Acute Kidney Injury in Coronavirus Disease and Association with Thrombosis.

INTRODUCTION: Coronavirus disease (COVID-19) is a global pandemic which continues to cause systemic inflammation, leading to multi-system organ damage including acute kidney injury (AKI) and thrombotic complications. We hypothesize that D-dimer level predicts an increased risk of AKI and thrombotic complications in COVID-19. METHODS: This was a retrospective cohort study performed at a single-center academic center. Patients hospitalized with COVID-19 between January 1, 2020, and January 1, 2021, were included in the analysis. Demographics and associated medical records were reviewed from the electronic medical record. Statistical analysis was done to determine the incidence of AKI and thrombosis and if D-dimer was predictive of an adverse event. RESULTS: The study included 389 patients with the diagnosis of COVID-19 who were hospitalized. AKI was evident in 143 patients with 59 experiencing a thrombotic event. Factors associated with AKI included age, chronic kidney disease, proteinuria, use of outpatient angiotensin-blocking medications, and D-dimer greater than 1.75 (p < 0.05). Factors associated with thrombosis included use of outpatient anticoagulants, elevated WBC, interleukin-6 (IL-6), and D-dimer greater than 1.75 (p < 0.05). When D-dimer was dichotomized at the median value for the entire dataset (value greater than 1.75), there was good discrimination for AKI and very good discrimination for thrombosis. CONCLUSIONS: Complications of acute renal failure and thrombosis are common in patients presenting with COVID-19. D-dimer was found to be predictive of both. Future studies to validate the association of these two events in patients presenting with COVID-19 are warranted as early treatment with antithrombotic agents may have a role in preventing adverse sequelae and outcomes.

The FACT : Use of a novel intermittent pneumatic compression device to promote pre-surgery arm vein dilation in patients with chronic renal failure.

BACKGROUND: Arteriovenous fistula (AVF) creation and maturation for hemodialysis is globally a topic of importance given the poor results and high costs associated with renal care. Successful AVF (surgical or endovascular) creation requires appropriate superficial veins and quality arteries. Many procedures fail due to initial small veins with limited blood flow capacity and distensibility. Intermittent pneumatic compression has previously shown success in trials to increase superficial veins in patients with end stage renal disease post AVF. The objective of this study is to investigate the role of an intermittent pneumatic device, the Fist Assist®, to dilate cephalic arm veins in patients with advanced chronic kidney disease (CKD) prior to AVF placement. METHODS: Three centers enrolled subjects from June 2019 through July 2021. Baseline Doppler measurements of the cephalic vein in standard locations the forearm and upper arm with and without a blood pressure cuff were recorded. Patients were instructed and used Fist Assist® on their non-dominant arm for up to 4 h daily for 90 days. At approximately 3 months, Doppler measurements were repeated. The primary endpoint was cephalic vein enlargement with secondary endpoints based on percentage of veins approaching 2.5 mm in the forearm and 3.5 mm in the upper arm. RESULTS: Thirty-seven subjects with CKD (mean eGFR 13.8 mL/min) were enrolled and completed the trial. Paired-difference t-tests (one tail) for aggregate data showed significant venous dilation of the cephalic vein in both the forearm and upper arm after use with the Fist Assist® (p < 0.05). Mean differences in the forearm veins were approximately 0.6 and 1.1 mm in the upper arm cephalic vein after Fist Assist® application. There were no major complications reported by any subject during the trial. CONCLUSIONS: Fist Assist® use in patients with CKD is effective to enhance vein dilation. Forearm and upper arm cephalic veins increased on average 0.6 and 1.1 mm respectively after Fist Assist® application. This is the first trial to evaluate the effect of intermittent, focal pneumatic compression on pre-surgery vein diameter in patients with advanced CKD before AVF creation.

Creating patient-specific vein models to characterize wall shear stress in hemodialysis population.

