A meta-analysis of the hemodynamic and echocardiographic changes following arteriovenous fistula ligation in chronic kidney disease patients

Abstract

Arteriovenous fistulas (AVFs) are the preferred method for establishing long-term vascular access in patients undergoing hemodialysis; however, high-flow AVFs may increase cardiovascular strain after kidney transplantation, often necessitating fistula closure. Currently, no established guideline exists for managing high-flow fistulas in post-transplant patients with stable kidney function, and available studies report heterogeneous results with small sample sizes and different methodologies. We performed a systematic search of PubMed, Cochrane, and Embase up to December 2024 for observational studies and randomized controlled trials comparing AVF ligation versus maintenance in patients with end-stage kidney disease. The meta-analysis was conducted using Cochrane’s RevMan software using mean difference (MD) and 95% confidence interval. Twelve studies including 844 patients were analyzed, of whom 409 (48%) underwent AVF ligation, with follow-up ranging from 3 to 62.5 months. AVF ligation was associated with a significant reduction in left ventricular mass index (MD −10.92 g/m²; 95% confidence interval −17.84 to −3.99; p = 0.007) and cardiac index (MD −0.56 L/min/m²; 95% confidence interval −1.05 to −0.07; p = 0.03), indicating attenuation of the hyperdynamic circulatory state related to a persistent AVF. No significant differences were observed in left ventricular ejection fraction or blood pressure parameters. Serum creatinine levels were modestly reduced following AVF ligation (MD −0.12 mg/dL; 95% confidence interval −0.22 to −0.03; p = 0.02), while estimated glomerular filtration rate remained unchanged. Overall, AVF ligation was associated with favorable cardiac remodeling reflected by reductions in left ventricular mass and cardiac output, with supportive changes in secondary echocardiographic parameters and no apparent deterioration in renal function.

Keywords

Arteriovenous fistula blood pressure end-stage renal disease hypertension shunt

Introduction

Arteriovenous fistulas (AVFs) are the gold standard for establishing long-term vascular access in patients with end-stage kidney disease (ESKD) undergoing hemodialysis, offering superior patency and lower infection rates compared to alternative access options.¹ However, their physiological impact extends beyond dialysis access. The presence of a functioning AVF creates a low-resistance shunt, resulting in increased venous return, elevated cardiac output, and chronic volume overload. Over time, this can lead to adverse cardiac remodeling, including left ventricular hypertrophy, left atrial dilation, and elevated levels of natriuretic peptides, all of which reflect increased cardiovascular strain.^2,3

Patients with a successful kidney transplant or renal recovery no longer require dialysis but often continue to have a functioning AVF. The ongoing hemodynamic burden imposed by high-flow AVFs in such patients raises concerns regarding their potential contribution to cardiovascular morbidity.^4,5 As a result, elective AVF closure has been proposed as a strategy to alleviate cardiac stress in patients with stable renal function. The physiological rationale is that closure of the shunt should reduce preload and reverse elements of volume overload.³

Despite these considerations, no clinical guidelines currently provide recommendations for the management of AVFs in patients with stable graft function or no ongoing dialysis.⁶ Clinical practice remains heterogeneous, often influenced by concerns regarding future dialysis access rather than cardiovascular optimization.⁷ Moreover, although individual studies have explored the impact of AVF closure on various cardiac and hemodynamic parameters, the results are inconsistent.

Therefore, we conducted a systematic review and meta-analysis comparing hemodynamic and echocardiographic changes following AVF closure versus persistence.

Methods

This systematic review and meta-analysis was conducted in accordance with the recommendations outlined in the Cochrane Collaboration Handbook for Systematic Reviews of Interventions⁸ and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)⁹ statement guidelines (Supplemental Methods 1). The protocol of this study was prospectively registered in the International Prospective Register of Systematic Reviews PROSPERO (CRD420251080879).

