Chair of Nephrology, University of Turin, Italy
Correspondence and offprint requests to: Giorgina B. Piccoli, Cattedra di Nephrologia, Departmente di Medicina Interna Corso Doguom 16-10126 Torino Email:gbpiccoli{at}hotmail.com, giorgina.piccoli{at}unito.it
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Abstract |
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Methods. All patients were treated in a limited care and home haemodialysis unit with a stable caregiver team (November 1998November 2002). Vascular access failure, surgical treatment, angioplasty and declotting were studied alone or in combination by univariate and multivariate models. We analysed the effects of age, sex, comorbidity, previous vascular events, schedule, setting of treatment (home, limited care), dialysis follow-up, vascular access (native vs prosthetic, first vs subsequent) and setting of vascular access creation. Intention to treat and per protocol analyses were performed.
Results. In 2160 patient-months (home dialysis: DHD 400 months, non-DHD 655 months; limited care: DHD 208 months; non-DHD 897 months), 57 adverse events occurred (27 failures), in which 30 were at home (nine DHD) and 27 were in limited care (five DHD). The probability of remaining free from adverse events at 6 and 12 months was 89% and 80% on DHD and 79% and 76% on other schedules (intention to treat). Univariate analyses revealed a significant difference for the setting of the vascular access creation (lower risk of vascular access complications in our centre) and sex (male sex was protective). Logistic regression and Cox analyses confirmed the role for the setting of the vascular access creation.
Conclusions. Although DHD did not appear as a risk factor for vascular access morbidity or failure at home or in a limited care centre setting, the setting of vascular access creation may influence its success.
Keywords: daily haemodialysis; home haemodialysis; self-care dialysis; vascular access
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Introduction |
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One of the most feared clinical problems with DHD is the risk of vascular access failure, caused by frequent needle punctures. This has been a concern for DHD since the inception of this method [9]. Despite claims to the contrary, there are limited data examining the risk of vascular access failure and these mainly tested home haemodialysis. However, the latter represent a biased selection, since home haemodialysis patients are usually young and without comorbidity and they are often examined over long periods of time or in different centres, thereby introducing additional potential bias of heterogeneity [1012]. Furthermore, a detailed search strategy (Appendix 1) revealed that the focus was on vascular access failure in the few papers examining DHD and vascular access failure. Less is known about related morbidity, which is an interesting problem given that vascular access failure can be prevented by careful surveillance and timely interventions. Therefore, in strictly controlled settings, analyses focused on vascular access failure may underestimate the incidence of other morbidities [13,14].
The aim of the present study was to test the hypothesis that vascular access survival is equivalent in the DHD schedule and in non-daily treatment in a cohort of DHD patients treated at home or in a limited care centre by the same caregiver team over the same period of time in a single centre (November 1998November 2002; Chair of Nephrology, University of Turin, Italy). A prospective historical study design was chosen to test the hypothesis.
Because of the main potential confounding factors pointed out in the literature, we not only compared daily dialysis with conventional schedules, but also examined the treatment setting and the caregiver team, the treatment history, the presence of mainly vascular comorbidities and the vascular access history. To account for the potential bias of underestimating the treatment risks caused in cases of careful surveillance and timely preventive measures (surgical revision, angioplasty), we evaluated a classical endpoint consisting of vascular access failure and a composite endpoint composed of all the interventions involved in vascular access.
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Subjects and methods |
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The caregiver team consisted of one nephrologist, two trainee nephrologists and a growing nursing team (four nurses in November 1998 and 10 in November 2002).
Selection for DHD
A DHD trial was proposed to all of the patients, but was offered first to home dialysis patients (for logistical reasons) and then to patients in the limited care centre where a short DHD shift was added to the previous two sessions (www.multi-med.com/homehemo) [15,16]. Patients from other units or other centres were also accepted if there were no contraindications for out-of-hospital dialysis.
Clinical data at baseline
The data collection reflected the usual work-up of haemodialysis patients in our setting. No additional controls were scheduled to avoid patient discomfort. Patients were aware that their (anonymous) data were to be employed for research purposes.
