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BackgroundPatients receiving maintenance dialysis represent a high risk, immune-compromised population with 15-25% COVID mortality rate who were unrepresented in clinical trials evaluated for mRNA vaccines’ emergency use authorization.MethodAll patients receiving maintenance dialysis that received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021 were included. We report seroresponse based on levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen (seropositive ≥2) using FDA-approved semi-quantitative chemiluminescent assay (ADVIA Centaur® XP/XPT COV2G).ResultsAmong 186 dialysis patients from 32 clinics in 8 states tested 23±8 days after receiving 2 vaccine doses, mean age was 68±12 years, with 47% women, 21% Black, 26% residents in long-term care facilities and 97% undergoing in-center hemodialysis. Overall seropositive rate was 165/186 (88.7%) with 70% at maximum titer and with no significant difference in seropositivity between BNT162b2/Pfizer (N=148) and mRNA-1273/Moderna (N=18) vaccines (88.1% vs. 94.4%, p=0.42). Among patients with COVID-19 history, seropositive rate was 38/38 (100%) with 97% at maximum titer.ConclusionMost patients receiving maintenance dialysis were seropositive after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. Early evidence suggests that vaccinated dialysis patients with prior COVID-19 develop robust antibody response. These results support an equitable and aggressive vaccination strategy for eligible dialysis patients, regardless of age, sex, race, ethnicity, or disability, to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.SignificanceIn this retrospective observational evaluation of SARS-CoV-2 mRNA vaccine response defined by detectable levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen of ≥2 in serum of patients receiving maintenance dialysis, 165/186 (88.7%) were found to be seropositive (with 70% at maximum titer) at least 14 days after completing the second dose. No significant differences were observed by race or other subgroup or by vaccine manufacturer. Therefore, an equitable and aggressive vaccination strategy for all eligible maintenance dialysis patients, regardless of age, sex, race, ethnicity, or disability, is warranted to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.

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).

The development of venous intimal hyperplasia (IH) has been historically associated with failure of arteriovenous fistulas (AVF) used for hemodialysis. This long-standing assumption, based on histological observations, has been recently challenged by clinical studies indicating that the size of the intima by itself is not enough to explain stenosis or AVF maturation failure. Irrespective of this lack of association, IH is present in most native veins and fistulas, is prominent in many cases, and suggests a role in the vein that may not be reflected by its dimensions. Therefore, the contribution of IH to AVF dysfunction remains controversial. Using only clinical data and avoiding extrapolations from animal models, we critically discuss the biological significance of IH in vein remodeling, vascular access function, and the response of the venous wall to repeated trauma in hemodialysis patients. We address questions and pose new ones such as: What are the factors that contribute to IH in pre-access veins and AVFs? Do cellular phenotypes and composition of the intima influence AVF function? Are there protective roles of the venous intima? This review explores these possibilities, with hopes of rekindling a critical discussion about venous IH that goes beyond thickness and AVF outcomes.

The ideal blood pressure (BP) target for renoprotection is uncertain in patients with non-diabetic chronic kidney disease (CKD), especially considering the influence exerted by pre-existing proteinuria. In this pooled analysis of landmark trials, we coalesced individual data from 5001 such subjects randomized to intensive versus standard BP targets. We employed multivariable regression to evaluate the relationship between follow-up systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CKD progression (defined as glomerular filtration rate decline by 50% or end-stage renal disease), focusing on the potential for effect modification by baseline proteinuria or albuminuria. The median follow-up was 3.2 years. We found that SBP rather than DBP was the primary predictor of renal outcomes. The optimal SBP target was 110-129 mm Hg. We observed a strong interaction between SBP and proteinuria such that lower SBP ranges were significantly linked with progressively lower CKD risk in grade A3 albuminuria or ≥0.5-1 g/day proteinuria (relative to SBP 110-119 mm Hg, the adjusted HR for SBP 120-129 mm Hg, 130-139 mm Hg, and 140-149 mm Hg was 1.5, 2.3, and 3.3, respectively; all p0.05), while in grade A1 albuminuria or proteinuria 0.1). We conclude that in non-diabetic CKD, stricter BP targets

Neointimal cells are an elusive population with ambiguous origins, functions, and states of differentiation. Expansion of the venous intima in arteriovenous fistula (AVF) is one of the most prominent remodeling processes in the wall after access creation. However, most of the current knowledge about neointimal cells in AVFs comes from extrapolations from the arterial neointima in non-AVF systems. Understanding the origin of neointimal cells in fistulas may have important implications for the design and effective delivery of therapies aimed to decrease intimal hyperplasia (IH). In addition, a broader knowledge of cellular dynamics during postoperative remodeling of the AVF may help clarify other transformation processes in the wall that combined with IH determine the successful remodeling or failure of the access. In this review, we discuss the possible anatomical sources of neointimal cells in AVFs and their relative contribution to intimal expansion.

