Temporal trends in hemodialysis access creation during the fistula first era.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

VasQ U.S. pivotal study demonstrates the safety and effectiveness of an external vascular support for arteriovenous fistula creation.

OBJECTIVE: Arteriovenous fistula (AVF) creation is a commonly performed vascular operation that reports 6-month functional success rates as low as 50%. Recently, a nitinol external vascular support device, VasQ, has shown potential in studies outside the United States (U.S.) to improve AVF outcomes when implanted at creation. Here, the pivotal study results of this novel technology in treating patients in the U.S. are described. METHODS: VasQ was implanted in 144 patients at 16 centers across the U.S. who were referred for creation of a new AVF and consented for enrollment in a 2-year, prospective, multicenter, single-arm, open-label study. Brachiocephalic (n = 129) and radiocephalic (n = 15) AVFs were analyzed. The primary endpoint was primary patency at 6 months compared against a performance goal of 55% derived from a systematic literature search. Safety endpoints included device-related events, ischemic steal, infection, aneurysm, and seroma at up to 6 months. Minimum arterial size was 2.0 mm; target veins were required to measure 2.5 to 6 mm. Key exclusion criteria were patients <18 or >80 years, those with known ipsilateral central venous occlusion, target cannulation zone venous depth greater than 8 mm, and New York Heart Association class 3 or 4. RESULTS: Patients were 61% male, 53% White, 35% African American, and 14% Hispanic. Mean age was 60 years, and median body mass index was 30.4. Of the patients, 69% were diabetic, 66% were on dialysis at the time of creation, and 70% had a prior access surgery. At 6 months, steal was observed in 2.1%, infection in 0.7%, and no aneurysms or seromas were seen. Primary patency at 6 months was 66% (P < .021 vs performance goal). Physiological maturation was achieved in 92.4% of patients. Successful two-needle cannulation for patients that entered the study on dialysis was achieved in 88% of VasQ AVFs at a median of 56 days. Pre-dialysis patients who initiated dialysis during the study achieved two-needle cannulation in 81.6% VasQ AVFs. Interventions were required at a rate of 1.07 per patient year over the entire study period. Two-year cumulative patency was 76.6% (95% confidence interval, 67.9%-83.4%) with no statistical difference between patients requiring interventions and those that did not. No patency differences were observed between brachiocephalic and radiocephalic AVFs. CONCLUSIONS: The U.S. pivotal study results demonstrated improved AVF outcomes and an excellent safety profile with VasQ use relative to traditional AVFs. Under the conditions of this trial, VasQ shows great promise in expeditiously and efficiently enhancing AVF functional success.

Evaluating national guideline concordance of recurrent interventions after radiocephalic arteriovenous fistula creation.

