Rationale and Trial Design of MesEnchymal Stem Cell Trial in Preventing Venous Stenosis of Hemodialysis Vascular Access Arteriovenous Fistula (MEST AVF Trial)

Background: Hemodialysis arteriovenous fistulas (AVFs) are the preferred vascular access for patients on hemodialysis. In the Hemodialysis Fistula Maturation Study, 43.7% of the patients achieved unassisted maturation of their fistula without needing an intervention. Venous neointimal hyperplasia (VNH) and subsequent venous stenosis (VS) is responsible for lack of maturation. There are no therapies that can prevent VNH/VS formation. The goal of this paper is to present the background, rationale, and trial design of an innovative phase 1 / 2 clinical study that is investigating the safety of autologous adipose derived mesenchymal stem cells (AMSCs) delivered locally to the adventitia of newly created upper extremity radiocephalic (RCF) or brachiocephalic fistula (BCF). Methods: The rationale and pre-clinical studies used to obtain a physician sponsored investigational new drug trial (IND) are discussed. The trial design and endpoints are discussed. Results: This is ongoing trial which will complete this year. Conclusion: This is a phase 1 / 2 single center, randomized trial which will investigate safety and efficacy of autologous AMSCs in promoting maturation in new upper extremity AVFs.

Vein and artery diameter influence on arteriovenous fistula maturation and patency in a Mexican population

Background: There is no consensus of the optimal arterial and venous sizes on arteriovenous fistula (AVF) function and patency. The purpose of our study was to determine the influence of vein and artery sizes on maturation and patency in autologous first time AVF in a vascular access clinic of Mexican Social Security. Methods: Approved IRB single-center retrospective study in patients referred for their first AVF from 01/2018/ to 04/2020. Perianastomotic inner vein diameter and single inner artery diameter was recorded by duplex ultrasound. Outcomes were: failure to mature (FTM) and cumulative primary patency survival. Results: Eighty-six AVF’s were created (mean age 45.5 ± 15.1 years; 62.8% male; mean BMI 25.9 ± 4.3 kg/m2). About 86% were brachiocephalic AVF. Eight (8.1%) AVF had FTM. Mean follow-up was 19.7 ± 8.5 months. Two-year patency survival was 81.4%. FTM vein and artery diameters (2.1 ± 0.3 and 2.8 ± 0.7 mm respectively) were smaller than successful AVF’s (3.1 ± 0.9 and 3.5 ± 0.6 mm) ( p < 0.05). ROC curve calculated a 2.15 mm vein diameter cutoff (AUC: 0.86) and a 2.95 mm artery diameter cutoff (AUC: 079) for FTM AVF’s (83% sensitivity, 72% specificity both) ( p < 0.05). AVF’s created with a vein diameter <2.15 mm and <2.95 mm artery diameter had statistically significant lower patency survival than AVF’s with larger vein and artery diameters ( p < 0.05). Conclusion: Vein diameter <2.15 mm and artery diameter <2.95 mm influences AVF maturation and patency in a Mexican population.

Study on prediction of arterio-venous fistula maturation by flow mediated dilatation and AVF blood flow

Background: The physiology and pathology of AVF maturation depends on the vessels characteristics and its ability to remodel. Outcome of AVF using flow mediated dilatation (FMD), AVF blood flow and diameter has been studied. Methodology: Present observational study included single stage AVF (both Radiocephalic and Brachiocephalic) in consecutive CKD five patients ( n = 158) prospectively over 1 year. Demographic and Doppler ultrasound parameters of upper limb (for vessel diameter and FMD) at baseline were recorded. Blood flow, diameter and depth of AVF were studied at 2, 6 and 12 weeks and their association with clinical maturation (usage of fistula with two needles for 75% of dialysis sessions during 15 day period) was studied ( n = 129, after excluding lost to followup and expired patients; accordingly cohort was divided in matured ( M) or non-matured (NM) groups. Clinical and radiological parameters between both groups were compared; receiver operator curve (ROC) and correlation of Doppler parameters were analysed. Results: Of 129 AVF, 67.4% were matured and 32.5% non-matured. Mean age was 40 years with male predominance75% in both the groups. The mean arterial diameter for distal (NM = 1.96 ± 0.58 and M = 2.02 ± 0.41) and proximal AVF (NM = 3.37 ± 0.82 and M = 3.36 ± 0.75) was not statistically different in both the groups. The matured fistula group had a mean FMD of 11.67 ± 4.09 as against FMD value of 9.365 ± 3.55 in the failed fistula group ( p value 0.01). For maturation prediction, sensitivity and specificity of blood flow at 2 weeks were 86.2% and 59.5% and at 6 weeks 96.6% and 64.3%, respectively. In multivariate analysis predictors for AVF maturation were FMD (adjusted odds ratio (AOR) = 1.15) and blood flow (AOR = 1.67). Conclusion: Second and Sixth week AVF blood flow was found to be predicting AVF maturation. Higher baseline FMD correlated with the AVF maturation, but not with vessel diameter.

Role of Doppler ultrasonography in the evaluation of hemodialysis arteriovenous access maturation and influencing factors

The goal of vascular access creation is to achieve a functioning arteriovenous fistula (AVF) or arteriovenous graft (AVG). An autologous fistula has been shown to be superior to AVG or to central venous catheters (CVCs) with lowest rate of re-intervention, but vessel obstruction or immaturity accounts for 20 % to 54% of cases with primary failure of AVF. This review is focused on the factors influencing maturation; indication and timing of preoperative mapping/creation of vascular access; ultrasound parameters for creation AVF/AVG; early postoperative complications following creation of a vascular access; ultrasound determinants of fistula maturation and endovascular intervention in vascular access with maturation failure. However, vascular accesses that fail to develop, have a high incidence of correctable abnormalities, and these need to be promptly recognized by ultrasonography and managed effectively if a high success rate is to be expected. We review approaches to promoting fistula maturation and duplex ultrasonography (DUS) of evaluating vascular access maturation.