Arteriovenous Fistula Maturation in Hemodialysis Patients With or Without Positive Antiphospholipid Antibodies

Arteriovenous Fistula Maturation in Hemodialysis Patients With or Without Positive Antiphospholipid Antibodies : A Prospective Observational Cohort Study.

Hemodialysis (HD) is one of the most often used modalities of blood epuration in ends-stage renal diseases (ESRD) and requires the creation of a patent vascular access such as an arteriovenous fistula (AVF). Native AVF is associated with lower morbidity and mortality compared to hemocatheters.

AVF need a maturation process before its use. This process usually requires less than 6 weeks and consists in a complex vascular remodeling process. Maturation can be considered as the process leading to a newly created AVF being usable for hemodialysis; it encompasses enlargement and thickening of the draining fistula vein, increasing the blood flow in the absence of thrombosis and bleeding. According to the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, AVF is considered matured (and therefore usable for HD) if 6 weeks after AVF creation surgery: (a) its diameter is at least 6mm, (b) its depth less than 6mm, (c) flow rate is at least 600ml/min and (d) its length is at least 6cm in order to allow a two needles cannulation. Delayed AVF maturation is a major complication that affects more than half of the AVF. It can be defined as the delay or absence of maturation according to KDOQI guidelines. The pathophysiology of delay or absence of AVF maturation is complex and multifactorial. It mainly involves thrombosis, stenosis, endothelial dysfunction, and hypercoagulability states.

In order to promote AVF maturation, the 2019 ERA-EDTA Clinical practice guidelines on peri- and postoperative care of native AVF and grafts for HD in adults, propose some medical treatments.

Antiphospholipid syndrome (APS) is an autoimmune disease, characterized by a prothrombotic state affecting both arterial and venous vasculature. Classification criteria have been proposed in 2006. In HD patient, up to 37% of patients have persistent aPL positivity. aPL positivity has been associated with vascular access thrombosis in retrospective studies.

The investigators performed a retrospective analysis of 113 patients in the HD department of the Brugmann Hospital between 01/01/2019 and 01/08/2019. Unpublished data that are currently under evaluation for publication, showed that the prevalence of APS and antiphospholipid antibody positivity (aPL) without APS, was 18.5% and the prevalence of APS was 10.7%. Antiphospholipid antibody positivity was identified as a risk factor for delayed AVF maturation. In multivariate analysis, antiphospholipid antibody positivity and stenosis were both independent risk factors for delayed maturation. There is a statistically significant association between delayed native AVF maturation and antiphospholipid antibody positivity. This association was independent of arteriovenous stenosis. This data suggest a potential non-stenotic and/or non-thrombotic mechanism of aPL related delayed maturation of the AVF in HD patients. More interestingly, a significant association between aPL positivity (with or without antiphospholipid syndrome) and delayed AVF maturation was found. This association was independent of stenosis.

Considering this association between aPL and failure of native AVF maturation, the aim of the present study is to further evaluate this association in a prospective cohort and to further identify a potential treatment option in order to reduce the prevalence of this very common complication '(i.e. AVF delay or absence of maturation).

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases
• Intervention / Treatment: Other: Data collection in medical records; Other: Blood sampling

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Maxime Taghavi; Phone Number: 024752646; Email: Maxime.TAGHAVI@chu-brugmann.be

Study Locations

• Belgium
  • Brussels, Belgium, 1020
    • Recruiting
    • Brugmann University Hospital
    • Contact: Maxime Taghavi, MD PhD; Email: Maxime.TAGHAVI@chu-brugmann.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Incident patients with chronic kidney disease (CKD) on stage G3b to G5, not end-stage renal disease, according to KDIGO guidelines and aged from 18 to 75 years old.

Description

Inclusion Criteria:

Incident patients with chronic kidney disease (CKD) on stage G3b to G5, not end-stage renal disease, according to KDIGO guidelines

Exclusion Criteria:

• Patient already on hemodialysis maintenance therapy, or switching from peritoneal dialysis to hemodialysis
• Arteriovenous fistula creation not feasible surgically or technically, or surgery contra-indicated
• Known thrombophilia other than antiphospholipid syndrome
• Active neoplasia
• aPL assays not relevant (treatment, inflammatory state, etc...)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
APL negative; Patients without persistent antiphospholipid antibodies (aPL) positivity	Other: Data collection in medical records; Data collection in medical records; Other: Blood sampling; Blood plasma and serum collection for biobanking. Future laboratory analyses encompass the analysis of endothelial dysfunction markers and other markers implicated in APS.
APL positive; Patients with persistent antiphospholipid antibodies (aPL) positivity	Other: Data collection in medical records; Data collection in medical records; Other: Blood sampling; Blood plasma and serum collection for biobanking. Future laboratory analyses encompass the analysis of endothelial dysfunction markers and other markers implicated in APS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AVF maturation status	AVF maturation status according to KDIGO guidelines, evaluated by means of ultrasound/doppler (outflow, diameter, stenosis and/or thrombosis)	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional primary patency of AVF	Time between of AVF first use and AVF complication necessitating intervention	1 year
Type of AVF complication AVF Thrombosis	Identification of AVF complication: thrombosis/stenosis/bleeding complications/intimal hyperplasia dysfunction	1 year

Collaborators and Investigators

• Sponsor: Brugmann University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2024

Study Registration Dates

• First Submitted: October 27, 2023
• First Submitted That Met QC Criteria: October 27, 2023
• First Posted (Actual): November 2, 2023

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: October 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Disease Attributes; Congenital Abnormalities; Renal Insufficiency; Pathological Conditions, Anatomical; Cardiovascular Abnormalities; Vascular Malformations; Arteriovenous Malformations; Vascular Fistula; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Fistula; Arteriovenous Fistula
• Other Study ID Numbers: AVF Maturation-aPL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No