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Clinical Epidemiology
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Long-Term Outcomes of Arteriovenous Fistulas with Unassisted versus Assisted Maturation: A Retrospective National Hemodialysis Cohort Study

Timmy Lee, Joyce Zhang Qian, Yi Zhang, Mae Thamer and Michael Allon
JASN November 2019, 30 (11) 2209-2218; DOI: https://doi.org/10.1681/ASN.2019030318
Timmy Lee
1Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
2Veterans Affairs Medical Center, Birmingham, Alabama; and
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Joyce Zhang Qian
3Medical Technology and Practice Patterns Institute, Bethesda, Maryland
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Yi Zhang
3Medical Technology and Practice Patterns Institute, Bethesda, Maryland
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Mae Thamer
3Medical Technology and Practice Patterns Institute, Bethesda, Maryland
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Michael Allon
1Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
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Significance Statement

Before successful use in dialysis, many arteriovenous fistulas (AVFs) require one or more endovascular or surgical interventions to assist clinical maturation. However, the effect of assisted maturation on long-term postmaturation AVF outcomes is poorly studied. In this retrospective analysis, the authors analyzed the US Renal Data System to identify elderly patients who underwent AVF creation after initiation of hemodialysis, and whose AVF was used successfully for dialysis with or without assisted maturation. Their analysis of the relationship between the number of prematuration AVF interventions and postmaturation AVF outcomes found a positive association between the number of prematuration interventions and the likelihood of primary patency loss and frequency of interventions after maturation. These findings highlight the high burden of costly interventions to assist clinical maturation for successful AVF use.

Abstract

Background About half of arteriovenous fistulas (AVFs) require one or more interventions before successful dialysis use, a process called assisted maturation. Previous research suggested that AVF abandonment and interventions to maintain patency after maturation may be more frequent with assisted maturation versus unassisted maturation.

Methods Using the US Renal Data System, we retrospectively compared patients with assisted versus unassisted AVF maturation for postmaturation AVF outcomes, including functional primary patency loss (requiring intervention after achieving AVF maturation), AVF abandonment, and frequency of interventions.

Results We included 7301 patients ≥67 years who initiated hemodialysis from July 2010 to June 2012 with a catheter and no prior AVF; all had an AVF created within 6 months of starting hemodialysis and used for dialysis (matured) within 6 months of creation, with 2-year postmaturation follow-up. AVFs matured without prior intervention for 56% of the patients. Assisted AVF maturation with one, two, three, or four or more prematuration interventions occurred in 23%, 12%, 5%, and 4% of patients, respectively. Patients with prematuration interventions had significantly increased risk of functional primary patency loss compared with patients who had unassisted AVF maturation, and the risk increased with the number of interventions. Although the likelihood of AVF abandonment was not higher among patients with up to three prematuration interventions compared with patients with unassisted AVF maturation, it was significantly higher among those with four or more interventions.

Conclusions For this cohort of patients undergoing assisted AVF maturation, we observed a positive association between the number of prematuration AVF interventions and the likelihood of functional primary patency loss and frequency of postmaturation interventions.

  • arteriovenous fistula
  • arteriovenous access
  • vascular access

Current national vascular access guidelines and the Centers for Medicare and Medicaid Services, the primary payer for ESKD services, promote an arteriovenous fistula (AVF) as the preferred type of vascular access for hemodialysis because of its association with lower rates of infection and mortality compared with arteriovenous graft (AVG) and central venous catheter (CVC).1,2 Successful AVF use requires a multistep process including surgical creation, physiologic maturation (i.e., an adequate increase in blood flow and diameter), and successful cannulation.3 Increasing AVF use—a priority of national vascular access recommendations for the past two decades—has been limited by the unexpectedly high rate of AVF maturation failure, ranging from 30% to 60%.4–7 Approximately half of new AVFs require one or more interventions to promote their maturation before successful use for dialysis (“assisted maturation”). Two small studies from one to two medical centers reported that AVFs with assisted maturation were associated with more frequent interventions to maintain patency after maturation and had greater AVF abandonment compared with AVFs with unassisted maturation.8,9 These pilot observations suggest that assisted AVF maturation may be associated with adverse consequences on long-term AVF outcomes, but have not been confirmed in larger patient cohorts.