End-Stage Renal Disease (ESRD) patients require arteriovenous fistulas (AVF) that allow a mature vein to withstand hemodialysis. Unfortunately, venous thrombosis and stenosis in the cephalic vein arch after AVF placement is common and heavily influenced by hemodynamics. To better assess forces and flow behavior in the cephalic arch, we have built patient-specific millifluidic models that allow us to explore the complex interplay between patient-specific vein geometry and fluctuating hemodynamics. These 3D models were created from patient-specific intravascular ultrasound and venogram images obtained three- and twelve-months post AVF creation and fabricated into soft elastomer-based millifluidic devices. Geometric validation of fabricated phantom millifluidic device shows successful replication of original computational 3D model. Millifluidic devices were perfused with a blood-mimicking fluid containing fluorescent tracer beads under steady-state physiologic cephalic vein flow conditions (20 mL/min). Particle image velocimetry was employed to calculate wall shear stress (WSS) across the cephalic arches. Experimental WSS profile evaluation reveals that the physiologic cephalic arch model yields WSS values within physiologic range [76-760 mPa]. Moreover, upon comparing WSS profiles across all models, it is noticeable that WSS values increase as vein diameter decreases, which further supports employed experimental and analysis strategy. The presented millifluidic devices show promise for experimental WSS characterization under pathologic flow conditions to contrast from calculated physiologic hemodynamics and better understand WSS influence on thrombosis and stenosis in hemodialysis patients.

Computational modeling of the cephalic arch predicts hemodynamic profiles in patients with brachiocephalic fistula access receiving hemodialysis.

BACKGROUND: The most common configuration for arteriovenous fistula is brachiocephalic which often develop cephalic arch stenosis leading to the need for numerous procedures to maintain access patency. The hemodynamics that contributes to the development of cephalic arch stenosis is incompletely understood given the inability to accurately determine shear stress in the cephalic arch. In the current investigation our aim was to determine pressure, velocity and wall shear stress profiles in the cephalic arch in 3D using computational modeling as tools to understand stenosis. METHODS: Five subjects with brachiocephalic fistula access had protocol labs, Doppler, venogram and intravascular ultrasound imaging performed at 3 and 12 months. 3D reconstructions of the cephalic arch were generated by combining intravascular ultrasounds and venograms. Standard finite element analysis software was used to simulate time dependent blood flow in the cephalic arch with velocity, pressure and wall shear stress profiles generated. RESULTS: Our models generated from imaging and flow measurements at 3 and 12 months offer snapshots of the patient's cephalic arch at a precise time point, although the remodeling of the vessel downstream of an arteriovenous fistula in patients undergoing regular dialysis is a dynamic process that persists over long periods of time (~ 5 years). The velocity and pressure increase at the cephalic bend cause abnormal hemodynamics most prominent along the inner wall of the terminal cephalic arch. The topology of the cephalic arch is highly variable between subjects and predictive of pathologic stenosis at later time points. CONCLUSIONS: Low flow velocity and wall pressure along the inner wall of the bend may provide possible nidus of endothelial activation that leads to stenosis and thrombosis. In addition, 3D modelling of the arch can indicate areas of stenosis that may be missed by venograms alone. Computational modeling reconstructed from 3D radiologic imaging and Doppler flow provides important insights into the hemodynamics of blood flow in arteriovenous fistula. This technique could be used in future studies to determine optimal flow to prevent endothelial damage for patients with arteriovenous fistula access.

A cohort study showing correspondence of low wall shear stress and cephalic arch stenosis in brachiocephalic arteriovenous fistula access.