OBJECTIVE: Radiocephalic arteriovenous fistulas have been historically perceived as requiring multiple follow-up procedural interventions to achieve maturation and maintain patency. Recent clinical practice guidelines from the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) emphasize a patient-centered hemodialysis access strategy with new maximum targets for intervention rates, potentially conflicting with concomitant recommendations to prioritize autogenous forearm hemodialysis access creation. The present descriptive study seeks to assess whether radiocephalic fistulas can meet the KDOQI guideline benchmarks for interventions following access creation, and to elucidate clinical and anatomic characteristics associated with the timing and frequency of interventions following radiocephalic arteriovenous fistula creation. METHODS: Prospective patient-level data from the multicenter PATENCY-1 and PATENCY-2 randomized trials, which enrolled patients undergoing new radiocephalic arteriovenous fistula creation, was analyzed (ClinicalTrials.govNCT02110901 and NCT02414841). The primary outcome was the rate of interventions at 1 year postoperatively. Incidence rates were calculated, and time to surgical or endovascular intervention following fistula creation was modeled using recurrent event extensions of the Cox proportional hazards model. Confidence intervals at the 95% level were calculated using nonparametric bootstrapping. RESULTS: The cohort consisted of 914 patients; mean age was 57 years (standard deviation, 13 years), and 22% were female. Median follow-up was 707 days (interquartile range, 447-1066 days). The incidence of interventions per person-year was 1.04 (95% confidence interval [CI], 0.95-1.13) overall; 1.10 (95% CI, 0.98-1.21) before fistula use, and 0.96 (95% CI, 0.82-1.11) after fistula use. The most common interventions overall were balloon angioplasty (54.9% of all interventions), venous side-branch ligation (16.4%), and open revisions (eg, proximalization from snuffbox to wrist, 16.4%). The locations requiring balloon angioplasty included the juxta-anastomotic segment (51.7% of angioplasties), the outflow vein (29.2%), the inflow artery (14.8%), the central veins (3.8%), and the cephalic arch (0.5%). Common indications were to restore or maintain patency (75.6% of all interventions), assist maturation (14.9%), improve depth (4.4%), or improve augmentation (3.0%). In the multivariable regression analysis, female sex (adjusted hazard ratio [HR], 1.21; 95% CI, 1.05-1.45), diabetes (HR, 1.21; 95% CI, 1.01-1.46), and intraoperative vein diameter <3.0 mm (vs ≥4.0 mm: HR, 1.33; 95% CI, 1.02-1.66) were associated with earlier and more frequent interventions. Patients not on hemodialysis at the time of fistula creation underwent less frequent interventions (HR, 0.69; 95% CI, 0.59-0.81). CONCLUSIONS: Patients with radiocephalic arteriovenous fistulas can expect to undergo one intervention, on average, in the first year after creation, which aligns with current KDOQI guidelines. Patients already requiring hemodialysis, female patients, patients with diabetes, and patients with intraoperative vein diameters <3.0 mm were at increased risk for repeated intervention. No subgroup exceeded guideline-suggested maximum thresholds for recurrent interventions. Overall, the results demonstrate that creation of radiocephalic arteriovenous fistula remains a guideline-concordant strategy when part of an end-stage kidney disease life-plan in appropriately selected patients.

Staged autogenous to prosthetic hemodialysis access creation strategy to maximize forearm options.

OBJECTIVE: When an adequate cephalic vein is not available for fistula construction, surgeons often turn to basilic vein or prosthetic constructions. Single-stage forearm prosthetic hemodialysis accesses are associated with poor durability, and upper arm non-autogenous access options are often limited by axillary outflow failure, which inevitably drives transition to the contralateral arm or lower extremity. We hypothesized that initial creation of a modest flow proximal forearm arterial-venous anastomosis to dilate ("develop") inflow and outflow vessels, followed by a planned second-stage procedure to create a cannulation zone with a prosthetic graft in the forearm, would result in reliable and durable hemodialysis access in patients with limited options. METHODS: We performed an institutional cohort study from 2017 to 2021 using a prospectively maintained database supplemented with adjudicated chart review. Patients without traditional autogenous hemodialysis access options in the forearm underwent an initial non-wrist arterial-venous anastomosis creation in the forearm as a first stage, followed by a second-stage interposition graft sewn to the existing inflow and venous outflow segments to create a useable cannulation zone in the forearm while leveraging vascular development. Outcomes included time from second-stage access creation to loss of primary and secondary patency, frequency of subsequent interventions, and perioperative complications. RESULTS: The cohort included 23 patients; first-stage radial artery-based (74%) configurations were more common than brachial artery-based (26%). Mean age was 63 years (standard deviation, 14 years), and 65% were female. Median follow-up was 340 days (interquartile range [IQR], 169-701 days). Median time to cannulation from second-stage procedure was 28 days (IQR, 18-53 days). Primary, primary assisted, and secondary patency at 1 year was 16.7% (95% confidence interval [CI], 5.3%-45.8%), 34.6% (95% CI, 15.2%-66.2%), and 95.7% (95% CI, 81.3%-99.7%), respectively. Subsequent interventions occurred at a rate of 3.02 (IQR, 1.0-4.97) per person-year, with endovascular thrombectomy with or without angioplasty/stenting (70.9%) being the most common. There were no cases of steal syndrome. Infection occurred in two cases and were managed with antibiotics alone. CONCLUSIONS: For patients without adequate distal autogenous access options, staged prosthetic graft placement in the forearm offers few short-term complications and excellent durability with active surveillance while strategically preserving the upper arm for future constructions.

Achieving high maturation and cannulation rates of radial-cephalic arteriovenous fistulas with VasQ™ device.

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.

