The timely construction of arteriovenous fistulae: a key to reducing morbidity and mortality and to improving cost management

Teresa Ortega1,2, Francisco Ortega1,2, Carmen Diaz-Corte1, Pablo Rebollo1,2, Jose Ma Baltar1 and Jaime Alvarez-Grande1

1 Hospital Universitario Central de Asturias, Health Outcomes Research Unit, Nephrology Service, Oviedo, Asturias, Spain and 2 Institute Reina Sofia, Oviedo, Asturias, Spain

Correspondence and offprint requests to: Teresa Ortega, Hospital Universitario Central de Asturias, Health Outcomes Research Unit, Nephrology Service, Oviedo, Asturias, Spain. E-mail: tortega{at}hca.es



   Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background. Some investigators have shown that the initial placement of a catheter or graft, instead of the timely construction of an arteriovenous fistula (AVF), late referral to nephrology services and unplanned dialysis increase morbidity and mortality in chronic haemodialysis (CHD) patients. Furthermore, a delay in providing an adequate AVF entails significant increases in treatment-related costs. This study was limited to the analysis of the effects of the lack of an adequate vascular access for CHD on morbidity and mortality.

Methods. According to the vascular access they had in the first 3 months of CHD treatment 96 patients were divided into three groups (VA group): Group 1 (G1), having an adequate AVF in the first 3 months; Group 2 (G2), starting with a catheter but finishing with an AVF; and Group 3 (G3) starting and finishing with a catheter. Time-dependent Cox regression analysis was performed to identify variables associated with survival, and the standardized mortality index (SMI) was calculated. Finally, we studied cost-effectiveness.

Results. Time-dependent Cox regression and logistic regression analyses showed the statistically significant variable to be the VA group. To ensure that mortality was comparable between VA groups, eliminating age bias, the findings were adjusted applying SMI. G1 patients appear to have a lesser risk of death (relative risk, 0.39) than G2 and G3 patients, as do G2 relative to G3 patients. Also, after adjustment with SMI, patients over 65 years, presumably at greater risk of death, have a lower mortality than the ≤65 age group. Patients with an adequate and functioning AVF lived longer than the others, and the cost of each ‘death prevented’ was lower ({euro}3318/patient).

Conclusions. The lack of an adequate AVF at the start of haemodialysis decreases survival significantly—even if patients are not diabetic, are referred to a nephrologist early and planned haemodialysis is initiated. It also increases the cost of each prevented death.

Keywords: arteriovenous fistula; cost-effectiveness; chronic haemodialysis; morbidity; mortality



   Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Numerous studies in patients with end-stage renal disease (ESRD) have indicated that the impact on the morbidity and mortality of these patients that is caused by the timing of the initiation of chronic haemodialysis (CHD) is variable, depending on whether or not the initiation of CHD was planned following the nephrological consultation [1,2]. Gallego et al. [3] found that incident patients who initiated unplanned dialysis had a risk of death 1.72 times greater than those whose dialysis was planned by a nephrologist; and patients without an autologous arteriovenous fistula (AVF) at the start of CHD had 1.75 times greater chance of dying than those with. Pastan et al. [4] showed for the first time that prevalent patients who had dialysis through catheters had a greater mortality than those who were dialysed via an AVF. So, one of the variables that most influences morbidity and mortality is the type of vascular access patients have when starting CHD: AVF, catheter or graft. Delay in having an AVF for haemodialysis implies the prolonged use of external vascular access (catheters), which may cause many problems—infections, sepsis, etc. [5]. Its results are frequent and extended hospital admissions and a reduction of the quality of life and survival of patients initiating CHD, and increases in costs [6]. Several factors, then, influence morbidity and mortality in CHD patients: early or late referral to a nephrologist and to outpatient services provided in a hospital medical centre [1–3,7], diabetes mellitus (DM) as a main diagnosis and the timing of the execution of an AVF, catheter or graft at the beginning of, or after the intiation of CHD.

In Spain, however, AVFs account for 80% of vascular access in prevalent patients on CHD and for 50% of incident patients, as they do in other European countries [1,8].

The National Kidney Foundation's Dialysis Outcome Quality Initiative (DOQI) recommends that from its very beginning CHD should be via an AVF (instead of catheters), since it gives better results, requires fewer corrective interventions, and therefore entails lower morbidity and costs [9–11]. However, the increasing age of patients complicates the application of that recommendation [12].

The aim of the study was to determine, the influence on patient morbidity and mortality and cost of care of different types of vascular accesses used at the inception of CHD—excluding other possible confounding factors, such as late referral to a nephrologist, unplanned dialysis or DM.



   Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Patients
All patients over 18 years who started CHD between 1 January 1996 and 31 December 2000 at the Nephrology Service in Hospital Central de Asturias were included (n = 164). Data were collected on patients through 31 December 2002, their last follow-up visit, or their death, whichever occurred first. The criterion for entering CHD was a creatinine clearance lower than 10 ml/min/1.73 m2 (<15 in those patients whose main diagnosis was DM). Of the 164 patients (Figure 1), 31 were excluded: those who started CHD after losing a renal graft, those who recovered sufficient renal function to be able to leave dialysis and those who were lost to follow-up in the first 3 months of dialysis as a result of either moving to centres outside the region or death. Patients with late referral to the nephrologist (≤1 month before their first dialysis) or to outpatient services provided in a hospital medical centre (n = 24) were also excluded in the analysis of the data, because dialysis had been urgently performed due to renal insufficiency. Also excluded were patients with DM as their main diagnosis (n = 13). The 1 month cut-off for late referrals was established, because if a patient had been referred more than a month before a first haemodialysis, he or she could have had an AVF in a week, and in 2 or 3 weeks it would have matured. This cut-off has been established previously by other investigators [13,14].



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Fig. 1. Division of the patients in the final cohort: the vascular access (VA) groups according to the access options used in the first 3 months.

 
Study method
The remaining 96 patients constitute the study cohort. They were divided into three groups (VA group) according to the vascular access they had during their first 3 months of CHD: Group 1 (G1), having an adequate AVF throughout the first 3 months; Group 2 (G2), starting with a catheter but finishing with an AVF in the first 3 months; and Group 3 (G3), starting and finishing with a catheter during the first 3 months (because their AVF failed or did not function effectively).

The data we collected for each patient included demographic characteristics, comorbid conditions (measured by the number of coexistent pathologies, according to Evans’ index [15,16]) and history of vascular access—the latter with regards to the the following: (i) modality (AVF according to anatomical location—wrist, elbow, etc.; the material of an artificial graft—gore-tex handle, for example; or catheter and mean cost); (ii) time in days between the decision to make the AVF and its effective functioning (puncture and sufficient flow) and time from nephrologist's decision to make an AVF to the start of haemodialysis (in days); (iii) length of time a catheter is in place until an adequate AVF; (iv) de novo morbidity and mortality during the wait for an adequate AVF (infection episodes due to an external temporary catheter, episodes of bacteriaemia, bacteriaemias with haemodynamic repercussions, hospital admissions and stays and their cause(s), subsequent direct or indirect deaths, types of external catheters and their mean cost).

We also calculated a standardized mortality index (SMI) and did a cost-effectiveness analysis [17,18], as will be discussed below.

Data analysis
Some values are presented as mean (±SD) and others as a total number (percentage). Some of the variables of the study were re-codified, such as age ≤65 and >65 years), comorbidity (three groups according to the number of pathologies: 0, 1–2 and ≥3) and de novo morbidity (in two groups: those without problems, and those with infections and mortality attributable to the vascular access). Baseline characteristics between the vascular access options (VA groups) were compared using the chi-square test, the Student t-test and ANOVA, along with Scheffe's test.

Survival was assessed by calculating Kaplan–Meier survival curves, and the groups were compared using the log-rank test. To determine any association between a priori patient characteristics (age, sex, comorbidity and VA group), and patient survival, we used time-dependent Cox regression analysis, in which VA group is related to the time to having a functioning AVF during the 3 months following the beginning of CHD. Other factors, a posteriori (morbidity and hospital admissions), were considered as confounding factors in relation to VA group patient survival. The effects of a posteriori variables (a consequence of the process) was then examined by entering them into separate models of logistic regression that included the a priori significant variables.

On the other hand, to compare the ratios of mortality between the established vascular access groups we calculated the SMI. Though it was calculated by decades, the result appears only in two age ranges: ≤65 years and >65 years, for each AVF group. This index was calculated using mortality rates in Spain in 2000 by age group and the formula SMI = observed deaths/(annual mortality rate x years of monitoring).