BACKGROUND: A brachiocephalic fistula is frequently placed for hemodialysis; unfortunately, cephalic arch stenosis commonly develops, leading to failure. We hypothesized that a contribution to brachiocephalic fistula failure is low wall shear stress resulting in neointimal hyperplasia leading to venous stenosis. The objective of this investigation is to determine correspondence of low wall shear stress and the development of cephalic arch stenosis. METHODS: Forty subjects receiving hemodialysis with a primary brachiocephalic fistula access were followed from time of placement for 3 years or until cephalic arch stenosis. Venogram, Doppler, and viscosity were performed at time of fistula maturation, annually for 3 years or to time of cephalic arch stenosis. Computational hemodynamics modeling was performed to determine location and percent low wall shear stress in the arch. The relationship between wall shear stress at time of maturation and location of cephalic arch stenosis were estimated by correlating computational modeling and quadrant location of cephalic arch stenosis. RESULTS: In total, 32 subjects developed cephalic arch stenosis with 26 displaying correspondence between location of low wall shear stress at time of maturation and subsequent cephalic arch stenosis, whereas 6 subjects did not (p = 0.0015). Most subjects with correspondence had low wall shear stress areas evident in greater than 20% of the arch (p = 0.0006). Low wall shear stress was associated with a higher risk of cephalic arch stenosis in the 23-to-45 age group (p = 0.0029). CONCLUSIONS: The presence and magnitude of low wall shear stress in the cephalic arch is a factor associated with development of cephalic arch stenosis in patients with brachiocephalic fistula. Attenuation of low wall shear stress at time of maturation may help prevent the development of cephalic arch stenosis which is difficult to treat once it develops.

Outcomes After Percutaneous Angioplasty of Arteriovenous Fistulas and Grafts in African American Patients.

PURPOSE: Arteriovenous fistulas and grafts, necessary for hemodialysis, may develop stenoses due to neointimal hyperplasia, which often require percutaneous transluminal angioplasty. Patient and lesion characteristics were evaluated prior to angioplasty and were correlated with 1- and 6-month outcomes. MATERIALS AND METHODS: This was an observational study of African American hemodialysis patients who presented for angioplasty of a dysfunctional fistula or graft. Clinical outcomes were ascertained from dialysis facilities 1 month and 6 months after angioplasty. One-month clinical success was defined as dialyzer blood flows of 450 mL/min without complications or interval shunt thrombosis, interventions, or loss of access, which was rarely achieved at 6 months. Logistic regression models were used to evaluate associations of clinical variables with outcomes. RESULTS: There were 150 stenoses treated during 99 procedures performed on 82 patients. The clinical success rate at one month was 67% with no complications as a result of the percutaneous transluminal angioplasty. Success at 1 month was positively associated with use of aspirin (P = .005) and with referral for high venous pressures (P = .004). Six-month data were available for 81 procedures, with 45.7% requiring repeat angioplasty and 12.3% suffering major complications (thrombectomy, revision surgery, or access abandonment). Major complications were seen predominantly in patients who were not receiving aspirin. CONCLUSIONS: Aspirin use and high venous pressure were associated with 1-month clinical success and fewer major complications at 6 months. Future work should investigate biologic mechanisms of action of aspirin and long-term effects of use to maintain vascular access.

Use of Hepatitis C Positive Organs: Patient Attitudes in Urban Chicago.

BACKGROUND: Hepatitis C virus (HCV)-infected organs are being transplanted in patients with and without HCV in the direct-acting antiviral era. Little is known about patient attitudes towards receiving an HCV-positive organ. OBJECTIVES: The aim of this study is to determine transplant candidates' attitudes towards receiving HCV-positive organs. METHODS: Adult solid organ transplant candidates were identified during a clinic visit or during outpatient hemodialysis from May to December 2017. Willing participants completed a survey. Descriptive analysis including mean and median for continuous variables and frequencies for categorical variables were calculated by the appropriate statistical method and compared across willing, unsure, and unwilling patients and between willing and unsure/unwilling patients. RESULTS: Fifty patients were surveyed with median age 54.5 years (range 32-77). Eighty-eight percent were awaiting kidney transplant, and 12% were awaiting other organs. Median waitlist time was 39.8 months (range 1.7-203 months). Most patients (90%) had prior knowledge of HCV, but only 60% knew it was curable. Forty-six percent were willing, 30% were unsure, and 24% were unwilling to receive an HCV-positive organ. Those willing to accept an HCV-positive organ were significantly older, Caucasian, had shorter waitlist times, and had greater physician trust than those that were unsure/unwilling. Similar worries, such as HCV incurability, insurance coverage, fears over the organ not working, and post-transplant death, were expressed in both the willing and unsure/unwilling patients. CONCLUSIONS: The availability of HCV-positive organs may expand the donor pool and decrease waitlist times and mortality. These data highlight the need for patient education towards use of these organs.