Contemporary outcomes of a "snuffbox first" hemodialysis access approach in the United States.

OBJECTIVE: The Society for Vascular Surgery guidelines for permanent hemodialysis (HD) access creation recommend prioritizing the most distal possible autogenous access to minimize complications and preserve more proximal options. The "snuffbox" arteriovenous fistula (AVF) is the most distal radial artery-cephalic vein AVF. Despite the theoretical benefits of the snuffbox approach, recent trends have been toward upper arm access. Our study sought to investigate the feasibility of a snuffbox-first strategy for HD access in all anatomically appropriate candidates. METHODS: From January 2016 to August 2019, all patients with end-stage renal disease (ESRD) or pre-ESRD under consideration for HD access were evaluated for a snuffbox-first approach by a team of vascular surgeons and nephrologists at a single, urban academic medical center in the United States. Data were collected prospectively and supplemented by medical record review. A survival analysis was performed to evaluate primary unassisted and secondary patency and clinical and functional maturation. Patients were censored if they had received a kidney transplant or had died. Cox proportional hazards regression was used to determine the risk factors for prolonged clinical maturation and functional maturation. RESULTS: A total of 55 snuffbox AVFs were created. The median patient age was 60 years (interquartile range [IQR], 52-70 years), and 52.7% of the patients were men. The median follow-up was 369 days (IQR, 166-509 days). The median survival for primary unassisted patency was 90 days (95% confidence interval [CI], 79-111). Secondary patency at 1 year was 92.3% (95% CI, 85.3%-99.9%). The clinical maturation rate at 1 year was 83.7% (n = 55; 95% CI, 66.8%-91.9%), and the functional maturation rate at 1 year was 85.6% (n = 40; 95% CI, 63.3%-94.4%). Of the patients who were pre-ESRD at AVF creation and had initiated HD during the study period, 87.5% had successfully received incident HD with their snuffbox AVF. Twenty-four patients were receiving HD via a catheter at snuffbox creation. Of those patients, the functional maturation rate at 1 year was 82.5% (95% CI, 44.8%-94.4%). The patients had undergone a median of two interventions (IQR, zero to seven interventions) in the first year. Of these, 46.9% were percutaneous angioplasty and 31.2% were side-branch ligation. Diabetes was associated with slower AVF clinical maturation (multivariate hazard ratio, 0.35; 95% CI, 0.15-0.82; P = .016). A larger artery diameter was associated with earlier AVF clinical maturation (multivariate hazard ratio, 6.64; 95% CI, 2.11-20.9). CONCLUSIONS: A snuffbox-first approach to HD access is a viable option for distal access creation in a cohort of patients requiring HD in the United States. Subsequent ancillary interventions to facilitate access maturation were required for most patients.

Postanesthesia ultrasound facilitates creation of more preferred accesses without affecting access survival.

OBJECTIVE: The results of preoperative ultrasound (pre-US) vein mapping for hemodialysis access creation can be affected by environmental and clinical factors, such as ambient temperature, acute illness, recent phlebotomy, and hypovolemia. These factors may inadvertently exclude otherwise viable veins as options for access creation. We hypothesized that repeating the ultrasound vein mapping immediately preoperatively after anesthesia administration (post-US) identifies additional veins not appreciated by pre-US, thereby altering the operative plan and producing more preferred accesses, particularly more forearm accesses. METHODS: We performed a retrospective cohort study of patients (N = 323) at one institution who underwent pre-US followed by creation of a permanent dialysis access (fistula or graft) between January 2008 and December 2013. By applying the Silva criteria to pre-US vein mapping reports, a preoperative surgical plan was established. There were 99 patients who underwent only pre-US (group I); an additional post-US was performed in 224 patients (group II). Using multivariable logistic regression, we tested the association of post-US (group II) with pre-US alone (group I) with a change in operative plan and placement of a more preferred access (ie, more distal and autogenous). We also analyzed access survival using multivariable Cox proportional hazards regression and determined maturation rates for accesses in groups I and II. RESULTS: In group II, there were more changes in operative plan after controlling for potential confounders (adjusted odds ratio, 1.96; 95% confidence interval, 1.18-3.25), and more preferred accesses were created (adjusted odds ratio, 1.82; 95% confidence interval, 1.01-3.27). In addition, more autogenous accesses were created in group II when initially only upper arm graft options had been identified (P = .01); overall, more forearm accesses were created in group II (P = .03). There was no significant difference in access maturation and patency in comparing accesses in group I and group II, despite creation of autogenous accesses in group II that are usually associated with higher rates of access failure. In fact, forearm radial-cephalic autogenous accesses created in group II had secondary patency rates of 91% at 2 years. CONCLUSIONS: Our study supports the hypothesis that the use of post-US in addition to pre-US leads to placement of more preferred accesses while maintaining maturation and patency rates. Ultrasound evaluation after anesthesia should be considered a step in the process of care for hemodialysis access creation to improve outcomes.

