Background
Survival of hemodialysis patients is strongly related to the type of vascular access. Numerous studies have shown that arteriovenous (AV) access (either fistulae or grafts) is associated with lower mortality [
1‐
4] and fewer morbid events [
5,
6] than central venous catheters. Guidelines for vascular access agree that AV access is the best option for hemodialysis patients, but there is no consensus about the optimal timing for creation, especially for AV fistulae [
7‐
9]. Hence, AV access use at hemodialysis initiation does not come close to meeting current therapeutic goals [
10]. Only 18% of US patients start hemodialysis with functional AV access, and this rate does not exceed 30 to 45% in Europe [
2,
3,
11,
12].
The lack of functionality of a significant number of AV fistulae and grafts created before hemodialysis initiation results in initial catheter use. Nonfunctionality rates of about 18% are reported among the overall populations of incident hemodialysis patients in Canada and the US [
2‐
4]. Rates as high as 45% have been observed in elderly patients with predialysis AV fistula creation [
13]. Because of differences in patient selection and practices for AV access placement [
14‐
16], nonfunctionality rates, their determinants, and outcomes may differ between Europe and North America. Only a few studies have investigated outcomes when AV access was nonfunctional at hemodialysis initiation, all of them in North America [
2,
3,
13]. They report that survival is poorer with a nonfunctional than functional AV access and worst with catheters alone [
2,
3]. High rates of vascular access conversion in patients starting dialysis with a nonfunctional AV access may explain their better outcome, as suggested by studies in patients who started with a catheter and subsequently converted to a functional AV access [
17‐
19]. Nonetheless, considering outcomes specifically after hemodialysis initiation with nonfunctional AV access is important in the context of the current
Fistula First Catheter Last initiative, which seeks to increase the use of AV fistulae in patients in whom they are deemed feasible [
20]. We therefore used data from the French Renal Epidemiology and Information Network (REIN) registry to study changes of vascular access in patients starting hemodialysis with a nonfunctional AV access and the impact on outcome in a setting with relatively high AV access use.
Discussion
This study shows that in France, where the rate of predialysis AV access placement is relatively high, nonfunctional AV access at hemodialysis initiation is common and does not appear to have decreased over time. A substantial percentage of patients with nonfunctional AV access at first hemodialysis may never acquire a functional AV access which is associated with increased mortality risk. In contrast, the outcome of patients with a nonfunctional AV access converting to a functional one appears similar to that of those starting with a functional AV access. These findings have important implications for clinical practice and public health policies.
The 9% frequency of nonfunctional AV access at hemodialysis initiation in our study is of the same order of magnitude as that reported in Canada (9%) [
4], but lower than in the US (18%) [
2,
3]. Nevertheless, the relative weight of nonfunctional AV accesses among all those created predialysis was much lower in France than in North America. About 16% of patients with predialysis AV access started hemodialysis with a catheter in France, while this percentage was 33% in Canada and about 50% in the US. The Dialysis Outcomes and Practice Patterns Study (DOPPS) has pointed out several differences in both patient characteristics and clinical practices between Europe and North America that may explain this discrepancy. For instance, hemodialysis patients in North America have more comorbidities than those in Europe [
26], and these are well established determinants of poor AV access use and patency [
27,
28]. Most striking, however, are the differences in practices. Not only are rates of AV access at hemodialysis initiation in Europe substantially higher than in North America [
14,
29], but surgical training has been shown to differ between these 2 regions, and more training with AV access, as found in Europe, is associated with both AV access creation and patency [
30]. Once an AV access is placed, the involvement of the access surgeon in monitoring it for maturation and functional use or in planning for another access in case of failure may impact functionality rates. Nevertheless, information is lacking about the relationship of the access surgeon to the dialysis patient after AV access is placed. Earlier AV fistula cannulation in European countries [
14] may also partly explain the lower prevalence of nonfunctional AV access in our study.