The goal of this study was to assess, in a nationally representative cohort of patients on hemodialysis in the United States, whether the presence and number of interventions to assist AVF maturation are associated with postmaturation long-term AVF outcomes in a national cohort of patients on hemodialysis aged ≥67 years who are initiating hemodialysis with a CVC.

Methods

Data Sources and Study Population

The cascade of patients selected using the study criteria is depicted in Figure 1. Our primary data source was derived from the US Renal Data System (USRDS) standard analytic files between July 1, 2010 and June 30, 2015. Patients with ESKD who initiated hemodialysis between July 1, 2010 and June 30, 2012 were eligible for inclusion in the study. We restricted our analysis to patients aged ≥67 years to ensure the availability of 2 years of Medicare information before reaching ESKD. We further limited the cohort to patients who initiated hemodialysis with a CVC and without AVF or AVG surgeries in the 2 years preceding dialysis initiation (representing approximately 60% of all patients on incident dialysis who are at high risk of long-term CVC use and adverse outcomes). Finally, we restricted the patient population to those who had an AVF placed within 6 months of dialysis start and successfully used AVF for dialysis (matured) in the subsequent 6 months. The details of cohort formation are listed in Supplemental Figure 1. The final study cohort (7301 patients) was followed from AVF maturation (study baseline) to abandonment, death, or the end of 2 years after AVF maturation (administrative censoring), whichever occurred first (Figure 1). The mean follow-up time for primary patency loss and abandonment was 6.9 and 15.5 months, respectively. Institutional review board approval was not required because all data used for this study were encrypted and deidentified.

Figure 1.
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Figure 1.

Patient cascade of the study cohort initiating hemodialysis (HD) with a CVC and a subsequent AVF placement and maturation.

Variables of Interest

The main study exposure was whether the patient had an unassisted or assisted AVF maturation before its successful use, i.e., whether there was an antecedent AVF intervention to facilitate maturation. AVF maturation was ascertained by using the first vascular access modifier code “V7” reported from the institutional details claims file or the first AVF used with two needles reported from the CrownWeb clinical file. The V codes are reported monthly and reflect the vascular access type on the last hemodialysis session of each month. These reports are completed by the dialysis nurses at the dialysis unit. If a patient has both a CVC and AVF, the patient is reported as using a CVC. The most common type of assisted AVF maturation was percutaneous angioplasty (approximately 80%), but a small proportion of patients underwent a surgical revision. Procedures were identified by using codes listed in Supplemental Table 1, which have been previously described.10 Patients were considered to have assisted AVF maturation if they underwent at least one intervention before successful use. If not, they were considered to have unassisted AVF maturation.

We examined several postmaturation clinical AVF outcomes:

  1. Functional primary patency loss was defined as the requirement for at least one AVF intervention after its maturation.

  2. AVF abandonment after successful maturation (i.e., secondary patency loss) was defined as the use of a CVC for dialysis on three consecutive months or placement of new AVF or AVG. The date of AVF abandonment was attributed to the first month after AVF maturation during which CVC use was reported.

  3. Frequency of AVF interventions during post-AVF maturation follow-up was defined as the performance of any percutaneous or surgical interventions during the period after AVF maturation, as previously described (Supplemental Table 1).11

  4. Primary functional AVF patency was defined as time from maturation to first postmaturation intervention in patients who had functional primary patency loss.

  5. Secondary functional AVF patency was defined as time from maturation to abandonment in patients who had AVF abandonment.

The Medical Evidence Record data at initiation of dialysis recorded aged patient (years) at ESKD onset, race (black, white, or other), sex, and proxies for health status such as underlying cause of ESKD (diabetes, GN, hypertension, cystic kidney, or other), poor functional status (amputation, inability to ambulate or transfer, needs assistance with daily activities, and being institutionalized), laboratory values (hemoglobin, serum albumin, and eGFR), duration of pre-ESKD nephrology care (no care, <6, 6–12, or >12 months), and body mass index. Hemodialysis facility type and profit status were ascertained from the USRDS facility file. Comorbidity data in the 2 years before initiation of dialysis were extracted from pre-ESKD Medicare data, as previously published.12,13 The major comorbid conditions extracted were diabetes, hypertension, coronary artery disease, congestive heart failure, peripheral vascular disease, cerebrovascular disease, stroke, chronic obstructive pulmonary disease, cancer, depression, and dementia. A specialized comorbidity index, calculated to measure the severity of patient comorbid conditions on the basis of the presence or absence of nonrenal disease, and validated in patients on dialysis was used.14 Duration of CVC dependence before AVF maturation was calculated from dialysis initiation with a CVC until AVF use.