Improved outcomes with proximal radial-cephalic arteriovenous fistulas compared with brachial-cephalic arteriovenous fistulas.

BACKGROUND: Brachial-cephalic arteriovenous fistulas (BCFs) are associated with high-flow volumes, leading to potential risks such as arm swelling, steal syndrome, pseudoaneurysm (due to a pressurized access), and cephalic arch stenosis. We hypothesized that a proximal radial-cephalic fistula (prRCF) configuration mitigates these risks because a lower flow state is created. Furthermore, we also hypothesized that despite these lower flows, patencies (primary, primary assisted, secondary) are sustained. METHODS: Leveraging a prospectively collected database supplemented with detailed medical record data, analyses of patients undergoing BCF and prRCF were completed (November 2008 through March 2016). Preoperative clinical and imaging characteristics, operative variables, and postoperative complications were reviewed. The primary end point was a composite of arm swelling, steal, and pseudoaneurysm at 2 years. Fistulograms and interventions (surgical revision, thrombectomy, endovascular treatment of cephalic arch stenosis) censored at 2 years were compared between configurations. Patencies were plotted using Kaplan-Meier techniques and compared using Cox proportional hazards. RESULTS: During the study period, 345 arteriovenous fistulas and 72 prosthetic grafts were primarily placed; 56 patients underwent BCF and 50 patients underwent prRCF with a mean follow-up of 1.8 ± 1.7 (standard deviation) years. Except for prRCF patients being older, there was no difference between the groups with regard to preoperative characteristics. The artery diameter used for anastomosis was significantly larger in the BCF group (4.0 ± 1.1 mm vs 2.6 ± 0.8 mm; P < .001), with higher flow volumes at 6-week ultrasound examination (1060 ± 587 mL/min vs 735 ± 344 mL/min; P < .001). Complications (arm swelling, steal, pseudoaneurysm) were significantly more common in the BCF group (P = .02). There was a trend, albeit statistically insignificant, for the BCF group to require more cephalic arch stenosis interventions. Of those patients needing dialysis within 1 year, both BCF and prRCF were successfully used in the majority of patients (n = 27 [66%] vs n = 25 [63%]; P = 1.0). Unadjusted and adjusted primary, primary assisted, and secondary patency rates were similar between the groups. CONCLUSIONS: prRCFs have fewer complications yet similar midterm durability compared with BCFs. When it is anatomically feasible, prRCFs should be constructed over BCFs because of their superior physiology and clinical outcomes.

Cytosolic phospholipase A2α regulates G1 progression through modulating FOXO1 activity.

Group IVA phospholipase A2 [cytosolic phospholipase A2α (cPLA2α)] is a key mediator of inflammation and tumorigenesis. In this study, by using a combination of chemical inhibition and genetic approaches in zebrafish and murine cells, we identify a mechanism by which cPLA2α promotes cell proliferation. We identified 2 cpla2α genes in zebrafish, cpla2αa and cpla2αb, with conserved phospholipase activity. In zebrafish, loss of cpla2α expression or inhibition of cpla2α activity diminished G1 progression through the cell cycle. This phenotype was also seen in both mouse embryonic fibroblasts and mesangial cells. G1 progression was rescued by the addition of arachidonic acid or prostaglandin E2 (PGE2), indicating a phospholipase-dependent mechanism. We further show that PGE2, through PI3K/AKT activation, promoted Forkhead box protein O1 (FOXO1) phosphorylation and FOXO1 nuclear export. This led to up-regulation of cyclin D1 and down-regulation of p27(Kip1), thus promoting G1 progression. Finally, using pharmacologic inhibitors, we show that cPLA2α, rapidly accelerated fibrosarcoma (RAF)/MEK/ERK, and PI3K/AKT signaling pathways cooperatively regulate G1 progression in response to platelet-derived growth factor stimulation. In summary, these data indicate that cPLA2α, through its phospholipase activity, is a critical effector of G1 phase progression through the cell cycle and suggest that pharmacological targeting of this enzyme may have important therapeutic benefits in disease mechanisms that involve excessive cell proliferation, in particular, cancer and proliferative glomerulopathies.