Hemodynamic effects of hemodialyzer pump speed on arteriovenous fistulas
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AIM: Arteriovenous fistulas (AVF) are the optimal vascular access for hemodialysis although many fistulas fail. The impetus to increase hemodialyzer blood flow (QB) in order to maximize solute clearances may be counterbalanced if AVF suffer adverse hemodynamic effects from accelerated pump flows. The optimal QB to maintain adequate hemodialysis without potentially contributing to AVF dysfunction is unknown. The aim of this study was to measure the hemodynamic effects of increased QB on AVF. MATERIALS AND METHODS: A prospective cohort of 14 patients with primary brachiocephalic AVF underwent venous Doppler measurements prior to cannulation (QB0) and during hemodialysis with QB of 350 mL/min at a standardized anatomical location over 3 - 16 consecutive months. Measurements included vein diameter, blood flow velocity, and volumetric flow. RESULTS: 163 paired Doppler measurements (QB0 and QB350) were made in 14 subjects. There were no significant differences in venous diameter, but significant increases in blood flow velocity and volumetric flow (p < 0.001). Mean blood flow velocity increased from 86.6 ± 35.0 cm/s at QB0 to 105.7 ± 35.0 cm/s at QB350. Mean volumetric flow increased from 849 mL/min at QB0 to 1,059 mL/min at QB350. Vein diameters increased linearly over time, with no significant changes in blood velocity or volumetric flow, suggesting AVF maturation may improve tolerance of pumped blood flow. CONCLUSION: Blood flow velocity and volumetric flow increased when hemodialyzer blood pump was applied to an AVF, creating a situation in which increased turbulence and shear stress might be plausible. Further study is needed to determine if increased QB affects clinical outcomes of AVF.
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A Report of Two Cases of Hazards Associated with High Flow Arteriovenous Fistula in ESRD Patients.

High flow arteriovenous fistulas are a common clinical entity affecting patients with end-stage renal failure receiving hemodialysis. Given the difficulty in predicting who will develop a high flow arteriovenous fistula the exact prevalence is unclear. We present two cases of patients with high flow arteriovenous fistula that developed clinical cardiac failure at a time point after the fistula was placed with findings of significant cephalic arch stenosis. Both patients required treatment of cephalic arch stenosis with balloon angioplasty with subsequent surgical aneurism resection. Accurate and timely diagnosis of high flow arteriovenous hemodynamics by prospective monitoring of volumetric flow and cardiac function is required to halt this process prior to cardiac compromise.

Asymmetric Dimethylarginine does not Predict Early Access Events in Hemodialysis Patients with Brachiocephalic Fistula Access.

BACKGROUND: Vascular access for hemodialysis is best provided by an arteriovenous fistula (AVF). AVF fail primarily because of neointimal hyperplasia. Asymmetric dimethlyarginine (ADMA) is a naturally occurring analogue of L-arginine, which is elevated in renal failure and impairs endothelial cell function. ADMA inhibits nitric oxide synthetase, leading to impaired nitric oxide production and contributing to the development of neointimal hyperplasia. ADMA was measured at the time of AVF placement to evaluate associations with access failure. METHODS: ADMA was measured at the time of brachiocephalic access placement. Patients were followed for up to 12 months with end-points of access thrombosis or venous stenosis. RESULTS: Sixty patients with primary brachiocephalic fistulas were included in the study cohort. The median value for ADMA drawn at the time of AVF creation was 3.1 µmol/L. ADMA was not significantly associated with early thrombosis or venous stenosis events (P>0.05). CONCLUSION: Preoperative ADMA levels, as a surrogate for endothelial cell dysfunction and predictor of adverse access event (thrombosis or stenosis), were not associated with subsequent access events Future studies that identify markers of endothelial cell dysfunction are warranted.