Eligibility criteria

Inclusion was restricted to studies meeting all the following eligibility criteria: (1) RCTs or observational studies; (2) including patients with CKD post kidney transplant or with stable renal function with an AVF; (3) comparing AVF closure versus persistence; (4) analyzing at least one of the pre-specified clinical outcomes of interest. There were no restrictions on follow-up duration. Studies were excluded if they: (1) were conference abstracts, letters, editorials, expert opinions, case reports, or reviews; (2) had no outcomes of interest; and (3) had overlapping study populations. The eligibility criteria for each study are in Supplemental Table 1.

Search strategy and data extraction

A comprehensive literature search was conducted across PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from database inception through December 2024. The search strategy incorporated terms such as: (“Arteriovenous Fistula” OR “AV Fistula” OR AVF OR “Arteriovenous Shunt” OR “Arteriovenous Access”) AND (Closure OR Ligation) AND (Echo OR Cardiac OR Heart). References of all eligible full-text articles and relevant prior systematic reviews were manually screened through backward snowballing.¹⁰

Two independent reviewers (M.E. and M.Z.) screened studies for eligibility, extracted data, and conducted quality assessments using predefined criteria. Any discrepancies were resolved through discussion and consensus. Data on arteriovenous fistula flow volume were extracted when reported; however, access flow measurements were inconsistently available across studies and therefore could not be pooled for quantitative analysis.

Endpoints

The primary structural outcome was left ventricular mass index (LVMI).

The primary hemodynamic outcome was cardiac index.

Secondary outcomes included additional echocardiographic parameters reflecting left ventricular geometry (e.g. LVEDDi, posterior wall thickness), renal function parameters, blood pressure measurements, and pro-B-type natriuretic peptide (NT-proBNP).

Risk of Bias assessment

Two authors (M.A. and V.R.), with no affiliation with the included trials, independently assessed the risk of bias for each of the included studies. Cochrane Risk of Bias Tool version 2¹¹ was used for RCTs, while non-randomized studies were evaluated using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool.¹² Disagreements were resolved by consensus between both authors.

Statistical analysis

Mean differences (MD) with 95% confidence intervals were used to compare treatment effects for continuous outcomes. The Cochrane Q test and I² statistics were used to check for differences between studies; a p value less than 0.10 and I² greater than 25% indicated a significant difference. In accordance with the Cochrane Collaboration recommendations, we used an inverse variance random-effects model for the analysis, considering variations between studies. Sensitivity analysis was performed through a leave-one-out strategy to investigate undue influence on the estimate for outcomes with high heterogeneity. Publication bias was assessed via funnel plot asymmetry and Egger’s regression test. Review Manager (RevMan), the Cochrane Collaboration, version 5.4 was used for statistical analysis.

Results

As shown in Figure 1, a total of 2354 records were identified. After full screening, 12 studies met all inclusion criteria, comprising 844 patients, of whom 409 (48%) underwent AVF closure. We included 2 RCTs^3,5 and 10 non-RCTs. Participants had a mean age ranging from 25 to 73 years and were mostly male (33%–86%), with a follow-up period between 3 and 72 months. Indications for closure included high-output heart failure and cosmetic reasons. Arteriovenous fistula types and baseline kidney function are shown in Table 1. The control groups of the RCTs were defined as (1) Kidney‑transplant recipients with a high‑flow AVF (≥1500 mL/min), stable graft function, no pre‑existing severe cardiac failure, and patients who did not receive an immediate fistula ligature were included in the study. They were followed prospectively (clinical assessment + echocardiography) for 24 months for Hetz et al.,⁵ and (2) kidney‑transplant recipients ≥12 months post‑transplant with a functioning AVF and stable graft function who were randomized to no intervention (i.e. the fistula was left patent). They underwent cardiac magnetic resonance (CMR) at baseline and again at 6 months in Rao et al.³

Figure 1.

PRISMA diagram summarizing the study selection procedure.

Table 1.

Baseline characteristics of the included studies.