Mammalian Target of Rapamycin Mediates Kidney Injury Molecule 1-Dependent Tubule Injury in a Surrogate Model.

Kidney injury molecule 1 (KIM-1), an epithelial phagocytic receptor, is markedly upregulated in the proximal tubule in various forms of acute and chronic kidney injury in humans and many other species. Whereas acute expression of KIM-1 has adaptive anti-inflammatory effects, chronic expression may be maladaptive in mice. Here, we characterized the zebrafish Kim family, consisting of Kim-1, Kim-3, and Kim-4. Kim-1 was markedly upregulated in kidney after gentamicin-induced injury and had conserved phagocytic activity in zebrafish. Both constitutive and tamoxifen-induced expression of Kim-1 in zebrafish kidney tubules resulted in loss of the tubule brush border, reduced GFR, pericardial edema, and increased mortality. Kim-1-induced kidney injury was associated with reduction of growth of adult fish. Kim-1 expression led to activation of the mammalian target of rapamycin (mTOR) pathway, and inhibition of this pathway with rapamycin increased survival. mTOR pathway inhibition in KIM-1-overexpressing transgenic mice also significantly ameliorated serum creatinine level, proteinuria, tubular injury, and kidney inflammation. In conclusion, persistent Kim-1 expression results in chronic kidney damage in zebrafish through a mechanism involving mTOR. This observation predicted the role of the mTOR pathway and the therapeutic efficacy of mTOR-targeted agents in KIM-1-mediated kidney injury and fibrosis in mice, demonstrating the utility of the Kim-1 renal tubule zebrafish models.

Biological grafts for hemodialysis access: historical lessons, state-of-the-art and future directions.

The vast majority of arteriovenous grafts (AVG) have been constructed using expanded polytetrafluoroethylene (ePTFE). While ePTFE grafts have the advantage of being relatively inexpensive and easy to manufacture, distribute, ship, and store, their primary patency rates are disappointing when compared with the native AVF. Though use of arteriovenous fistulas (AVF) in the United States has increased substantially, approximately 25% of hemodialysis patients continue to use AVG as their vascular access. We present here a comprehensive review of biological grafts and their use in hemodialysis vascular access. In this review, we discuss the use of synthetics and then explore the evolution of biological grafts over the past 20 years, their clinical impact, and future challenges in widespread clinical use in hemodialysis patients. Provided are in depth descriptions of currently used nonbiological arteriovenous grafts and the recent approaches in increasing the patency of synthetic grafts. Recent technological advances using tissue-engineered AVGs have shown promise for patients receiving hemodialysis and their potential to provide an attractive, viable option for vascular access have been discussed.

Cardiovascular implantable electronic device leads in CKD and ESRD patients: review and recommendations for practice.

Cardiovascular implantable electronic devices (CIEDs) are frequently utilized for management of cardiac dysrhythmias in patients with chronic kidney disease or end-stage renal disease receiving hemodialysis. The survival benefit from use of implantable cardioverter defibrillators in patients with CKD or ESRD is not as clear as in the general population, particularly when used for primary prevention of sudden cardiac death. Transvenous CIED leads are associated with central vein stenosis resulting in significant adverse consequences for existing or future arteriovenous access. Venous hypertension from CIED lead-related central vein stenosis is a challenging clinical problem and may require repeated percutaneous interventions, replacement of the CIED, or creation of alternative arteriovenous access. Infections associated with transvenous CIED leads are more frequent and associated with worse outcomes in patients with renal disease. Epicardial CIED leads or other nontransvenous devices may reduce complications of both central venous stenosis and endovascular infection in these vulnerable patients. Consensus recommendations are offered for avoidance and management of complications arising from the use of CIEDs and arteriovenous hemodialysis access.

