Zero upper arm hemodialysis fistulas: utopian or realistic goal?

Introduction

International guidelines support the use of distal native fistula as the best first-line vascular access (VA).^{1 –3} Radio-cephalic fistula at the wrist is commonly accepted as a VA which guarantees fewer complications (stenosis, overflow syndrome, thrombosis, and distal ischemia).^{1 –5} Another essential advantage of the distal fistula is saving more proximal sites of the forearm for creating future VA, such as the midarm fistula ⁶ or fistula with the proximal radial artery. ⁷ Despite these indications, the number of upper arm fistulas (UAFs) constantly increases worldwide, except in Japan. ⁸ Time trend analyses of arteriovenous fistula (AVF) location from DOPPS phases 1 to 5 (1996–2015) indicated that lower-arm AVF use has declined in Europe/Australia-New Zealand from 77% in DOPPS phases 1 to ~65% in DOPPS phases 5. ⁸ Previous survey in our Department, including about 50% of Hemodialysis patients (HPs), showed a prevalence of UAF of less than 5%. ⁹ This data contrasts the findings reported in our country by the DOPPS 5 study ⁸ and the Italian national survey conducted in 2022 on over 15,000 HPs, ¹⁰ which showed a UAF prevalence of 33% and 30%, respectively. The significant difference in the prevalence of UAF between our Department and the Italian dialysis population has attracted our attention. Could these data be reliable? Could erroneous patient recruitment have generated unrealistic results? We selected all Hemodialysis patients from our Department to investigate VA prevalence and remove this bias. This study aims to determine the type and location of vascular access and clinical variables associated with VA placement in 100% of our Department’s prevalent HPs.

Methods

We conducted a multicenter survey in all hemodialysis facilities throughout the southern department of Puglia. It includes 1,400,000 people, with 1365 patients on dialysis (1295 on hemodialysis and 70 on peritoneal dialysis). The patients came from 12 public no-profit hospitals, 4 for-profit facilities, and one catholic hospital. The department uses a Hub and Spoke model for VA management. The hub performs simple and complex AVFs including Graft placement, the Percutaneous Transluminal Angioplasty (PTA) of fistulas and central stenosis, and the surgical and endovascular rescue of thrombosed or stenotic fistulas. Nephrologists perform most of the surgical and endovascular interventions alone. Interventional radiologists handle central vein stenosis, while vascular surgeons are involved in cases requiring the removal of a large aneurysm or complex surgery. The spokes are four and primarily perform simple distal AVFs (Figure 1). We investigated the VA prevalence of all 1295 HPs in December 2021. For this aim, in February 2022, an Excel survey was distributed to each dialysis unit to collect data; the recruitment of patients ended in May 2022, when all patients were included in the research. Demographic data on age, dialysis vintage, gender, and comorbidities were collected. The comorbid conditions taken into account were heart disease (arrhythmia, coronary artery disease, or heart failure), obesity, advanced cancer, diabetes, previous kidney transplant failure, and peripheral vascular diseases. In addition to demographic data, we recorded the initial type of vascular access: central venous catheter (CVC), which distinguished between cuffed or non-cuffed, and native arteriovenous fistula (AVFs) or prosthetic fistulas (Graft).

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Figure 1.

Hub and Spoke model for the management of Vascular Access in the southern Nephrology and Dialysis Department of Apulia (Italy).

We classified the AVFs according to location into lower arm fistulas (LAF), including both distal forearm fistula (DFF) and middle proximal forearm fistula (MPFF), and upper arm fistula (UAF). The number of previously created AVFs was registered. Assuming a correlation between the prevalence and incidence of vascular access, we examined surgeries performed at the HUB over the last 9 years.

The survey contains closed-ended questions and used Excel for data storage, analysis, and multicenter data sharing. All statistical analyses were performed using a t-test and chi-squared test. According to data distribution, continuous variables have been described as mean with standard deviation [SD] or median and interquartile range [25th; 75th percentiles]. Socio-demographic, clinical, and vascular access type data are presented as percentages. Univariable regression analysis (chi-square test) was used to assess the possible relationship between socio-demographic and clinical variables on the one hand and the type of vascular access (DFF, MPFF, AM, Graft, CVC) on the other hand. Statistical significance was set at the level of p < 0.05.

Participant patients signed an informed consent form that included providing permission to record data anonymously for research and publication purposes.