Comorbidity was defined by the nephrologist caregiver (G.B.P.) according to the usual clinical criteria. Diffuse vascular disease was diagnosed by severe, diffuse calcifications in X-rays and/or from clinical events (amputation, stroke). Cardiac disease was diagnosed by a cardiologist according to the usual clinical and echographic parameters. Hypotension was defined as usual pre-dialysis systolic blood pressure (SBP) measurements <100 mmHg, while hypertension was defined as several pre-dialysis SBP measurements 140 mmHg and/or diastolic BP
90 mmHg.
Dialysis schedule
Dialysis schedules were individually tailored: blood flow 250350 ml/min; dialysate flow 500 ml/min; needles 1516 gauge; weight loss 0.71.2 kg/h; membranes of polysulphone, polyamide or excebrane; and surface 1.72 m2. Daily dialysis was designated as five to six sessions per week (23 h). Duration of conventional dialysis ranged from 3.30 to 4.45 h (www.multi-med.com/homehemo) [17,18].
Vascular access surveillance
Vascular accesses were assessed at each clinical visit (on each session by the nurses in the dialysis unit and by the nephrologist on the occasions of the periodic controls for home dialysis patients and for patients on dialysis in the unit) and upon demand (all cases with suspected vascular access malfunction or macroscopic modifications of the vascular access). Detection of vascular access dysfunction was based on physical examination (inspection and palpation for pulse and thrill at the arterial, mid and venous sections of the access), monitoring of venous pressure during dialysis, measurement of access recirculation, monitoring of unexplained decreases or increases in the measured amount of haemodialysis delivered, physical findings of persistent swelling of the arm, clotting of the graft and prolonged bleeding after needle withdrawal.
All accesses were tested for recirculation every 6 months (glucose dilution technique) [13]. An ultrasound scan of the vascular access was performed annually or on demand, according to the previous criteria. Antiplatelet and dicumarolic agents were used in selected cases, upon advice from the vascular access surgeon (nephrologist of the same team). At the last update, 14/42 patients in the home haemodialysis cohort were on antiplatelet agents (13 cases) or on dicumarolic agents (one case) (given for cardiac or vascular reasons in 13/14) and 17/35 patients in the limited self-care unit cohort were on antiplatelet agents and one was on dicumarolic agents (14/18 for cardiac or vascular reasons) (chi-square test, P = 0.272). The prevalence of these drugs was not different between DHD (13/28 patients on antiplatelet, none on dicumarolic agents) and non-DHD (17/49 on antiplatelet, 2/49 on dicumarolic agents) patients (chi-square test, P = 0.377).
For the prevention of infections, the home haemodialysis patients and partners were informed about standard infection control measures [13].
Type of outcomes
Only patients with vascular accesses other than central catheters were considered. If a patient was switched to a central venous catheter after the failure of an arteriovenous fistula, he/she was considered as lost to follow-up at that date. Patients who received a renal graft or who changed referral dialysis centres for logistical reasons were considered as lost to follow-up after that date. To avoid a selection bias, vascular access events occurring within 6 months after the switch to hospital dialysis for clinical reasons were also recorded (three patients were switched to hospital haemodialysis for clinical reasons, but no event recorded). These follow-ups were added to the total count.
The measured endpoints included, first, vascular access failure (defined as need for a new vascular access in the absence of sufficient blood flow to allow performing haemodialysis; the lack of response to mechanical declotting or urokinase in case of acute failure; and lack of response to pre-emptive surgical treatment or angioplasty in case of subacute problems) and, second, all events in combination (need for surgical treatment, angioplasty, declotting with urokinase). The decisions for pre-emptive interventions (surgical revisions or angioplasty) were taken on clinical grounds and made whenever possible by the surgeons who had performed the vascular access together with the nephrologist caregiver. There were no specific thresholds for the haemodynamic tests. The team approach included the opinion of the angioradiologist when angioplasty was a possibility.
The decision for mechanical declotting or declotting with urokinase was also taken on clinical grounds and was based on the presence of residual flow (palpatorial or at echodoppler), the time from the vascular access closure (urokinase was preferred in the case of problems occurring within 24 h) and the type of problem (urokinase was preferred in the case of venous problems, whereas it was given limited use during arterial malfunction).
The same criteria were used for home haemodialysis patients and for patients treated in the unit.