Statistical Analyses

Baseline patient characteristics and practice patterns were compared between patients with or without an assisted AVF maturation, using Pearson chi-squared tests for categorical variables, and t test or nonparametric Wilcoxon rank-sum test for continuous variables. Competing events is a crucial consideration in studies of older patients on hemodialysis because of the high mortality risk. Methods that fail to account for the presence of death can yield biased estimation.15 We therefore treated death before the AVF outcome of interest as a competing risk, and classified patients into three mutually exclusive groups according to whether they experienced AVF functional primary patency loss or abandonment: (1) patient experienced any outcome of interest, (2) patient died before experiencing any outcome of interest, and (3) patient did not experience any outcome of interest or die. We used discrete-time multinomial logistic models to explore the possible association between the presence and frequency of assisted AVF maturation intervention(s) and the long-term AVF outcomes, including AVF functional primary patency loss and abandonment. The association of the presence and frequency of assisted AVF maturation intervention(s) and frequency of access interventions after maturation was examined using negative binomial regression. The final regression models were adjusted for age, sex, race, Liu comorbidity index, functional status, facility type, facility chain status, and log time of CVC dependency. Furthermore, we used restricted cubic splines produced by %RCS_REG to test the assumption of a linear relationship between prematuration interventions as a continuous variable and log odds ratio (OR) of AVF primary patency loss.16 The restricted cubic spline methodology provides a flexible model to examine the adjusted effect of a continuous predictor on an outcome, and allows for visualization of the relationship without prior knowledge of the functional form of the association. All statistical tests were two-sided, and a P value <0.05 was considered statistically significant.

Results

Baseline Patient Characteristics

The study cohort included 7301 patients, of whom 4091 (56%) had unassisted AVF maturation and 3210 (44%) had assisted maturation. Table 1 summarizes the demographic and clinical characteristics of the study population, sorted by unassisted versus assisted AVF maturation status. Compared with patients with unassisted AVF maturation, those with assisted maturation were more likely to be women, black, diabetic, and have higher comorbidity scores and body mass index, and to be dialyzed at for-profit dialysis centers (Table 1). A requirement for one, two, three, and four or more interventions before successful AVF maturation was observed in 23%, 12%, 5%, and 4% of patients, respectively (Supplemental Table 2).

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Table 1.

Baseline patient demographics, comorbid conditions, functional status, laboratory values, and care patterns in patients with unassisted versus assisted AVF maturation

Primary AVF Patency Loss

For patients with functional primary AVF patency loss, the mean and median follow-up time was 6.9 and 3 months from AVF maturation, respectively. The mean and median follow-up time was 7.7 and 4 months, respectively, for the unassisted maturation group and 6 and 3 months, respectively, for the assisted maturation group. Functional primary AVF patency loss was significantly greater in patients with assisted AVF maturation than those with unassisted AVF maturation (82% versus 74%; OR, 1.61; 95% confidence interval [95% CI], 1.37 to 1.89). Among the patients with assisted AVF maturation, the likelihood of functional primary patency loss was increasingly greater, as the number of prematuration interventions increased from one to four or more (Supplemental Table 2). Specifically, the functional primary patency loss was 74% for AVFs with unassisted maturation, 80% for AVFs requiring one assisted intervention, 82% for those with two interventions, 85% for those with three interventions, and 87% for those with four or more prematuration interventions. Using multinomial logistic analysis, the adjusted OR for functional primary patency loss (relative to patients with unassisted AVF maturation) increased from 1.27 (95% CI, 1.06 to 1.52) in patients with one intervention to 3.46 (95% CI, 1.96 to 6.11) in those with four or more interventions (Figure 2A). Among the patients with primary AVF patency loss, the mean functional primary patency (time from AVF maturation to the first postmaturation intervention) was about 1 month shorter in patients with assisted AVF maturation versus those with unassisted maturation (P<0.001) (Supplemental Figure 2, Table 2). The functional primary AVF patency decreased from 4.0–3.7 to 3.5–2.7 months, as the number of prematuration interventions increased from one to two, to three to four or more. To better visualize this relationship, we created a restricted cubic spline plot between the number of prematuration assisted AVF interventions and the natural logarithm of the adjusted OR of primary AVF patency loss (Figure 3). This analysis found a positive linear relationship between the number of AVF assisted maturation interventions and increased likelihood of functional primary patency loss, i.e., there was no specific threshold (exact number of interventions) at which the risk of functional primary patency loss increased or decreased significantly.