Results

The survey response rate was 100%. The baseline characteristics of the entire population are shown in Table 1. In the cohort of 1295 chronic HPs, the majority was male (63.6%) with a mean age of 69 ± 12.4 years. The median dialysis vintage for chronic HPs at the end of 2021 was 50 [IQR 22–100] months. The number of patients aged ⩾75 years was 506 (39%), with a predominance of male sex (58.5%); the mean age was 82 ± 4.8 years, and the median dialysis vintage was 46 (IQR 205–97.5) months. The most common comorbidities among chronic dialysis patients were heart disease (21.5%) and type 2 diabetes (20.6%), followed by peripheral arterial disease (13.5%), kidney transplant failure (7.9%), obesity (5.6%), and prior cancer (4.7%). The VA in prevalent HPs was AVF in 938 (76.6%) patients, CVC in 231 (22.5%), and graft in 8 (0.7%) patients. About the location of the AVF, 96.5% were LAFs (84% DFF and 12.5% MPFF), and 3.7% were UAF (Figure 2). At dialysis therapy initiation, 52% of participants were dialyzing with a native AVF and 48% with a catheter (63% with a non-cuffed CVC and 37% with a cuffed CVC). No one starts hemodialysis (HD) with a Graft. Thirteen patients (1%) started dialysis with UAF. Compared to 2013, the 2021 data showed a statistically significant increase in age (p < 0.0001), a decrease in MPFF, UAF, and GRAFT prevalence, and an increase in CVC prevalence (Table 2). In the univariate logistic regression model, patients aged ⩾75 years, women, and subjects with peripheral vascular diseases and diabetes showed a higher prevalence of CVC and a lower prevalence of DFF. Covariates significantly associated with vascular access type at the univariate level are shown in Table 3. Figure 3 shows the types of vascular access by renal Unit. In two facilities, the prevalence of CVC was greater than 40%.

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Table 1.

Demographic and clinical characteristics of the enrolled population.

Enrolled population	1295
Gender	Males 63.62%
Aged >75 years	39%
Mean age (±SD) years	69 ± 12.4
Median dialysis vintage [IQR] months	50 [22–100]
% Comorbidities
Type 2 diabetes	20.62%
Heart disease	21.53%
Peripheral arterial disease	13.50%
Cancer	4.74%
Obesity	5.57%
Prior kidney transplant	7.94%

Quantitative variables are reported as mean with standard deviation [SD] or median and interquartile range [25th; 75th percentiles]; qualitative variables and comorbidities as percentages.

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Figure 2.

Pie chart representation in Vascular Access prevalence in 1295 hemodialysis patients.

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Table 2.

Prevalence of distal forearm fistula (DFF), mean-proximal forearm fistula (MPFF), upper arm fistula (UAF), Graft, and CVC of 1295 patients at December 2021.

	2013	2017	2021	2013 vs 2021
N. patients	737	726	1295
Mean age years	65 ± 14	66 ± 15	69 ± 12.4	p < 0.0001
DFF	63.1%	65%	63.5%	p = 0.86
MPFF	15.2%	14.8%	10.1%	p = 0.004
UAF	4.6%	4%	3%	p = 0.05
Graft	2.3%	1.7%	0.7%	p = 0.003
CVC	14.8%	14.5%	22.5%	p = 0.007

The first columns report data for 2013 and 2017. Data from 2021 compared to 2013 (column on the right side) showed a statistically significant increase in age, a decrease in MPFF, UAF, and GRAFT prevalence, and an increase in CVC prevalence.

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Table 3.

Covariates significantly associated with vascular access type at the univariate level.

	DFF	MPFF	UAF	GRAFT	CVC
Diabetes
Yes	55.8	6.2	1.3	0.9	35.8
No	65.9	10.8	3.5	0.6	19.2
p	0.004	0.05	0.1	0.9	<0.001
Age
⩾75	57.7	9.3	1.6	0.2	31.2
<75	68.3	10.4	4.1	1.0	16.2
p	<0.001	0.5	0.01	0.1	<0.001
Gender
Males	69.3	9.7	3.2	0.5	17.3
Females	55.2	10.4	3	1.0	30.4
p	<0.001	0.7	0.9	0.3	<0.001
Vasculopathy
Yes	40.5	8.8	2.7	1.4	46.6
No	67.2	10.1	3.2	0.6	18.9
p	<0.001	0.7	0.9	0.6	<0.001

DFF: distal forearm fistula; MPFF: mid-proximal forearm fistula; UAF: upper arm fistula; CVC: central venous catheter.

Patients aged ⩾75 years (p < 0.001), women (p < 0.001), with diabetes (p < 0.001), and peripheral vascular diseases (p < 0.001), showed a higher prevalence of CVC than DFF.

The bold text in the table shows data with statistical significance.