A Predictive Framework to Elucidate Venous Stenosis: CFD & Shape Optimization.

The surgical creation of vascular accesses for renal failure patients provides an abnormally high flow rate conduit in the patient's upper arm vasculature that facilitates the hemodialysis treatment. These vascular accesses, however, are very often associated with complications that lead to access failure and thrombotic incidents, mainly due to excessive neointimal hyperplasia (NH) and subsequently stenosis. Development of a framework to monitor and predict the evolution of the venous system post access creation can greatly contribute to maintaining access patency. Computational fluid dynamics (CFD) has been exploited to inspect the non-homeostatic wall shear stress (WSS) distribution that is speculated to trigger NH in the patient cohort under investigation. Thereafter, CFD in liaison with a gradient-free shape optimization method has been employed to analyze the deformation modes of the venous system enduring non-physiological hemodynamics. It is observed that the optimally evolved shapes and their corresponding hemodynamics strive to restore the homeostatic state of the venous system to a normal, pre-surgery condition. It is concluded that a CFD-shape optimization coupling that seeks to regulate the WSS back to a well-defined physiological WSS target range can accurately predict the mode of patient-specific access failure.

Are Non-Newtonian Effects Important in Hemodynamic Simulations of Patients With Autogenous Fistula?

Given the current emphasis on accurate computational fluid dynamics (CFD) modeling of cardiovascular flows, which incorporates realistic blood vessel geometries and cardiac waveforms, it is necessary to revisit the conventional wisdom regarding the influences of non-Newtonian effects. In this study, patient-specific reconstructed 3D geometries, whole blood viscosity data, and venous pulses postdialysis access surgery are used as the basis for the hemodynamic simulations of renal failure patients with native fistula access. Rheological analysis of the viscometry data initially suggested that the correct choice of constitutive relations to capture the non-Newtonian behavior of blood is important because the end-stage renal disease (ESRD) patient cohort under observation experience drastic variations in hematocrit (Hct) levels and whole blood viscosity throughout the hemodialysis treatment. For this purpose, various constitutive relations have been tested and implemented in CFD practice, namely Quemada and Casson. Because of the specific interest in neointimal hyperplasia and the onset of stenosis in this study, particular attention is placed on differences in nonhomeostatic wall shear stress (WSS) as that drives the venous adaptation process that leads to venous geometric evolution over time in ESRD patients. Surprisingly, the CFD results exhibit no major differences in the flow field and general flow characteristics of a non-Newtonian simulation and a corresponding identical Newtonian counterpart. It is found that the vein's geometric features and the dialysis-induced flow rate have far greater influence on the WSS distribution within the numerical domain.

Increased Inlet Blood Flow Velocity Predicts Low Wall Shear Stress in the Cephalic Arch of Patients with Brachiocephalic Fistula Access.

BACKGROUND: An autogenous arteriovenous fistula is the optimal vascular access for hemodialysis. In the case of brachiocephalic fistula, cephalic arch stenosis commonly develops leading to access failure. We have hypothesized that a contribution to fistula failure is low wall shear stress resulting from post-fistula creation hemodynamic changes that occur in the cephalic arch. METHODS: Twenty-two subjects with advanced renal failure had brachiocephalic fistulae placed. The following procedures were performed at mapping (pre-operative) and at fistula maturation (8-32 weeks post-operative): venogram, Doppler to measure venous blood flow velocity, and whole blood viscosity. Geometric and computational modeling was performed to determine wall shear stress and other geometric parameters. The relationship between hemodynamic parameters and clinical findings was examined using univariate analysis and linear regression. RESULTS: The percent low wall shear stress was linearly related to the increase in blood flow velocity (p < 0.01). This relationship was more significant in non-diabetic patients (p < 0.01) than diabetic patients. The change in global measures of arch curvature and asymmetry also evolve with time to maturation (p < 0.05). CONCLUSIONS: The curvature and hemodynamic changes during fistula maturation increase the percentage of low wall shear stress regions within the cephalic arch. Low wall shear stress may contribute to subsequent neointimal hyperplasia and resultant cephalic arch stenosis. If this hypothesis remains tenable with further studies, ways of protecting the arch through control of blood flow velocity may need to be developed.