Figure 2.
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Figure 2.

Adjusted ORs of AVF functional primary loss and abandonment and risk ratios (RRs) of frequency of postmaturation intervention. (A) Functional primary patency loss, (B) AVF abandonment, and (C) frequency of postmaturation intervention. Adjusted for age, sex, race, Liu comorbidity index, functional status, facility type, facility chain status, and log time of CVC dependency. LCL, lower confidence limit; UCL, upper confidence limit.

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Table 2.

Primary AVF functional patency and AVF abandonment, sorted by the number of prematuration interventions

Figure 3.
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Figure 3.

Restricted cubic spline plot of the adjusted natural log OR of AVF functional primary patency loss versus the number of prematuration interventions with five knots. The curve ends the 99% percentile of the number of prematuration interventions, i.e., five. The light dotted curves present the 95% CIs. The straight green line is the reference line of OR of 1. Adjusted for age, sex, race, Liu comorbidity index, functional status, facility type, facility chain status, and log time of CVC dependency. The dose-response association was not significantly nonlinear (P=0.39).

AVF Abandonment

For patients with AVF abandonment, the mean and median follow-up time was 16 and 20 months from AVF maturation, respectively. The mean and median follow-up time was 15 and 20 months, respectively, for the unassisted maturation group and 16 and 21 months, respectively, for the assisted maturation group. AVF abandonment at 2 years was similar in patients with assisted versus unassisted AVF maturation (24% versus 27%; OR, 0.99; 95% CI, 0.88 to 1.12) (Supplemental Figure 2, Supplemental Table 2). The rate of AVF abandonment ranged from 24% to 27% in patients with one to four or more prematuration interventions, respectively. In multinomial logistic analysis, only AVFs with four or more prematuration interventions were significantly associated with greater AVF abandonment compared with AVFs with unassisted maturation (OR, 1.44; 95% CI, 1.07 to 1.95) (Figure 2B). Among patients with AVF abandonment, the time from AVF maturation to abandonment was similar among patients with zero, one, two, three, or four or more prematuration assisted interventions (Table 2).

Frequency of Postmaturation AVF Interventions

The mean number of postmaturation interventions was significantly greater in AVFs requiring assisted versus unassisted maturation (3.9±4.0 versus 2.9±3.4; relative risk, 1.31; 95% CI, 1.21 to 1.41). Among the patients with assisted AVF maturation, there was an increasingly higher frequency of postmaturation interventions associated with an increasing number of prematuration interventions (Figure 4, Table 3). Specifically, patients with one prematuration intervention had a mean of 3.4±3.6 postmaturation interventions after maturation, whereas those with four or more prematuration interventions had 5.1±4.9 postmaturation interventions. The rate of postmaturation AVF interventions was 7.1±18.8 per year in the patients with unassisted AVF maturation versus 6.0±12.4 per year in those with assisted maturation (Figure 4, Table 3). Because the distribution of the mean intervention rates was highly skewed (SD greater than the means), the median is a more accurate reflection of the frequency of postmaturation interventions (Table 3). Using multinomial logistic analysis, the adjusted relative rate of postmaturation interventions in comparison to patients with unassisted AVF maturation increased from 1.17 (95% CI, 1.07 to 1.28) for patients with one prematuration intervention to 1.93 (95% CI, 1.61 to 2.32) in those with four or more prematuration interventions (Figure 2C).

Figure 4.
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Figure 4.

Cumulative number of interventions by number of prematuration interventions.

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Table 3.