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Figure 3.

Types of vascular access by renal unit.

The operative waiting time for the first fistula surgery ranged from 15 to 30 days, 10 days for PTA or surgical revision for stenosis or delayed maturation; the waiting time for surgical or endovascular treatment of thrombotic fistula was generally 24–48 h, with some cases up to 10 days. According to the number of surgical operations, 657 (65%) patients had only one AVF surgery, with 92% of cases being distal AVF; 258 (25%) and 75 (7%), respectively, patients needed a second and third surgery. Only six patients (0.5%) had four or more operations.

Figure 4 reports the type and location of 1350 Vascular Access created in our Unit in the last 9 years.

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Figure 4.

Type and location of 1350 Vascular Access created in the last 9 years in our Unit.

Discussion

The present study provides a comprehensive account of the status of dialysis access care in the South Extended area of Apulia. AVF, CVC, and Graft prevalence in this area were 76.6%, 22.5%, and 0.7% respectively. We found that 48% of patients begin dialysis with a CVC, while the remaining 52% start with a native AVF. No patients use Graft as their primary vascular access; only 13 patients (1%) start dialysis with UAF. The patients starting dialysis with CVC are 622, but prevalent CVC are only 231; it is evident that most patients who initiate dialysis with a CVC subsequently receive a fistula. The prevalence of CVC has significantly increased since our 2013 survey (which includes only 50% of total patients). ⁹ This trend has been observed in various Italian surveys and the report of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) registry.^{11 –14} Many factors can be proposed to explain such growth. Our data, in agreement with precedent studies from Italian and European registries, found a role of female sex, old age, diabetes, and vascular disease in determining CVC prevalence.

Furthermore, late referral to a nephrology team, reported in many countries, could be another possible explanation for the high proportion of catheter use, especially at dialysis initiation.^15,16

In line with global trends, the 2021 data revealed an increase in the average age of our dialytic population compared to the 2013 data. The aging-related oxidative stress and chronic inflammatory processes damage cells and create a stressful environment that promotes the development of cardiovascular diseases. ¹⁷ Although many authors report the technical feasibility of an AVF, ¹⁸ these conditions may limit the use of the Fistula First concept. Nephrologists should individualize the timing and type of vascular access placement based on patient characteristics, preferences, and surgeon experience to achieve optimal outcomes, regardless of age. ¹⁹

Another finding that emerged from our survey was the poor utilization of grafts. In contrast to DOPPS phases 4–5, where arteriovenous grafts accounted for 12%–13% of all created vascular accesses in Europe/ANZ and Japan and for 25% in the US, ⁸ in our study, 0.7% of patients have a graft as permanent vascular access, and no one begins HD with Graft. The limited use of Graft reflects a widespread practice in Italy, as observed in three additional Italian studies where the Graft prevalence was 1%–4%. It is likely due to differing approaches to managing vascular access in other countries, resulting in the development of recommendations that may not be applicable in the Italian context.^10,13,20,21 Wider use of Grafts in our clinical practice could reduce the CVC prevalence.

Despite the increasing prevalence of CVCs, our study has found some interesting data regarding the location of AVFs compared to other studies.^8,10 We found that 96.3% of all AVFs were located in the lower arm, with 84% in the distal forearm and 12.5% in the middle proximal forearm. Only 3.7% were in the upper arm.

This result, which has been stable since 2013, differs significantly from the findings reported in our country by the DOPPS 5 study ⁸ and the 2022 Italian national survey, ¹⁰ which reported 33% and 30% of AVFs in the upper arm, respectively. Our data brings our reality closer to Japan’s results in the DOPPS 5 Study. The low median intradialytic blood flow rate, smaller gauge needles, and proximal vein sparing, combined with an early referral to a nephrologist and an excellent surgical technique, may be significant factors in Japan’s high prevalence of LAFs. ⁸ Based on the clinical characteristics observed in the DOOPS 5 Study, we notice that similar factors influence the location of AVFs in the United States, Europe, ANZ, and our casuistry. Males and younger patients have AVFs located more frequently in the lower arm than females; LAFs were less commonly found in people with diabetes and peripheral vascular disease. Similarly, the disparity in UAF prevalence between our data (3.7%) and the Italian survey (30%) seems unlikely to be attributed to clinical reasons. In our case history, there is a lower prevalence of obesity (5.57%) compared to Italian and regional data, ²² which may explain the decreased proportion of UAF. We cannot directly compare the BMI of our population with the findings of the DOPPS study, which shows that Japan had a lower BMI than the USA and Europe/ANZ. However, the BMI reported by DOPPS for our country has an average of 25.7 kg/m² for the upper and lower fistula, indicating that the percentage of obese people in the Italian population of DOPPS should not be high. ⁸ Thus, other factors may contribute to this significant difference.