Hemodynamic and biologic determinates of arteriovenous fistula outcomes in renal failure patients.

The outcome of patients with end-stage renal disease on hemodialysis depends on a functioning vascular access. Although a variety of access options are available, the arteriovenous fistula remains the best vascular access. Unfortunately the success rate of mature fistula use remains poor. The creation of an arteriovenous fistula is followed by altered hemodynamic and biological changes that may result in neointimal hyperplasia and eventual venous stenosis. This review provides an overview of these changes and the needed research to provide a long lasting vascular access and hence improve outcomes for patients with end-stage renal disease.

Central venous catheters: incidence and predictive factors of venous thrombosis.

AIMS: Central venous catheter access in an acute setting can be a challenge given underlying disease and risk for venous thrombosis. Peripherally inserted central venous catheters (PICCs) are commonly placed but limit sites for fistula creation in patients with chronic renal failure (CKD). The aim of this study is to determine the incidence of venous thrombosis from small bore internal jugular (SBIJ) and PICC line placement. This investigation identifies populations of patients who may not be ideal candidates for a PICC and highlights the importance of peripheral vein preservation in patients with renal failure. MATERIALS AND METHODS: A venous Doppler ultrasound was performed at the time of SBIJ insertion and removal to evaluate for thrombosis in the internal jugular vein. Data was collected pre- and post-intervention to ascertain if increased vein preservation knowledge amongst the healthcare team led to less use of PICCs. Demographic factors were collected in the SBIJ and PICC groups and risk factor analysis was completed. RESULTS: 1,122 subjects had PICC placement and 23 had SBIJ placement. The incidence of thrombosis in the PICC group was 10%. One patient with an SBIJ had evidence of central vein thrombosis when the catheter was removed. Univariate and multivariate analysis demonstrated a history of transplant, and the indication of total parenteral nutrition was associated with thrombosis (p<0.001). The decrease in PICCs placed in patients with CKD 6 months before and after intervention was significant (p<0.05). CONCLUSIONS: There are subsets of patients ith high risk for thrombosis who may not be ideal candidates for a PICC.

Morphometric and histological parameters in veins of diabetic patients undergoing brachiocephalic fistula placement.

Diabetic patients with end-stage renal failure have higher rates of arteriovenous failures when compared with nondiabetics. The aim was to compare differences in indicators of vascular remodeling and endothelial dysfunction in veins of patients with or without diabetes at the time of surgical placement. In this prospective observational trial, vein samples were collected from patients when a brachiocephalic fistula was created. Morphometric measurements and extent of fibrosis were determined using Image J software. Histological analysis, for the presence of myofibroblasts and level of endothelial nitric oxide synthase, was performed by immunohistochemical staining and scored in semi-quantitative manner. Asymmetric dimethylarginine was determined at the time of access placement. Comparison of diabetics and nondiabetics was performed using Wilcoxon rank sum and Fisher's exact tests. Eighteen patients were included; 10 were diabetics. There was a significant difference in the measurement of vein area between groups, with diabetic vein samples having larger luminal area of average 832,001.18 µm(2) (317,582.17-3,695,670.36, P = 0.04). The maximal intimal to medial thickness ratio was higher in diabetic vein samples (0.71 vs. 0.24, P = 0.03) along with statistically significant higher maximal intimal thickness (312.12 vs. 115.14 µm, P = 0.03). There is a significant difference in vascular wall remodeling between diabetics and nondiabetics at the level of the cephalic vein at the time of brachiocephalic placement. The unexpected finding of significantly larger luminal area in diabetic veins could be a major factor positively affecting brachiocephalic outcomes in otherwise impaired remodeling in this patient population.