Finally, we studied cost-effectiveness, comparing VA groups. An economic evaluation could be realized from different points of view: society, the hospital, the government, etc. This study was made from a hospital perspective and analytical accounting was used. We chose to ignore several costs (pharmaceutical cost, transport, amortization, maintenance, external services, etc.), taking into account only those described below which were calculated as direct and indirect costs. The direct ones were fixed, because all patients finally had an AVF, whether successfully functional or not. Therefore, the creation of an AVF was included in cost accounting: the cost of surgical procedure and personnel, mean hospital stay attributable to the vascular access procedure, and prior medical consultation. The indirect costs were quantified: (i) catheter implantation results: (a) the average number of catheters actually used for each patient and their mean cost, (b) the average of half hospital stays (equivalent to a few hours of admission, the time needed to place a catheter) and cost, (c) the average of catheter placement by a nephrologist and its cost; (ii) complications arising from catheter infection: (a) the mean length of a hospital stay and (b) the cost of each hospitalization. Effectiveness was measured by the percentage of deaths prevented in relation to the number of patients in each VA group. Cost-effectiveness was calculated as a ratio between the total cost of a VA group and the number of the patients in it at the starting point, minus the number of deaths attributable to the choice and timing of access in that group.



   Results
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 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The clinical records of 96 patients were checked; in all of them the initiation of CHD was planned in advance. Table 1 shows the characteristics of the patients divided according to their vascular accesses and the results of univariate analyses (VA group as study variable). The data show that in more than half of the patients CHD was begun via an adequate AVF (G1). The mean age of G1 is statistically significantly lower than of the other two groups. There are more men in G1 and G3, but more women than men in G2. With respect to comorbidities, 40% in G1 had no associated problems, while a similar percentage of patients had three or more associated problems in G2 and G3. On the other hand, with respect to morbidity, 2% of patients in G1 had infections, 29% in G2 and 38% in G3; and two deaths occurred, one in G2 (4%) and one in G3 (5%). Of G1 patients, 16% were hospitalized, vs 33% in G2 and 62% in G3. A total of 88 external catheters (91% uncuffed) were used in 50 patients (1.76 catheters/patient) with a mean implantation cost of {euro}861/catheter (mean cost of catheter plus cost of one-half hospital stay plus cost of a catheter insertion by a nephrologist = 210 + 161 + 490 = 861).


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Table 1. Descriptive statistics and results according to vascular access (VA) group and results

 
In the Kaplan–Meier analysis, there were a number of statistically significant differences between the three VA groups, G1 having greater survival (P<0.01), with respect to age (P<0.01), sex (P<0.01), comorbidity (P<0.01) and a posteriori variables (P<0.01). Time-dependent Cox regression was then applied (Table 2) to identify variables that had independent associations with survival. It was carried out in steps including the statistically significant a priori variables. This model showed that age, comorbidity and the VA group had independent associations with survival (P<0.05).


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Table 2. Time-dependent Cox regression analysis with the a priori variables

 
A logistic regression was then applied for a posteriori variables (Table 3): (i) the de novo morbidity as the dependent variable and (ii) hospital admissions; and applied as covariables were age, sex, comorbidity index and VA group. Only the VA group was a statistically significant variable (P<0.01) in both cases (Table 3).


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Table 3. Logistic regression: the effect of a priori variables on morbidity and admissions: (a) de novo morbidity as the dependent variablea and (b) hospital admissions as the dependent variableb

 
SMI according to age was applied to each VA group (Table 4). The result indicates that the longer the time before an adequate AVF, the greater the risk of death, i.e. patients in G1 had a lower risk of death than patients in G2 and G3, as did those in G2 vs G3, as determined by using time-dependent Cox regressions (Table 2). Also, among patients older than 65 years (SMI in G1, G2 and G3 = 4, 7 and 5, respectively), who presumably would have greater risks of death, the relative risk is lower than in patients ≤65 years (SMI in G1, G2 and G3 equal to 3, 18 and 20, respectively) after adjustment for SMI.


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Table 4. The SMI for 96 patients compared with the general population

 
According to our cost-effectiveness analysis, the following benefits, measured by cost and death(s) prevented, were obtained {euro}3318/death prevented in G1, {euro}7982/death prevented in G2 and {euro}9471/death prevented in G3 (Table 5).


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Table 5. Effectiveness and cost-effectiveness analysis

 

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Table 6. Mean cost per patient ({euro})

 
Therefore, the cost-benefit obtained, considering only the differences of costs between the VA groups, would have been {euro}4331 with respect to G2 (difference between the {euro}7649 that the care of each G2 patient costs and the {euro}3318 cost of a G1 patient) or {euro}5702 with respect to G3 (the difference between the {euro}9020 cost of each G3 patient and the {euro}3318 cost of a G1 patient) (Table 6). The total net profit would have been {euro}223 686 if all patients had had an adequate AVF timely (difference between actual cost, {euro}542 214 and the cost if all had been in G1, 96 patients x {euro}3318 = 318 528).