In Italy, vascular access management is currently organized at regional and local levels without any shared health policy. Different professionals create arteriovenous fistula and arteriovenous graft across facilities. According to a recent survey in Italy, about 24% of facilities have a Vascular Surgeon performing all VA, 37% of facilities have a Nephrologist serving all VA, and 39% of facilities have a Nephrologist for simple AVF placement and a Vascular Surgeon for complex AVF. ¹⁰ Therefore, several factors influenced the type, location, and timing of vascular access promoted by nephrologists, such as the availability of interventional nephrologists, surgical support, access to interventional radiology, and waiting time for surgical creation or management of fistula complications. Long wait times for surgical creation are a significant barrier to AVF creation. In countries with higher fistula prevalence, such as Italy, Germany, and Japan, wait times from referral to fistula creation ranged from 5 to 6 days. In contrast, in countries with lower fistula prevalence, like the UK and Canada, wait times ranged from 40 to 43 days. ²³ In our department, vascular access management was performed in a HUB and spoke model for many years. This model, in use for over 15 years, was regulated in 2018 by the Apulian Health System with the establishment of the “Apulian Network of Nephrology, Dialysis, and Transplants” (ReNDiT) to organize Dialysis, Kidney Transplant, and Vascular Access activities at regional level. ²⁴ The document identifies three “Extended Areas” (North, Center, and South) and defines the organizational model in “Hub and Spoke.” In the South Extended Area, the spokes perform 40% of the interventions, reducing the HUB’s commitment and the waiting times for the first fistula operations, stenotic fistula recovery operations, and, most importantly, thrombosed fistula recovery operations. It is significant for thrombosed fistulas that require treatment within 24–48 h.

The analysis of surgeries performed at the HUB over the last 9 years (Figure 4) revealed that of 1350 VAs created, only 2% were UAFs and 1.4% were Grafts, while 96% of VAs were LAFs. Indeed, creating a high number of distal fistulas can be a determining factor in the high prevalence of lower arm fistulas.

Knowing why so many LAFs were performed in our unit would be interesting. The skills with some intraoperative procedures could be the cause of these findings. According to Bourquelot and Pirozzi, ⁴ several procedures and precautions, including early referral to the surgeon, precise Preoperative Duplex cartography of vein and arteries, post-operative clinical and Duplex Evaluation of maturation, and percutaneous angioplasty of artery and vein stenosis, have been applied to decrease the incidence of early failure and immature distal fistulas. ⁴

Many intraoperative procedures were introduced in our clinical practice to increase the number of vessels recruited for distal fistulas. Intraoperative Transluminal Angioplasty,^25,26 Intraoperative angiography, ²⁷ Intraoperative Endovascular Lithotripsy,^28,29 and vessel predilatation ³⁰ are commonly used in our unit to recruit patients with insufficient vessels for the creation of distal fistulas. The high prevalence of LAF is likely linked to their high incidence, further supporting the efficacy of these techniques. To support our observations, randomized controlled trials should be required. However, conducting randomized controlled trials in the vascular access field is difficult due to several biases related to differences in patient’s clinical characteristics, different surgical operators, and variations in the healthcare system’s organization and delivery. Furthermore, recreating our organizational model in a different setting could be challenging.

In conclusion, the data confirms the low prevalence of UAF detected in the previous survey involving a subset of HPs. In the South Extended Area, the preference for native AVF as the primary vascular access may explain the lower rate of Graft (only 0.9% in prevalent patients). More efforts should be made to reduce the incidence and prevalence of CVCs, such as raising the incidence of Grafts. Improving predialysis care and reducing late referral patterns can increase the likelihood of a permanent VA at the start of dialysis. However, starting dialysis with a CVC doesn’t limit any switch to the placement of an AVF. The employment of new surgical and intraoperative endovascular techniques, along with pre-operative US mapping, allows for the recruitment of patients with suboptimal vessels for LAF, bypassing the limits of age and vascular disease. The HUB and Spoke model and the availability on-site of interventional nephrologists with expertise in vascular access placement contributed to our findings and their long-term stability.

Zero proximal fistulas is a utopian goal, but it is realistic to reduce the incidence and prevalence of UAF to 5% less, as demonstrated by the Japanese experience.

The challenge is to create a national program for vascular access management, facilitating the sharing of best practices and improving vascular access management across the country while overcoming national differences.