Number and rate of postmaturation AVF interventions, sorted by the number of prematuration interventions

Sensitivity Analyses

We conducted three sensitivity analyses to test the robustness of our results. First, we determined whether our estimation of the association of assisted AVF maturation with postmaturation AVF outcomes would change without accounting for the competing risk of death (Supplemental Table 3). Second, we excluded the group of patients who experienced the highest frequency of prematuration interventions (99th percentile or greater), to quantify the effect of outliers of interventions on AVF outcomes (Supplemental Table 4). Third, we tested the assumption in our primary analysis that all interventions occurred during the month of AVF maturation were interventions after maturation. In the sensitivity analysis, we assumed the opposite, i.e., that all interventions during that month of maturation represented prematuration interventions (Supplemental Table 5). In general, under each of these sensitivity analyses, the association of assisted maturation with postmaturation AVF outcomes was similar to that observed in the primary analysis (Figure 2). However, the significance of the association of AVF abandonment with four or more prematuration interventions was lost when the top 1% of patients were excluded.

Discussion

Using a large, national cohort of United States patients initiating hemodialysis with a CVC, we determined the association of assisted AVF maturation with several postmaturation outcomes. Our analyses yielded several notable findings. First, nearly half of the patients required assisted AVF maturation, in agreement with several recent reports.17 Second, functional primary AVF patency loss was associated with a greater number of prematuration interventions. Third, AVF abandonment was similar between AVFs with unassisted or assisted maturation. Fourth, the frequency of postmaturation interventions was directly associated with the number of prematuration interventions. Collectively, these findings highlight the great frequency of assisted AVF maturation, and its association with postmaturation functional primary AVF patency loss and the frequency of postmaturation interventions required to maintain patency.

A functional and durable vascular access is critical for successful long-term delivery of hemodialysis. Although AVFs are the preferred access type because of their association with lower rates of infection and patient mortality compared with AVGs and CVCs,18–20 recent multicenter United States studies highlight the great frequency of new AVFs that fail to mature.4 To improve clinical AVF maturation, nephrologists and interventional radiologists have become more aggressive in interventions to salvage immature AVFs that fail to mature.10 The multicenter Hemodialysis Fistula Consortium Study, which enrolled 602 patients with a new AVF from 2010 to 2013, observed that only 44% achieved unassisted AVF maturation.21 In agreement with that study, our study of a national incident hemodialysis population aged ≥67 years observed that only 56% of AVFs that matured did so without a prior intervention. In comparison, recent international data from Dialysis Outcomes and Practice Patterns Study has highlighted large variations in successful AVF use among countries.22 Successful AVF use (defined as using a newly created arteriovenous access for 30 or more continuous days) was 87% in Japan, 67% in Europe and Australia/New Zealand, and only 64% in the United States.22 Unfortunately, Dialysis Outcomes and Practice Patterns Study did not report the proportion of AVFs that mature unassisted. Our study also demonstrated several baseline demographic factors that may serve as markers of poor vascular health such as sex, black race, and diabetes. Female sex has been demonstrated in a number of studies to be associated with poor AVF maturation and lower AVF use.23

Two previous small studies reported that assisted AVF maturation was associated with a greater likelihood of loss of functional primary AVF patency and abandonment after maturation.8,9 In agreement with the first observation, a quantitative analysis in our study revealed a linear relationship between the number of AVF assisted maturation interventions and the likelihood of functional primary patency loss. In the unassisted AVF maturation group, 74% still required postmaturation interventions versus 79%–86% in the assisted maturation groups. After the adjustment, the assisted group was 31% more likely to have postmaturation interventions. The relatively modest differences between the two groups were magnified when hazard ratios were calculated. In contrast to the two previous single-center studies,8,9 we found no association between assisted maturation and AVF abandonment. This discrepancy may reflect a greater recent willingness to utilize repeated interventions in the United States to maintain long-term AVF patency for dialysis. This may be consistent with the tripling of AVF angioplasty rates (from 0.16 to 0.47 per patient-year) between 1998 and 2007,24 and is facilitated by a generous Medicare reimbursement for such procedures. Thamer et al.10 reported that Medicare costs for invasive imaging and endovascular procedures exceeded $1 billion annually from 2011 to 2013. Of interest, our baseline care patterns also suggest that processes of care to promote AVF maturation may differ by facility type and profit status, as patients from for-profit centers are more likely to have assisted maturation as compared with those from nonprofit centers. This is an observation that merits further investigation.