Data analysis
The data analysis, performed with SPSS version 11.5, consisted of three steps that included descriptive, univariate and multivariate analyses.
Power analysis
The power analysis was performed using Epi Info 2002 software (www.epiinfo.it). Assuming a power of 0.80 and an error of 0.05, with an exposed/unexposed ratio of 1:1.5, the sample of recruited patients was able to detect a relative risk of two or higher in a univariate analysis while comparing DHD patients with patients on other schedules.
Descriptive analysis
Continuous demographic [age at renal replacement therapy (RRT) start, age at study onset] and clinical (duration of follow-up) variables were described using the median and range as descriptive statistics for non-parametric data. Dichotomous data (sex, comorbidities, type of vascular access) were expressed using prevalence as the descriptive statistic.
Gross incidence was calculated as the number of events per 100 patient-months.
Univariate analysis
The parameters considered independent variables were age at study (dichotomized at the median), sex, years of RRT before the beginning of the study (dichotomized at the median), previous vascular problems (yes/no), diabetes and/or vascular comorbidity (yes/no), dialysis schedule (DHD, other), setting of treatment (home, centre), setting of vascular access creation (our unit, other units) and type of vascular access (native vs prosthetic, first vs subsequent).
Differences between means were tested using chi-square tests (Pearson or Fisher tests) and MannWhitney tests, as appropriate.
The dialysis setting was assessed according to an intention to treat analysis, that is, patients in training for home haemodialysis were placed in the home dialysis cohort.
The dialysis schedule (daily vs other schedules) was assessed according to intention to treat and per protocol analyses.
The probability of remaining free from adverse events was assessed by the KaplanMeier method. The outcomes were divided into first adverse event (any type) and first vascular access failure. Differences among KaplanMeier curves were calculated by the log-rank test.
Logistic regression
The variables included in the univariate analysis were used as covariates in the logistic regression model. Two dependent variables were tested: freedom from vascular access failure or freedom from any adverse event.
Cox model
The time-dependent Cox proportional hazard model was used to investigate the risk of the first adverse event and the risk of access failure. Since only two independent variables were significant in the univariate analysis (in the per protocol analysis: sex and setting of vascular access creation), two approaches were chosen: inclusion in the model of only the significant variables or inclusion of all the variables of specific clinical interest (sex, previous access events, home vs in-centre dialysis, daily vs non-daily dialysis, years of RRT).
The dialysis schedule (daily vs other schedules) was assessed according to intention to treat and per protocol analyses.
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Results |
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Despite the young age, comorbidity (mainly cardiovascular) was common and was probably due to our policy of broad indications for home or out-of-hospital haemodialysis (Table 1).
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The vascular access types are summarized in Table 1. Here, the prevalence of native vascular accesses was >70% in all the subsets.
As expected from the lower dialysis follow-up and from the lower age, the prevalence of first vascular access was higher on home dialysis (71.4%) than on limited care dialysis (60%).
The most common vascular access on all schedules was the native radio-cephalic fistula.
Upper arm fistulas, prosthetic devices and central venous catheters were less common and were chosen mainly in patients with long RRT follow-up or multiple comorbidities (Table 1). The seven patients who had vascular access performed elsewhere were not different from the other cases in age (median: 57.5 years; range: 30.664.9 years vs median: 48.2 years; range: 21.878.5 years; P = 0.160), sex (P = 0.403), RRT follow-up pre-study (median: 15.6 months; range: 0.0377.3 months vs median: 13.1 months; range: 0.0279.9 months; P = 0.481), type of vascular access (100% native, none prosthetic vs 79% native, 21% prosthetic, P = 0.333; first in 57% of cases vs 65%, subsequent in 43% of cases vs 35%, P = 0.694) or prevalence of comorbidity (present in 43% vs 35%; P = 1.0). In total, 100 vascular accesses were observed throughout the period and of these 93 were created by our team of nephrologists and seven were created elsewhere in patients subsequently referred to our unit (three treated at home, one on DHD; four in-centre, two on DHD).