Coupling growth-factor engineering with nanotechnology for therapeutic angiogenesis.

Therapeutic angiogenesis is an emerging paradigm for the management of ischemic pathologies. Proangiogenic Therapy is limited, however, by the current inability to deliver angiogenic factors in a sustained manner at the site of pathology. In this study, we investigated a unique nonglycosylated active fragment of hepatocyte growth factor/scatter factor, 1K1, which acts as a potent angiogenic agent in vitro and in a zebrafish embryo and a murine matrigel implant model. Furthermore, we demonstrate that nanoformulating 1K1 for sustained release temporally alters downstream signaling through the mitogen activated protein kinase pathway, and amplifies the angiogenic outcome. Merging protein engineering and nanotechnology offers exciting possibilities for the treatment of ischemic disease, and furthermore allows the selective targeting of downstream signaling pathways, which translates into discrete phenotypes.

Dialysis Access Considerations in Kidney Palliative Care.

In this review, we discuss common challenges at the interface between dialysis access planning, prognostication, and patient-centered decision making. Particularly for patients whose survival benefit from dialysis is attenuated by advanced age or other serious illness, knowing the potential complications and anticipated frequency of access procedures is essential for patients and families to be able to conceptualize what life on dialysis will look like. Although starting dialysis with a functioning graft or fistula is associated with reduced infection rates, mortality, hospitalizations, and cost compared with a central venous catheter, these benefits must be weighed against the chance that early access placement in an elderly or seriously ill patient is an unnecessary surgery because the chronic kidney disease never progresses, the patient dies before developing an indication to start dialysis, or, the patient prefers conservative kidney management over dialysis. Kidney palliative care is a growing subspecialty of nephrology focused on helping seriously ill patients navigate complex medical decisions, and may be useful for intensive goals-of-care discussions about treatment and access options for patients with limited anticipated survival because of age or other serious illness.

Contemporary outcomes of distal radial artery ligation for access related hand ischemia.

OBJECTIVES: Access related hand ischemia (ARHI) is a rare albeit morbid complication of hemodialysis access creation. Distal radial artery ligation (DRAL) has been described as a strategy to improve perfusion to the hand while maintaining the access. The objective of this study was to report longitudinal outcomes of DRAL for ARHI. METHODS: Retrospective cohort study (2015-2021) of all patients who underwent DRAL for ARHI at a tertiary care vascular center. Subjects were identified using the Mass General Brigham clinical data warehouse and data collection was supplemented with chart adjudication. Outcomes captured included 30-day complications and improvement in ARHI-related symptoms at 1 year. RESULTS: Thirty-one patients were included. Mean (SD) age was 59.9 (14.5) and 67.7% were male. Wrist radial-cephalic (74.2%) and proximal radial-cephalic (9.7%) configurations were most common. ARHI severity was: 9.7% stage 1 (retrograde flow without symptoms); 38.7% stage 2 (pain during exercise or dialysis); 41.9% stage 3 (pain at rest); and 9.7% stage 4 (tissue loss). High flow was present in 35.5% of patients at baseline with median (IQR) flow of 1670 ml/min (1478-1954). After DRAL, median (IQR) flow reduction in the high flow group was 953 ml/min (645-993); concurrent precision banding was performed in 29% to reduce flow. The 30-day risk of complication was 3.2% (n = 1 access thrombosis). During follow-up, 82.1% showed improvement in symptoms and 3.6% of patients needed an additional procedure for ARHI. Carpal tunnel surgery was required for improvement in 7.1% of patients and was suspected as the culprit of symptoms in 7.1%. CONCLUSION: Distal radial artery ligation for ARHI is safe and can improve ischemic symptoms in most patients while salvaging access function. Precision banding can serve as a useful adjunct in high flow accesses. Carpal tunnel syndrome should be considered as part of the differential diagnosis of hand pain in this population.

Comparative effectiveness of bovine carotid artery xenograft and polytetrafluoroethylene in hemodialysis access revision.