Assisted AVF maturation may have other deleterious consequences. First, it is associated with prolonged CVC dependence. In one recent study, the mean duration of catheter dependence was 99 days in patients with unassisted AVF maturation, compared with 159 days in those with assisted AVF maturation.8 Similarly, our study found that CVC dependence was 1.2 months longer in patients with assisted AVF maturation. Second, the requirement for multiple assisted maturation procedures translates into greater costs for vascular access management. In agreement with this finding, a recent study evaluating Medicare costs from patients on hemodialysis in the United States aged ≥67 years reported that the cost of access management was twice as high in patients with primary AVF patency loss after successful use compared with those who maintained functional primary patency after successful AVF use.10 Third, patient quality of life suffers from repeated endovascular and surgical interventions, which are costly, time-consuming, painful, and disruptive to their dialysis therapy.

Why might assisted maturation in general, and the number of prematuration AVF interventions specifically, be associated with adverse postmaturation AVF outcomes? There are two possible explanations. First, the intervention itself (most commonly, an angioplasty) causes direct vascular injury, which in turn accelerates neointimal hyperplasia and leads to early recurrence of stenosis.25 We also recognize that the area being treated is most likely preventing the AVF from becoming functional. Alternatively, AVFs requiring assisted maturation may simply reflect the use of poor quality native vessels, which are less likely to promote adequate physiologic AVF maturation, and therefore more likely to require interventions to help their maturation. In other words, both the number of assisted maturation interventions and the frequency of interventions required to maintain AVF patency after its maturation may be surrogate markers of the quality of the native vessels.

To our knowledge, the overall high rate of AVF intervention after maturation has not been previously been reported in a national hemodialysis population. The 2006 Kidney Disease Outcomes Quality Initiative (KDOQI) vascular access guidelines promoted AVF placement in the majority of patients on dialysis (“Fistula First” approach), but this policy may need to be revisited in the older population, as our data suggests a high burden of AVF maintenance interventions once matured for dialysis use. The new 2018 KDOQI Vascular Access Practice Guidelines move away from a Fistula First approach, and emphasize a more patient-centered approach and development of an ESKD life plan.26 A significant component of this life plan is to select the most appropriate vascular access for each patient that will be “reliable,” “complication free to provide prescribe dialysis,” and “most suitable for the patient’s needs.”26 Patient selection for AVF placement is an important factor, particularly for the older population where life expectancy, quality of life, and likelihood of AVF maturation need to be carefully considered.

Our study has several limitations. First, because we used administrative Medicare data, it focused on older patients (≥67 years), and our findings may not be generalized to the younger hemodialysis population. However, they are relevant to a large segment of United States patients on incident hemodialysis who are ≥65 years of age. In the 2018 USRDS report, 61% of patients aged 65–74 years and 64% of patients aged >75 years initiated hemodialysis with a CVC only.27 Second, because this study was observational and used a national administrative database, the rationale for the scheduling of assisted maturation procedures and postmaturation interventions could not be ascertained. Third, the V codes used to determine type of vascular access in use have not been validated. Fourth, we were unable to determine the location of the AVF (upper arm versus lower arm) or AVF configuration, factors that may affect the likelihood of clinical maturation. Recent DOPPS data found that in the United States approximately 70% of AVFs are currently created in the upper arm.22 Fifth, our cohort was limited to AVFs that matured among patients initiating dialysis with a CVC. Thus, our results should not be extrapolated to patients undergoing AVF creation before initiation of dialysis. Sixth, our study lacked a comparison group with AVFs that did not mature, with or without attempts at assistance. Finally, there was likely residual confounding, as it was not possible to adequately adjust for all patient- or systems-based factors that may affect our measured clinical vascular access outcomes. In contrast, the strengths of this study include its use of a large national database that is representative of vascular access practices across the United States, the use of V codes to ascertain the access type in use, and the use of prespecified definitions of clinical AVF outcomes.

What are the clinical implications of this study? First, it highlights the urgent need for novel therapies to mitigate vascular injury after endovascular procedures. Unfortunately, to date, no such therapies have been proven effective. Second, proper selection of patients for AVF placement is crucial. It is likely that some patients requiring assisted AVF maturation have poor native vessels. The clinician must consider the option of AVG placement in some patients, to minimize the need for assisted AVF interventions, and shorten CVC dependence.8,11 In this regard, it would be helpful to develop algorithms that reliably predict AVFs likely to require multiple procedures to assist AVF maturation, as this study demonstrates a linear relationship between number interventions and increased likelihood of functional primary patency loss. Our results from a national renal dialysis database demonstrate that a substantial proportion of AVFs created in patients initiating dialysis with a CVC require assisted maturation before successful use for dialysis. Although assisted maturation may be a prerequisite for achieving successful AVF use for dialysis in many patients, this study highlights the associated burden of procedures after AVF maturation. Collectively, these findings suggest the need for better patient selection for AVF placement, and novel pharmacologic therapies to mitigate the vascular damage after AVF interventions.