As expected, nonfunctional AV access at hemodialysis initiation was associated with an increase of 10% in overall mortality risk, compared with functional AV access. Since AV fistulae account for 97% of the AV access in France, this increased risk is lower than the 30% excess mortality associated with maturing compared with mature AV fistulae observed in all US adult patients who started dialysis between 2006 and 2010 [
3]. This excess mortality risk was even higher in elderly patients in the US [
2]. Discrepancies in mortality risk estimates associated with nonfunctional AV access at hemodialysis initiation between the 2 countries may, however, reflect differences in the rate of conversion to functional AV access after dialysis initiation, as our findings suggest. The availability of updated vascular access status during follow-up in the REIN registry enabled us to determine that patients with nonfunctional AV access at hemodialysis initiation had lower rates of functional AV access during the first 3 years of RRT than patients who started with functional AV access, but higher rates than patients who started with catheter alone. Our results indicate that the excess mortality risk in patients starting hemodialysis with a catheter, either because no AV access was placed or because it was nonfunctional, is limited to patients who remained on dialysis with a catheter. Thus, once a permanent vascular access was in place for patients with nonfunctional AV access at initiation, their mortality risk was similar to those with functional AV access at first dialysis. Nevertheless, despite adjusting for several potential confounders, we cannot completely rule out a selection effect, with healthier individuals chosen for AV access conversion, as an explanation of the better outcome of this subgroup of patients. Such a selection effect is at least partly indicated by the overall poorer health condition of patients who did not convert to a functional AV access, notably in the catheter only group. Moreover, patients with a catheter alone at baseline and subsequent functional AV access had the lower mortality risk among the studied groups.
These findings, however, are consistent with those from DOPPS, which showed that in patients initiating dialysis with a catheter, conversion to a permanent AV access was associated with an adjusted mortality HR of 0.69 (95% CI, 0.55–0.85) [
18]. Similarly, the HEMO study showed no difference in mortality risk between patients with long-term AV access versus those who converted from catheter in the preceding year of treatment [
17]. Likewise, in prevalent dialysis patients treated in Fresenius Medical Care facilities, catheter conversion to AV access within a 4-month period was associated with a mortality risk in the following 8 months similar to that of patients with AV access from the outset of the follow-up [
19].
Our finding that survival was similar in patients with functional AV access after hemodialysis initiation, regardless of their vascular access at the start, should not be interpreted as calling into question the fistula first principle. In our study, only 63% of patients with nonfunctional AV access at initiation converted to a functional one. Moreover, the catheter use itself may have prevented conversion to a functional access for some patients: catheter use is associated with mortality risk, and some patients may have had catheter-related early deaths. Moreover, catheter use may contribute to subsequent AV access failure due to central venous stenosis [
5,
31,
32]. Given that AV fistulae may never be successful for some fraction of patients because of their poor vascular condition, the potential of AV grafts for reducing catheter use should be considered. Studies in the US have shown similar outcomes for AV fistulae and AV grafts in some subpopulations [
33,
34].
Major strengths of this study include the size and unselected nature of our registry-based population, which enable generalization of our results to France and other European countries having similar context. In addition, we were able to take major potential confounders into account in the multivariate analyses, including numerous comorbidities and treatment conditions. Lastly, updated information on vascular access was available, and very few patients were lost to follow-up.
Our study also has limitations. First, the prevalence of nonfunctional AV access may be underestimated due to missing AV creation dates. Because the presence of AV access itself at start is not recorded, but only its date of creation if any, we do not know how many patients among those with no reported creation date had no AV access and how many had a missing date for AV access creation. The percentage of missing dates is known, however, for patients who started with functional AV access (15%). Simulation of missing date rates showed that their potential impact on the prevalence estimate of nonfunctional AV access would be low: for example, 10% instead of 9%, if the missing date rate was 15% for both the functional and nonfunctional AV access groups, and 13%, if this rate was twice as high (30%) for the nonfunctional access group. Second, available data did not allow to specify whether the nonfunctional access was patent but not sufficiently matured, or failed and not salvageable. Finally, the vascular access update was interval-censored, which may have resulted in misclassification. Nevertheless, sensitivity analysis using the end of each interval provided consistent findings. Moreover, because annual updates in the REIN registry concern patients’ permanent treatment, our data are likely to reflect outcomes associated with long-term use of a given vascular access.
Acknowledgements
We thank all the registry participants, especially the nephrologists and professionals who collected the data and conducted the quality control. The dialysis units participating in the registry are listed in its annual report:
http://www.agence-biomedecine.fr/IMG/pdf/rapport_rein2013.pdf. Part of this work was presented orally at the 53rd congress ERA-EDTA in Vienna, Austria, May 21st–24th.