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Background: Hemodialysis is the predominant treatment modality for chronic kidney disease, with arteriovenous fistula (AVF) being considered to be the preferred type of long‐term vascular access. Implantation of the external anastomotic VasQ™ support device during AVF creation has been suggested to improve the functional outcomes of AVFs. In the current study, we report the clinical outcomes when using the device with radial‐cephalic AVF (RCAVF) creation in a large cohort over 3 years. Methods: One hundred fifty RCAVFs were created between June 2018 and August 2021 with implantation of VasQ™. Time to maturation, cannulation characteristics, and assisted (AP) and secondary patency (SP) rates were analyzed. Results: In this predominantly male (68%), median 64 years old cohort, 150 VasQ™ devices were implanted. Physiological maturation was achieved in 142/150 (95%) and was unassisted in 133/150 (89%). Of those, 129 matured within 1 month and four additional AVFs within 165 days. Eight AVFs achieved maturation following percutaneous transluminal angioplasty, and one required surgical patch angioplasty. The median time from creation to first successful cannulation in dialysis patients was 41 days. AP at 6, 12, 18, 24, and 30 months was 89%, 81%, 78%, 73%, and 73%, and SP was 94%, 87%, 86%, 84%, and 84%, respectively. Conclusions: Consistent use of the VasQ™ device in RCAVF creation demonstrates excellent AVF maturation and patency rates with very low frequency of assisted maturation and interventions for maintenance. The VasQ™ device appears a suitable aid in increasing the creation of functional RCAVFs. [ABSTRACT FROM AUTHOR]

Gene array-type experiments have identified large numbers of genes thought to be important for the integrity of the glomerular slit diaphragm. Confirmation of individual proteins has been limited by the expenses and time involved in generating transgenic or knockout mice for each candidate. We present a functional screening assay based on the clearance of a 70-kDa fluorescent dextran in another vertebrate system that is rapid and low in cost. In the pronephric glomerulus of larval zebrafish, we have demonstrated quantifiable loss of slit diaphragm integrity in a zebrafish model of puromycin aminonucleoside (PA) toxicity. In addition, after knockdown of CD2-associated protein (CD2AP) and podocin, two well-characterized genetic contributors to podocyte differentiation in mammals, we observed glomerular loss of serum macromolecules similar to that seen in mammalian kidneys with inborn mutations in these genes. Increased filtration of 70-kDa FITC-labeled dextran correlates with effacement of podocyte foot processes in ultrastructural analysis. These findings document the value of the zebrafish model in genomics and pharmacological screening applications. podocyte; nephrotic syndrome; puromycin aminonucleoside; CD2-associated protein; podocin

Acute renal failure (ARF) is characterized by a very high mortality essentially unchanged over the past 40 years. Simple vertebrate models are needed to improve our understanding of ARF and facilitate the development of novel therapies for this clinical syndrome. Here, we demonstrate that gentamicin, a commonly used nephrotoxic antibiotic, causes larval zebrafish to develop ARF characterized by histological and functional changes that mirror aminoglycoside toxicity in higher vertebrates and inability of zebrafish to maintain fluid homeostasis. We developed a novel method to quantitate renal function in larval zebrafish and demonstrate a decline in glomerular filtration rate after gentamicin exposure. The antineoplastic drug cisplatin, whose use in humans is limited by kidney toxicity, also causes typical histological changes and a decline in renal function in larval zebrafish. A specific inhibitor of Omi/HtrA2, a serine protease implicated in cisplatin-induced apoptosis, prevented renal failure and increased survival. This protective effect was confirmed in a mouse model of cisplatin-induced nephrotoxicity. Therefore, zebrafish provides a unique model system, amenable to genetic manipulation and drug screening, to explore the pathophysiology of ARE and establish novel therapies with potential use in mammals. animal model; drug development; glomerular filtration; fluorescence

Although forearm arteriovenous fistulas (AVFs) are the preferred initial vascular access for hemodialysis based on national guidelines, there are no population-level studies evaluating trends in creation of forearm vs upper arm AVFs and arteriovenous grafts (AVGs). The purpose of this study was to report temporal trends in first-time permanent hemodialysis access type, and to assess the effect of national initiatives on rates of AVF placement. Retrospective cross-sectional study (2012-2022) utilizing the Vascular Quality Initiative database. All patients older than 18 years with creation of first-time upper extremity surgical hemodialysis access were included. Anatomic location of the AVF or AVG (forearm vs upper arm) was defined based on inflow artery, outflow vein, and presumed cannulation zone. Primary analysis examined temporal trends in rates of forearm vs upper arm AVFs and AVGs using time series analyses (modified Mann-Kendall test). Subgroup analyses examined rates of access configuration stratified by age, sex, race, dialysis, and socioeconomic status. Interrupted time series analysis was performed to assess the effect of the 2015 Fistula First Catheter Last initiative on rates of AVFs. Of the 52,170 accesses, 57.9% were upper arm AVFs, 25.2% were forearm AVFs, 15.4% were upper arm AVGs, and 1.5% were forearm AVGs. From 2012 to 2022, there was no significant change in overall rates of forearm or upper arm AVFs. There was a numerical increase in upper arm AVGs (13.9 to 18.2 per 100; P =.09), whereas forearm AVGs significantly declined (1.8 to 0.7 per 100; P =.02). In subgroup analyses, we observed a decrease in forearm AVFs among men (33.1 to 28.7 per 100; P =.04) and disadvantaged (Area Deprivation Index percentile ≥50) patients (29.0 to 20.7 per 100; P =.04), whereas female (17.2 to 23.1 per 100; P =.03), Black (15.6 to 24.5 per 100; P <.01), elderly (age ≥80 years) (18.7 to 32.5 per 100; P <.01), and disadvantaged (13.6 to 20.5 per 100; P <.01) patients had a significant increase in upper arm AVGs. The Fistula First Catheter Last initiative had no effect on the rate of AVF placement (83.2 to 83.7 per 100; P =.37). Despite national initiatives to promote autogenous vascular access, the rates of first-time AVFs have remained relatively constant, with forearm AVFs only representing one-quarter of all permanent surgical accesses. Furthermore, elderly, Black, female, and disadvantaged patients saw an increase in upper arm AVGs. Further efforts to elucidate factors associated with forearm AVF placement, as well as potential physician, center, and regional variation is warranted. [ABSTRACT FROM AUTHOR]