Vascular access failure and adverse events
During the 2160 patient-months of follow-up, 27 vascular access failures and 30 other vascular events (need for pre-emptive surgical treatment, angioplasty or declotting) were recorded in 29 patients (15 on home haemodialysis and 14 on limited care dialysis) (Tables 2 and 3). The gross incidence of events was 2.6/100 patient-months.
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This lack of significant difference (according to treatment setting or schedule) was confirmed by the vascular access failure rate: gross incidence was 1.2 failures per 100 patient-months (at home: 1.5/100 patient-months; limited care: 1.01/100 patient-months; DHD: 1.3/100 patient-months; non-DHD: 1.2/100 patient-months).
Multivariate analysis
Logistic regression
Four logistic regression models were tested that alternatively used vascular access failure/all events as dependent variables and two sets of covariates. The first one included sex, previous vascular events, comorbidity, DHD, home haemodialysis, setting of vascular access creation, prosthetic arteriovenous fistula; the second one added age and years of RRT to the previous. The only significant model was that which took into account the smaller set of covariates (sex, previous vascular events, comorbidity, schedule, setting of treatment, setting of vascular access creation and prosthetic vs native vascular access) and vascular access failure as the dependent variable (likelihood test of the model: P = 0.046). The only significant covariate was the setting of vascular access creation, in which access creation in our unit was a protective factor in preventing vascular access failure (relative risk: 0.028; significance of the covariate: P = 0.001).
Although the analysis was repeated with an intention to treat design, none of the tested models reached significance.
KaplanMeier analysis
The probability of remaining free from adverse events at different time intervals is reported in Table 4. The different numbers in the per protocol analysis are due to the separate counts of each treatment period.
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There were no adverse event differences between dialysis schedules (probability of remaining free from adverse events at 6 and 12 months: on DHD, 89% and 79%; on dialysis schedules other than DHD, 80% and 76%). Likewise, the treatment setting did not affect the outcome, as shown in Figures 1 and 2.
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In the per protocol analysis, the first step model was not significant for all events but was significant for vascular access failure (P = 0.001); the only significant element was the setting of treatment (relative risk: 0.051, corresponding to a protective effect of our centre; P = 0.001). When the analysis was limited to sex and setting of vascular access creation, the model was significant for all events (P = 0.040) and for failures (P = 0.000), but the setting of treatment was significant only in the analysis examining the endpoint of vascular access failure.
In the intention to treat analysis, the model was significant only for failures (P = 0.005) and the importance of the setting was confirmed (P = 0.001). The second step was not performed because of the lack of significant data in the intention to treat analysis (only the setting).
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Discussion |
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Although there is no evidence for disadvantages of DHD, fears of vascular access failure or related morbidity have been higher when DHD was offered as a rescue treatment for patients with multiple comorbidities and low dialysis tolerance, as in our setting (Table 1).
Despite claims of favourable effects of DHD on vascular access survival, there are only a few reports on this subject coming from a limited number of centres in Europe and North America [1012,2022].
Analyses of vascular access survival and morbidity are plagued by several methodological problems and biases. For example, there is an important country effect in that vascular accesses are prepared by nephrologists in Italy and to some extent in France, while in North America this task is mainly carried out by vascular surgeons. In addition, a centre effect involves the presence of an experienced surgeon-nephrologist, surveillance policies and dialysis schedules. Furthermore, the selection for DHD is variable, since in some settings it is mainly a home dialysis treatment for a positively selected population [10], while in others it may also be a rescue treatment for a negatively selected subset of dialysis patients [5].
We have offered single trials of daily dialysis to patients wanting to experience this treatment option [15] and we accepted elderly patients and patients with multiple comorbidities (at home or on limited care). Because of this, only 23.8% of home haemodialysis patients and 17.1% of limited care patients in the present study were free of comorbidity (Table 1). There was no specific selection made by the caregivers on the basis of vascular access type. However, the low prevalence of prosthetic accesses (16.6% on home haemodialysis, 20% on self-care dialysis) testified to the skill of the surgeon nephrologists who performed the vascular accesses (Table 1).