Disclosures

Dr. Allon is a consultant for CorMedix. Dr. Lee is a consultant for Proteon Therapeutics, Boston Scientific, and Merck. Dr. Thamer is a consultant for Proteon Therapeutics. Ms. Qian and Dr. Zhang have no financial disclosures to report.

Funding

Dr. Allon is supported by a grant from the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK; 1R21DK104248-01A1). Dr. Lee is supported by a grant from the NIDDK (2R44DK109789-01), a grant from the National Heart, Lung, and Blood Institute (1R01HL139692-01), and a Veterans Affairs Merit Award (1I01BX003387-01A1). Dr. Thamer is supported by grants from the NIDDK (1R21DK104248-01A1) and from the Agency for Healthcare Research and Quality (AHRQ; R01-HS-021229). Ms. Qian is supported by grants from the NIDDK (1R21DK104248-01A1) and AHRQ (R03-HS-022931). Dr. Zhang is supported by a grant from the NIDDK (1R21DK104248-01A1) and a Patient-Centered Outcomes Research Institute Dissemination and Implementation Award (DI-1607-35615).

Supplemental Material

This article contains the following supplemental material online at http://jasn.asnjournals.org/lookup/suppl/doi:10.1681/ASN.2019030318/-/DCSupplemental.

Supplemental Table 1. Codes of surgical and endovascular AVF procedures.

Supplemental Table 2. AVF functional primary patency loss and abandonment, by the number of prematuration interventions.

Supplemental Table 3. ORs and 95% CIs of AVF functional primary and abandonment without accounting for the competing risk of death.

Supplemental Table 4. ORs of AVF functional primary and abandonment and risk ratios (RRs) of frequency of postmaturation AVF interventions, excluding patients with frequency of prematuration interventions ≥99 percentile.

Supplemental Table 5. ORs of AVF functional primary and abandonment and risk ratios (RRs) of frequency of postmaturation intervention, after counting interventions in the same month of maturation as prematuration interventions.

Supplemental Figure 1. Cohort derivation.

Supplemental Figure 2. Cumulative incidence functions (CIFs) of AVF long-term outcomes by prematuration interventions. (A) Functional primary patency loss by assisted versus unassisted maturation, (B) functional primary patency loss by frequency of prematuration interventions, (C) abandonment by assisted versus unassisted maturation, and (D) abandonment by frequency of prematuration interventions. P values were obtained using the Gray test for equality of CIF.

Acknowledgments

Dr. Lee, Dr. Thamer, Ms. Qian, and Dr. Allon designed the study. Dr. Lee, Ms. Qian, Dr. Zhang, Dr. Thamer, and Dr. Allon analyzed the data. Ms. Qian made the figures. Dr. Lee, Dr. Thamer, Dr. Allon, Ms. Qian, and Dr. Zhang drafted and revised the paper. All authors approved the final version of the manuscript.

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

  • See related editorial, “Fistula Interventions: Less Is More,” on pages 2040–2042.

  • Copyright © 2019 by the American Society of Nephrology

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Journal of the American Society of Nephrology: 30 (11)
Journal of the American Society of Nephrology
Vol. 30, Issue 11
November 2019
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Long-Term Outcomes of Arteriovenous Fistulas with Unassisted versus Assisted Maturation: A Retrospective National Hemodialysis Cohort Study
Timmy Lee, Joyce Zhang Qian, Yi Zhang, Mae Thamer, Michael Allon
JASN Nov 2019, 30 (11) 2209-2218; DOI: 10.1681/ASN.2019030318

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Long-Term Outcomes of Arteriovenous Fistulas with Unassisted versus Assisted Maturation: A Retrospective National Hemodialysis Cohort Study
Timmy Lee, Joyce Zhang Qian, Yi Zhang, Mae Thamer, Michael Allon
JASN Nov 2019, 30 (11) 2209-2218; DOI: 10.1681/ASN.2019030318
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