differences in the Kt/V achieved could affect the overall results, the clearance of phosphorus and also the patient's quality of life. Our report strongly supports the need for better quality studies to assess the effectiveness of SDHD.

Another important shortcoming is the low overall mean and medium quality scores achieved by the studies, which were <50%. Concordance between the two independent reviewers was high, indicating that the scale specifically designed for this review was easy to use and can clearly differentiate low- from high-quality studies. The most important shortcomings found were small sample size, short follow-up periods and restrictive inclusion/exclusion criteria that do not allow for a generalization of the results to all of the dialyzed population.

It has to be kept in mind that in the present systematic review there are some decisive aspects that are not discussed because they were not the objective of this work. These aspects would be related to daily haemodialysis such as transportation to the facility (entailing higher costs), higher perceived burden of disease and higher consumption of consumables. A higher dropout of patients in the SDHD arms of the included studies cannot, therefore, be dismissed, perhaps overestimating the positive results.

In conclusion, the literature analysis indicates that in general terms, clinical outcomes might be better with short daily dialysis than with CHD. The main findings were improvements in blood pressure control and medication requirements. There were no differences found regarding morbidity or mortality and this is noteworthy since it is the ultimate expected result of SDHD versus CHD. The evidence supports the hypothesis that quality of life improves when patients are transferred from a conventional to a SDHD regimen although neither of the quality of life studies surpassed 50 patients. The randomized clinical studies that are currently underway will provide good quality and valuable information to determine the real effectiveness of daily dialysis in comparison to CHD.



   Acknowledgments
 
The authors wish to thank Dr Maduell from the Hospital Clinic of Barcelona for the critical review of an extended version of this manuscript. This study was funded by the Health Research Fund (Fondo de Investigaciones Sanitarias–FIS) grant PI05/90003 from the Spanish Ministry of Health & Consumer Affairs as part of a research project entitled ‘Clinical effectiveness of two frequencies of chronic hemodialysis: conventional versus short daily hemodialysis.’

Conflict of interest statement. None



   Notes
 
* The full systematic review (110 pages) can be downloaded in Spanish completely free through the webpage of the Galician Agency for Health Technology Assessment (http://avalia-t.sergas.es/). Back



   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Received for publication: 5. 9.07
Accepted in revised form: 7. 1.08


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R. Pellicano, B. J. Strauss, K. R. Polkinghorne, and P. G. Kerr
Body composition in home haemodialysis versus conventional haemodialysis: a cross-sectional, matched, comparative study
Nephrol. Dial. Transplant., September 17, 2009; (2009) gfp490v1.
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