BACKGROUND: When hemodialysis arteriovenous accesses fail, autogenous options are often limited. Non-autogenous conduit choices include bovine carotid artery xenografts (BCAG) and expanded polytetrafluoroethylene (PTFE), yet their comparative effectiveness in hemodialysis access revision remains largely unknown. METHODS: A cohort study was performed from a prospectively collected institutional database from August 2010 to July 2021. All patients undergoing an arteriovenous access revision with either BCAG or PTFE were followed for up to 3 years from their index access revision. Revision was defined as graft placement to address a specific problem of an existing arteriovenous access while maintaining one or more of the key components of the original access (e.g. inflow, outflow, and cannulation zone). Outcomes were measured starting at the date of the index revision procedure. The primary outcome was loss of secondary patency at 3 years. Secondary outcomes included loss of post-intervention primary patency, rates of recurrent interventions, and 30-day complications. Pooled logistic regression was used to estimate inverse probability weighted marginal structural models for the time-to-event outcomes of interest. RESULTS: A total of 159 patients were included in the study, and 58% received access revision with BCAG. Common indications for revision included worn out cannulation zones (32%), thrombosis (18%), outflow augmentation (16%), and inflow augmentation (13%). Estimated risk of secondary patency loss at 3 years was lower in the BCAG group (8.6%, 3.9-15.1) compared to the PTFE group (24.8%, 12.4-38.7). Patients receiving BCAG experienced a 60% decreased relative risk of secondary patency loss at 3 years (risk ratio 0.40, 0.14-0.86). Recurrent interventions occurred at similar rates in the BCAG and PTFE groups, with 1.86 (1.31-2.43) and 1.60 (1.07-2.14) interventions at 1 year, respectively (hazard ratio 1.22, 0.74-1.96). CONCLUSIONS: Under the conditions of this contemporary cohort study, use of BCAG in upper extremity hemodialysis access revision decreased access abandonment when compared to PTFE.

Predicting recurrent interventions after radiocephalic arteriovenous fistula creation with machine learning and the PREDICT-AVF web app.

OBJECTIVE: Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines discourage ongoing access salvage attempts after two interventions prior to successful use or more than three interventions per year overall. The goal was to develop a tool for prediction of radiocephalic arteriovenous fistula (AVF) intervention requirements to help guide shared decision-making about access appropriateness. METHODS: Prospective cohort study of 914 adult patients in the United States and Canada undergoing radiocephalic AVF creation at one of the 39 centers participating in the PATENCY-1 or -2 trials. Clinical data, including demographics, comorbidities, access history, anatomic features, and post-operative ultrasound measurements at 4-6 and 12 weeks were used to predict recurrent interventions required at 1 year postoperatively. Cox proportional hazards, random survival forest, pooled logistic, and elastic net recurrent event survival prediction models were built using a combination of baseline characteristics and post-operative ultrasound measurements. A web application was created, which generates patient-specific predictions contextualized with the KDOQI guidelines. RESULTS: Patients underwent an estimated 1.04 (95% CI 0.94-1.13) interventions in the first year. Mean (SD) age was 57 (13) years; 22% were female. Radiocephalic AVFs were created at the snuffbox (2%), wrist (74%), or proximal forearm (24%). Using baseline characteristics, the random survival forest model performed best, with an area under the receiver operating characteristic curve (AUROC) of 0.75 (95% CI 0.67-0.82) at 1 year. The addition of ultrasound information to baseline characteristics did not substantially improve performance; however, Cox models using either 4-6- or 12-week post-operative ultrasound information alone had the best discrimination performance, with AUROCs of 0.77 (0.70-0.85) and 0.76 (0.70-0.83) at 1 year. The interactive web application is deployed at https://predict-avf.com. CONCLUSIONS: The PREDICT-AVF web application can guide patient counseling and guideline-concordant shared decision-making as part of a patient-centered end-stage kidney disease life plan.

ASDIN white paper: Management of cephalic arch stenosis endorsed by the American Society of Diagnostic and Interventional Nephrology.