Study	Design	Population	Indication for closure	Type of AVF	Patent AVF flow mL/min	Closed AVF flow mL/min	Follow-up, months	Number of patients patent AVF, n	No patent AVF, n
Hetz 2020⁵	RCT	Kidney transplant recipient	Prevent high-output HF	3 upper arm and 25 unknown	1.850 ± 48	1800 ± 67	24	14	14
Rao 2019³	RCT	Kidney transplant recipient	Reduce LV mass/cardiac remodeling	17 forearm and 16 upper arm	N/A	N/A	6	27	27
Głowiński 2012¹³	Cohort	Kidney transplant recipient	Cosmetic (50%)/spontaneous thrombosis (44%)	6 forearm and 3 arm	717 ± 209	593 ± 89	3	9	9
Unger 2008¹⁴	Prospective cohort	Kidney transplant recipient	Cardiovascular risk (n = 9)/venous hypertension (n = 7)/cosmetic (n = 1)	7 radioradial and 9 brachial communicating	N/A	N/A	21	14	16
Movilli 2010¹⁵	Prospective cohort	Hemodialysis patients	AVF malfunction	18 brachiobasilic, 7 brachiocephalic	N/A	N/A	6	36	25
Schier 2013¹⁶	Retrospective cohort	Kidney transplant recipient	High-output HF	Radiocephalic: 16; upper arm: 10; others (grafts): 3	2197	850	N/A	84	29
Sheashaa 2004¹⁷	Cohort	Kidney transplant recipient	Spontaneous AV thrombosis	N/A	N/A	N/A	12	34	17
Unger 2004¹⁸	Cohort	Kidney transplant recipient	Cardiac symptoms, venous hypertension, cosmetic	7 radiocephalic, 5 radioradial, 3 brachial communicating, 1 radiobasilic, 1 femorosaphenous	833 ± 458	886 ± 558	21	8	17
De Lima 1999¹⁹	Cohort	Kidney transplant patients	Cosmetic	Arm or forearm	N/A	N/A	14	39	22
Cridlig 2008²⁰	Matched case-control	Kidney transplant recipient	Spontaneous (61%)	N/A	878 ± 411	1350 ± 560	60	38	38
Kolonko 2014²¹	Cohort	Kidney transplant recipients	Cardiovascular risk	N/A	N/A	N/A	72	67	95
Letachowicz 2018²²	Cross-sectional	Hemodialyzed kidney transplant recipients	N/A	N/A	N/A	N/A	62.4	65	97

AVF: arteriovenous fistula; HF: heart failure; LV: left ventricular; N/A: not available; RCT: randomized controlled trial.

Structural cardiac remodeling parameters showed an overall favorable profile. There was a significant decrease in LVMI (MD: −10.92 g/m²; 95% Confidence Interval: −17.86 to −3.99; p = 0.007; I² = 8%; Figure 2(a)), posterior wall diameter (MD: −0.47 mm; 95% Confidence Interval: −1.32 to −0.38; p = 0.022; I² = 57%; Supplemental Figure 1), LVEDDi (MD: −2.11 mm/m²; 95% Confidence Interval: −3.10 to −1.13; p = 0.003; I² = 0%; Supplemental Figure 2) and cardiac index (MD: −0.56 L/min/m²; 95% Confidence Interval: −1.05 to −0.07; p = 0.03; I² = 70%; Figure 2(b)).

Figure 2.

(a) Forest plots for the difference of left ventricular mass index between groups with AVF closure and persistence and (b) Forest plots for the difference of cardiac Index between groups with AVF closure and persistence.

No statistically significant differences were noted for left atrial diameter (MD: −1.91 mm; 95% Confidence Interval: −6.84 to 3.03; p = 0.24; I² = 53%; Supplemental Figure 3) or interventricular septal thickness (interventricular septum: MD: −0.16 mm; 95% Confidence Interval: −1.37 to 1.04; p = 0.72; I² = 68%; Supplemental Figure 4) or in LVEF (MD: −0.10%; 95% Confidence Interval: −2.99 to 2.79; p = 0.093; I² = 49%; Supplemental Figure 5).