The major focus of this study was to compare DHD results in home and limited care settings, wherein both were followed by the same small, homogeneous caregiver team throughout the study. In the 2160 patient-months analysed, there were 57 adverse events that were almost evenly divided between failures (27 cases) and other events (30 cases), as well as between home (30 events) and limited care (27 events). The analyses took into account different models and combinations of covariates. They were performed both per protocol, while assessing the frequent treatment changes in the setting of a multiple choice dialysis network, and as intention to treat, to provide a more robust analysis revealing the long-term effects of a treatment.
In this cohort having a high prevalence of comorbidity, the probability of remaining free from adverse events was relatively high: 89% at 6 months and 80% at 12 months on DHD and 79% at 6 months and 76% at 12 months on other schedules (analysed as intention to treat).
The univariate or multivariate analyses failed to detect differences in the risk of vascular access failure or morbidity between the DHD and non-DHD populations as well as between home dialysis and limited care.
Interestingly, most of the tested models were not significant (logistic regression and survival analysis), suggesting that factors other than the wide set of covariates tested (sex, duration of RRT, type of vascular access, setting of its creation, etc.) were important for access failure.
Only sex (a protective role of males was found in some univariate and multivariate models) and setting of vascular access creation were significant in the logistic regression when we employed a smaller set of covariates with vascular access failure as the outcome in the per protocol analysis. In the Cox model, only the setting of vascular access creation was significantly correlated with the probability of remaining free from adverse events in all the combinations tested (per protocol and as intention to treat, with different sets of covariates).
While the disproportion in vascular accesses between our centre (93 cases) and elsewhere (seven cases: three on home dialysis, four in-centre, three on DHD) will require further study with longer follow-ups, the data clearly underline the importance of a skilled nephrosurgical team.
As with other DHD studies, ours was limited by small sample size, which was caused by the limited application of this treatment modality. Overall, our data were able to detect a relative risk of two or more when comparing daily vs non-daily treatments. This limited sensitivity creates the possibility that lesser differences might have gone undetected. Selection bias might represent an alternative explanation. For example, and in contrast with the literature, our population was negatively selected and comorbidity might have masked the DHD effect. On the other hand, the funnel plot distribution of small case series might explain the presence of discrepant data, at least until more evidence is gained in larger populations [23,24].
Although our population was relatively homogeneous, it was different from the overall dialysis population in our area, making the present data of limited use in other settings. While our analysis attempted to account for potential confounders identified at the start of the study, the low number of cases did not allow for clear conclusions, especially when smaller subsets were considered.
The compromise to dichotomize the data and to simplify the treatment or vascular access histories (for example, the data for histories were expressed as first and subsequent vascular accesses without taking into account the number of previous accesses that may have provided good markers of risk of failure) might have resulted in a lack of clear threshold effects at different levels.
Furthermore, despite similar baseline conditions in the daily and non-daily dialysis subsets, certain biases might have been present, such as the younger daily dialysis cohort, which presumably put them at lower risk for adverse vascular events than the non-daily population. The daily cohort also had a longer RRT follow-up, which presumably put them at higher risk of adverse events. The choice of daily dialysis was up to the patients and their compliance and disease understanding was, therefore, probably better, which reduced the risks. Finally, the dialysis tolerance of longer sessions was presumably lower, providing good reason for choosing daily dialysis, and this might be a marker of overall increased vascular comorbidity.
At present, there is probably no analytical method to account for these methodological problems and biases. Only further development of daily dialysis programmes will provide adequate data to overcome the presently unavoidable heterogeneity biases and will take into account the limited and sparse experiences from around the world [3,5,1012,21].
With these limitations in mind, our data may be useful for generating new hypotheses for future analyses. It will be particularly interesting to examine the centre effect found in the present study, which was limited by the low number of cases and by the uneven distribution of the two subsets.
In conclusion, in settings where careful vascular access surveillance was performed, DHD did not emerge as a significant risk factor for vascular access morbidity or for vascular access failure.
Since the statistical power of our study was limited, with a relative risk detection of only two or more, further studies will be necessary to detect smaller but potentially clinically relevant differences and to allow comparisons to other haemodialysis categories, such as hospital haemodialysis, and to other centres with different approaches to vascular access creation and management.
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Appendix 1: MEDLINE (1966 to late October 2003) |
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MeSH = Medical Subject Headings
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Acknowledgments |
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Conflict of interest statement. None declared.
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References |
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