Brachiocephalic arteriovenous fistulas (AVF) makeup approximately one third of prevalent dialysis vascular accesses. The most common cause of malfunction with this access is cephalic arch stenosis (CAS). The accepted requirement for treatment of a venous stenosis lesion is ⩾50% stenosis associated with hemodynamically abnormalities. However, the correlation between percentage stenosis and a clinically significant decrease in access blood flow (Qa) is low. The critical parameter is the absolute minimal luminal diameter (MLD) of the lesion. This is the parameter that exerts the key restrictive effect on Qa and results in hemodynamic and functional implications for the access. CAS is the result of low wall shear stress (WSS) resulting from the effects of increased blood flow and the unique anatomical configuration of the CAS. Decrease in WSS has a linear relationship to increased blood flow velocity and neointimal hyperplasia exhibits an inverse relationship with WSS. The result is a stenotic lesion. The presence of downstream venous stenosis causes an inflow-outflow mismatch resulting in increased pressure within the access. Qa in this situation may be decreased, increased, or within a normal range. Over time, the increased intraluminal pressure can result in marked aneurysmal changes within the AVF, difficulties with cannulation and the dialysis treatment, and ultimately, increasing risk of access thrombosis. Complete characterization of the lesion both hemodynamically and anatomically should be the first step in developing a strategy for management. This requires both access flow measurement and angiographic imaging. Patients with CAS present a relatively broad spectrum as relates to both of these parameters. These data should be used to determine whether primary treatment of CAS should be directed toward the anatomical lesion (small MLD and low Qa) or the pathophysiology (large MLD and high Qa).

Contemporary outcomes of precision banding for high flow hemodialysis access.

OBJECTIVE: High-flow hemodialysis accesses are a well-recognized source of patient morbidity. Among available management strategies inflow constriction based on real-time physiologic flow monitoring offers a technically straightforward data-driven approach with potentially low morbidity. Despite the benefits offered by this approach, large contemporary series are lacking. METHODS: A retrospective review of a prospectively maintained clinical database was undertaken to capture patients undergoing precision banding within a signal tertiary care institution between 2010 and 2019. Multivariable logistic regression modeling of thrombosis within 30 days and re-banding within 1 year were performed. RESULTS: In total, 297 patients underwent banding during the study period for a total number of 398 encounters. Median [IQR] follow-up was 157 [52-373] days. Most accesses were upper arm with brachial artery inflow (84%) and half of the banding procedures were performed for flow imbalance based on exam, duplex, or fistulogram. Median flow rate reduction was 58%. The 30-day thrombosis rate after banding was 15 of 397 (3.8%) with a median time to event of 5.5 days (2-102). The re-banding rate within a year was 54 of 398 (14%) with a median time to re-banding of 134 days [56-224]. Multivariate logistic regression analysis using a univariate screen did not identify any predictors of 30-day thrombosis. Having a forearm radial-cephalic AVF compared to all other access types was protective against need for rebanding at 1 year (OR 0.12 95% CI 0.02-0.92, p = 0.04), as was flow imbalance as the indication for banding (OR 0.43 95% 0.23-0.79, p = 0.006). CONCLUSIONS: Precision banding offers an effective, low-morbidity approach for high-flow hemodialysis accesses. Early thrombosis is a rare event after precision banding, although in the long term, one in four patients will require re-banding to maintain control of flow volumes.

APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome.

Error-free chromosome segregation depends on timely activation of the multi-subunit E3 ubiquitin ligase APC/C. Activation of the APC/C initiates chromosome segregation and mitotic exit by targeting critical cell-cycle regulators for destruction. The APC/C is the principle target of the mitotic checkpoint, which prevents segregation while chromosomes are unattached to spindle microtubules. We now report the identification and characterization of APC16, a conserved subunit of the APC/C. APC16 was found in association with tandem-affinity-purified mitotic checkpoint complex protein complexes. APC16 is a bona fide subunit of human APC/C: it is present in APC/C complexes throughout the cell cycle, the phenotype of APC16-depleted cells copies depletion of other APC/C subunits, and APC16 is important for APC/C activity towards mitotic substrates. APC16 sequence homologues can be identified in metazoans, but not fungi, by four conserved primary sequence stretches. We provide evidence that the C. elegans gene K10D2.4 and the D. rerio gene zgc:110659 are functional equivalents of human APC16. Our findings show that APC/C is composed of previously undescribed subunits, and raise the question of why metazoan APC/C is molecularly different from unicellular APC/C.