NT-proBNP levels were not significantly different between groups in the overall pooled analysis (MD: −1553.5 pg/mL; 95% Confidence Interval: −4314.76 to 1207.76; p = 0.27; I² = 99%; Figure 3). However, subgroup analysis stratified by study design revealed a significant interaction. While the two randomized controlled trials demonstrated a non-significant trend toward NT-proBNP reduction following AVF ligation, the non-randomized cohort study showed a marked decrease. The test for subgroup differences was statistically significant (p < 0.00001), indicating that study design substantially contributed to the observed heterogeneity (Supplemental Figure 6).

Figure 3.

Forest plots for the difference of NT-ProBNP between groups with AVF closure and persistence.

Renal function remained largely stable following AVF closure. Although a small but statistically significant reduction in serum creatinine was observed (MD: −0.12 mg/dL; 95% Confidence Interval: −0.22 to −0.03; p = 0.02; I² = 0%; Figure 4), this change was insufficient to translate into a significant improvement in eGFR calculations (MD: 2.78 mL/min/1.73 m²; 95% Confidence Interval: −3.25 to 8.81; p = 0.24; I² = 2%; Supplemental Figure 7). This likely reflects the limited sensitivity of eGFR formulas to small variations in serum creatinine and suggests preservation rather than meaningful improvement of overall graft function.

Figure 4.

Forest plots for the difference of serum creatinine between groups with AVF closure and persistence.

Regarding blood pressure outcomes, no differences were seen for systolic (MD: −2.47 mmHg; 95% Confidence Interval: −9.57 to 4.63; p = 0.41; I² = 62%; Supplemental Figure 8) or diastolic blood pressure (MD: 1.54 mmHg; 95% Confidence Interval: −3.12 to 6.19; p = 0.44; I² = 69%; Supplemental Figure 9).

Sensitivity analysis and publication bias

Leave-one-out analysis showed that most outcomes, including NT-proBNP, LVMI, LVEDDi, LAD, and eGFR, had stable heterogeneity estimates with no single study substantially reducing I². However, for posterior wall diameter, exclusion of Unger et al.¹⁸ decreased heterogeneity to 8%. In the diastolic blood pressure analysis, removing De Lima et al.¹⁹ reduced heterogeneity to 21%. Heterogeneity in the LVM analysis decreased to 37% with the removal of Rao et al.³ while in the LVEF analysis, exclusion of Cridlig et al.²⁰ reduced heterogeneity to 30%.

Funnel plots and Egger’s regression test showed no evidence of publication bias for LVMI (p = 0.837; Supplemental Figure 10) or LVEF (p = 0.837; Supplemental Figure 11).

Risk of bias assessment

Ten cohort studies were assessed with ROBINS‑I. Four were classified with serious overall risk of bias,^13,15,16,18 and six were moderate. Confounding was serious in four studies and moderate in the remainder; selection of participants was mostly moderate, with one serious judgment.¹³ Missing data were low except for one study with a serious judgment¹⁴ (Supplemental Table 2).

The two randomized trials were assessed using the RoB 2. Rao et al.³ was low risk across all domains. Hetz et al.⁵ had some concerns regarding outcome measurement and reporting, while the randomization processes, adherence, and completeness of outcome data were otherwise of low risk (Supplemental Table 3).

Discussion

In this systematic review and meta-analysis including 12 studies and 844 patients, elective arteriovenous fistula (AVF) ligation was associated with favorable changes in cardiac structure and hemodynamics. Specifically, AVF closure resulted in significant reductions in LVMI and cardiac index, supporting attenuation of the hyperdynamic circulatory state induced by a persistent arteriovenous shunt. In contrast, left ventricular ejection fraction and blood pressure parameters remained unchanged, suggesting that AVF ligation primarily affects preload-related remodeling rather than intrinsic systolic function. Although individual studies reported reductions in NT-proBNP levels, pooled NT-proBNP did not demonstrate a consistent decrease across studies, highlighting substantial heterogeneity in biomarker responses.³