   Discussion
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 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
The aim of this study was to determine whether or not the timing of an AVF in relation to the initiation of CHD affected morbidity, e.g. due to infections related to catheters and other complications, and if it influenced patient survival. In the survival analysis, subsequent deaths were associated with the VA grouping, but also with age and comorbidity. Probably, there are other hidden factors in the VA groupings, such as vascular disease, blood flow rates, duration of ESRD, etc., that might in part explain the increased risk of mortality among patients dialysed through catheters. Nevertheless, haemodialysis with a venous catheter increased the risk of death from all causes, not just infection-related mortality [4]. Our results indicate, however, that there exists a relationship between the timely creation of an adequate AVF and morbidity and mortality (Table 1): a greater number of hospital admissions and a longer stay being associated with the use of catheters, which entail complications and translate into increases of costs.

In this study, 47% of patients started CHD without AVF. Although this is similar to the situation in the rest of Europe, it could be improved. This problem depends less on nephrology services than on the planning within the surgical services responsible for the implementation of AVF. The emergent arrival of patients and problems in the scheduling of surgery or the construction of adequate functional fistulae are reasons why some AVFs were not generated in a timely fashion, although patients were being followed by the Nephrology Service as preterminal patients. Nevertheless, the timely construction of the AVF in patients who enter CHD is a prime objective if morbidity and mortality and costs are to be improved.

On the other hand, the problem of not having an adequate AVF at the beginning of CHD is probably accentuated by the age and comorbidities of the patients starting on CHD. This results in greater difficulties in vascular surgery not counteracted by increased care and surgical determination. It is possible that higher haematocrits could reduce the efficacy of an AVF [19].

Furthermore, it is suggested that the higher morbidity and mortality among G2 and G3 patients is related to their greater age compared with G1. In the multivariate analyses, morbidity (Table 2) and mortality (Table 3) were related to the delay in obtaining an adequate AVF (the only statistically significant variable), but it is possible that age influenced the apparent results, especially with respect to mortality. Therefore, to verify if the delay in having an adequate AVF was the principal risk factor in mortality (Table 4), we used SMI to compare the mortality of our patients with that of a ‘normal’ population of the same age. The really significant finding, however, is that among G1 patients the relative risk of death is almost the same for those ≤65 years and >65 years, while in G2 and G3 the relative risk of death is greater in the younger patients rather than in the older. This finding is similar to that reported in the literature [20]. Therefore, it is necessary not only to make an effort to reduce the morbidity and mortality of those patients in whom an adequate AVF is not constructed in a timely fashion, but also to pay special attention to the younger patients, whose relative risk of death is greater than of the older ones.

Several limitations of our study should be noted. First, we did not consider problems such as ‘insufficient’ dialysis dose, bad nutrition, inflammatory state, refractory anaemia with increasing doses of human recombinant eritropoyetin, etc. They have effects that are closely associated with a ‘bad dialysis’ due to not having an adequate AVF at the beginning of the ESRD. Secondly, the analyses of the data of a retrospective study can only reduce bias for those recorded covariables that were recorded in the clinical history (covariables that would be documented in a prospective study). Therefore, some unknown variable or variables could possibly affect the study results. Thirdly, the number of subjects in each of our three groups is small, and the confidence intervals around the risk ratios in the Cox and logistic regression analyses are large, meaning that precision is low.

Although the cost-effectiveness analysis interpreted data on actual costs, it can be used to make more rational decisions with regard to the economic use and allocation of health resources. The result of this analysis shows that those patients who entered CHD with an adequate AVF, G1, had a lower estimated cost for their care than the rest—a saving of 41% compared with G2 and G3 (Table 6). Since most patients might have had CHD initiated with a functioning AVF, the additional expense arising from the use of ‘unnecessary’ catheters is taken into account in this study and is considered as increasing the cost. The use of most of those catheters might have been avoided, but weaknesses in resource management increased the cost of care.

In short, bearing in mind that the age and comorbidities of a patient influence morbidity and mortality as well as costs, having an adequate AVF at the beginning of a programmed CHD might have reduced the percentage of patients who had infections and other complications (sepsis, thrombosis, haematomas, etc.) and might have obviated two theoretically attributable deaths. Given its crucial role in patient outcome, the planning and management of vascular access by the medical team should be improved.



   Acknowledgments
 
This work was supported by a grant (Exp. No. 01/10056) from Fondo de Investigaciones Sanitarias, Proyecto de Evaluación de Tecnologías Sanitarias, Ministerio de Sanidad.

Conflict of interest statement. None exists.



   References
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 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

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Received for publication: 26. 3.04
Accepted in revised form: 24. 9.04