The physiological basis for these findings lies in the hemodynamic burden imposed by a functioning AVF. Creation of an AVF establishes a low-resistance shunt that reduces systemic vascular resistance and increases venous return, resulting in an immediate compensatory rise in cardiac output and cardiac index, as originally demonstrated by Guyton and Sagawa.^23,24 This hyperdynamic circulatory state enhances diastolic filling and increases LVEDDI through the Frank-Starling mechanism, promoting biatrial and biventricular dilation.²⁵ Chronic exposure to sustained volume overload ultimately leads to eccentric hypertrophy and elevation of LVMI.²⁶ AVF ligation interrupts this pathological shunt physiology, reduces preload and wall stress, and thereby facilitates favorable reverse remodeling and normalization of cardiac index.^23–26

The importance of access flow in mediating these effects is supported by studies in hemodialysis populations undergoing AVF flow-reduction procedures, such as surgical banding or revision.²⁷ These investigations have demonstrated reductions in cardiac output, left ventricular mass, and natriuretic peptide levels following access flow modification, indicating that AVF-related cardiac remodeling is largely flow-dependent and reversible.^27–29 Compared with complete ligation in kidney transplant recipients, flow-reduction strategies in dialysis patients provide mechanistic confirmation that shunt burden is a modifiable determinant of cardiac strain.^27,28 These findings reinforce the pathophysiological link between access flow and cardiovascular remodeling and support the generalizability of flow-mediated cardiac effects across patient populations.^3,27–29

In the present meta-analysis, however, quantitative AVF flow measurements were inconsistently reported across included studies, precluding pooled analysis or formal correlation with cardiac output or cardiac index. Several studies described high-flow fistulas qualitatively or based on clinical criteria such as high-output heart failure, while others did not report access flow at all. This limitation restricts further exploration of flow-dependent effects in transplant recipients.

Beyond structural and hemodynamic remodeling, biomarker responses following AVF ligation were less consistent. Although both randomized controlled trials reported significant reductions in NT-proBNP, pooled analyses including observational data did not reach statistical significance, largely due to substantial heterogeneity.^3,5 Subgroup analyses demonstrated a significant interaction between study design and effect size, suggesting that observational studies may overestimate biomarker changes or reflect differences in baseline heart failure burden, AVF flow characteristics, and timing of biomarker assessment.

The present meta-analysis combined evidence from randomized controlled trials and observational cohort studies, which differ in methodological rigor and susceptibility to bias. While inclusion of observational studies increased sample size and external validity, it also introduced potential residual confounding. Notably, both randomized controlled trials demonstrated consistent reductions in cardiac index and LVMI following AVF ligation, supporting a causal relationship between fistula closure and attenuation of the hyperdynamic cardiac state.^3,5 Although larger observational studies contributed substantially to pooled estimates, the concordant direction of effect across study designs reinforces the robustness of the main findings, while emphasizing the need for cautious interpretation.

Our results are consistent with previous investigations evaluating the cardiovascular impact of persistent AVFs in kidney transplant recipients. Prior studies have demonstrated that maintenance of a functioning AVF after transplantation may contribute to left ventricular hypertrophy, chamber dilation, and a hyperdynamic circulatory state, whereas fistula ligation has been associated with reductions in LVMI, chamber volumes, and cardiac index.^30,31 Variability in reported benefit likely reflects differences in baseline cardiovascular remodeling, access flow characteristics, patient selection, and follow-up duration. Collectively, these data support the concept that AVF-related hemodynamic burden represents a modifiable contributor to cardiac strain in selected post-transplant patients.

While AVF closure appears beneficial for cardiac remodeling, certain patients may still benefit from maintaining vascular access, particularly those at high risk of graft failure or future dialysis requirement. Accordingly, decisions regarding ligation should be individualized based on patient-specific factors, including allograft stability, access flow rate, and echocardiographic parameters. Preoperative evaluation using dynamic AVF occlusion testing, echocardiography, and assessment of glomerular filtration rate trajectories may assist in identifying patients most likely to benefit from closure.^32–34

A recent consensus statement from the Vascular Access Society and the European Society of Organ Transplantation emphasizes individualized decision making regarding post-transplant AVF management, particularly in patients with stable graft function and evidence of cardiovascular strain, and discourages routine fistula closure in the absence of clinical indications.³⁵ In line with these recommendations, the present meta-analysis provides quantitative evidence demonstrating that AVF ligation is associated with reductions in LVMI and cardiac index without compromising renal function, thereby supporting attenuation of the hyperdynamic cardiac state and informing patient selection and timing of closure.³⁵

From a clinical perspective, these findings support consideration of elective AVF ligation in selected patients with stable renal function and evidence of cardiovascular strain. Persistent AVFs may contribute to left ventricular hypertrophy and high-output heart failure, particularly in the setting of high-flow access.^3,18,32 Careful patient selection incorporating echocardiographic parameters, access flow assessment, and longitudinal renal function monitoring may help optimize therapeutic decision-making.^32–34

Future research should focus on long-term outcomes beyond structural improvement, including heart failure progression, arrhythmias, mortality, quality of life, and physical performance. Randomized trials with standardized eligibility criteria, consistent access flow measurements, and uniform follow-up intervals are needed to define optimal timing and patient selection for AVF ligation. Subgroup analyses may further clarify benefit in patients with high-flow fistulas or early cardiac dysfunction.

Limitations

Several limitations should be acknowledged. First, the number of randomized controlled trials was limited, and the overall evidence base included observational studies, which may be subject to residual confounding. Second, AVF flow volumes and biomarker assessment protocols were inconsistently reported, precluding flow-based or biomarker-specific subgroup analyses. Third, follow-up duration was relatively short in most studies, limiting assessment of long-term clinical outcomes. These limitations highlight the need for larger, prospective studies with standardized access flow measurements and longer follow-up.

Conclusion

In conclusion, this systematic review and meta-analysis demonstrates that arteriovenous fistula ligation is associated with reductions in LVMI and cardiac index, consistent with attenuation of the hyperdynamic cardiac state induced by a persistent fistula, without evidence of deterioration in renal function. While observational data predominate, concordant findings from randomized trials support the cardiovascular benefit of AVF closure in appropriately selected patients.

Supplemental Material

sj-docx-1-jva-10.1177_11297298261441029 – Supplemental material for A meta-analysis of the hemodynamic and echocardiographic changes following arteriovenous fistula ligation in chronic kidney disease patients

Supplemental material, sj-docx-1-jva-10.1177_11297298261441029 for A meta-analysis of the hemodynamic and echocardiographic changes following arteriovenous fistula ligation in chronic kidney disease patients by Mahmoud Einieh, Jose Matias Zaldumbide Diaz, Vitor Rezende, Mohammed Alam and Iuri Ferreira Felix in The Journal of Vascular Access

Footnotes

Abbreviations

AVF: arteriovenous fistula

CENTRAL: Cochrane central register of controlled trials

CO: cardiac output

ESKD: end-stage kidney disease

eGFR: estimated glomerular filtration rate

LAD: left atrial diameter

LVEF: left ventricular ejection fraction

LVEDDi: left ventricular end-diastolic diameter index

LVM: left ventricular mass

LVMI: left ventricular mass index

MD: mean difference

NT-proBNP: n-terminal pro-b-type natriuretic peptide

PRISMA: preferred reporting items for systematic reviews and meta-analyses

PROSPERO: international prospective register of systematic reviews

RCT: randomized controlled trial

RoB 2: Cochrane risk of bias tool version 2

ROBINS-I: risk of bias in non-randomized studies—of interventions

SVR: systemic vascular resistance

CMR: cardiac magnetic resonance

Author contributions

All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical approval

Ethical approval was not required for this systematic review and meta-analysis, as it utilized aggregated data from previously published studies and did not involve direct interaction with human participants or access to individual patient-level data.

ORCID iDs

Mahmoud Einieh

Jose Matias Zaldumbide Diaz

Vitor Rezende

Iuri Ferreira Felix

Supplemental material

Supplemental material for this article is available online.

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Supplementary Material

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