BACKGROUND: The role of hyaluronan (HA) in the development and progression of diabetic kidney disease (DKD), as well as the precise mechanisms and consequences of HA involvement in this pathology are still to be clarified. METHODS: In this study, we assayed the effects of the HA synthesis inhibitor 4-methylumbelliferone (4-MU) on the development of DKD. Diabetic type 2 model mice (eNOS(−/−) C57BLKS/J(db)) were fed artificial diets containing 5% 4-MU or not for 9 weeks. Plasma glucose, glomerular filtration rate (GFR), albumin to creatinine ratio (ACR), and biomarkers of kidney function and systemic inflammation were measured at baseline and after treatment. Diabetic nephropathy was further characterized in treated and control mice by histopathology. RESULTS: Treated animals consumed a daily dose of approximately 6.2 g of 4-MU per kg of body weight. At the end of the experimental period, the 4-MU supplemented diet resulted in a significant decrease in non-fasting plasma glucose (516 [interquartile range 378–1170] vs. 1149 [875.8–1287] mg/dL, P=0.050) and a trend toward lower HA kidney content (5.6 ± 1.5 vs. 8.8 ± 3.1 ng/mg of kidney weight, P=0.070) compared to the control diet, respectively. Diabetic animals treated with 4-MU showed significantly higher GFR and lower urine ACR and plasma cystatin C levels than diabetic controls. Independent histological assessment of DKD also demonstrated a significant decrease in mesangial expansion score and glomerular injury index in 4-MU-treated mice compared to controls. Plasma glucose showed a strong correlation with kidney HA levels (r=0.66, P=0.0098). Both total hyaluronan (r=0.76, P=0.0071) and low-molecular-weight hyaluronan content (r=0.64, P=0.036) in the kidneys correlated with urine ACR in mice. CONCLUSION: These results show that the hyaluronan synthesis inhibitor 4-MU effectively slowed the progression of DKD and constitutes a potential new therapeutic approach to treat DKD.

Hand ischemia is a relatively common complication of hemodialysis arteriovenous (AV) access. Clinical manifestations frequently start with pale and cold ipsilateral hand. Symptoms can progress to pain during dialysis and can eventually lead to tissue necrosis and gangrene if not addressed in a timely fashion. Comprehensive physical examination of the hand, AV access, and comparing it with the contralateral hand will assist in differentiating hand ischemia from carpal tunnel syndrome, osteoarthritis of the hand, and others. There are several treatment options for hand ischemia based on the severity of symptoms. Conservative management with careful monitoring can be applied in early stages. However, if symptoms persist or worsen, a full arteriogram of the ipsilateral extremity should be performed to evaluate for the presence of arterial stenosis. Angioplasty of the arterial stenosis, if present, will frequently lead to the resolution of symptoms. There are several percutaneous and surgical treatment options for hand ischemia, if no arterial stenosis was found or angioplasty does not relieve symptoms. We discuss in this article these treatment options in detail. Treatment goal is to improve hand ischemia symptoms while maintaining hemodialysis AV access and preserving patient's hand. Access ligation remains a treatment of last resort.

Background and ObjectivesWhile most maintenance dialysis patients exhibit initial seroresponse to vaccination, concerns remain regarding the durability of this antibody response. This study evaluated immunity over time.Design, setting, participants, and measurementsThis retrospective cohort study included maintenance dialysis patients from a midsize national dialysis provider who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. Immunoglobulin G spike antibodies (SAb-IgG) titers were assessed monthly with routine labs beginning after full vaccination and followed over time; the semiquantitative SAb-IgG titer reported a range between 0 and ≥ 20 U/L. Descriptive analyses compared trends over time by prior history of COVID-19 and type of vaccine received. Time-to-event analyses were conducted for the outcome of loss of seroresponse (SAb-IgG < 1 U/L or development of COVID-19). Cox proportional hazards regression was used to adjust for additional clinical characteristics of interest.ResultsAmong 1898 maintenance dialysis patients, 1567 (84%) had no prior history of COVID-19. Patients without a history of COVID-19 had declining titers over time. Among 441 BNT162b2/Pfizer recipients, median [IQR] SAb-IgG titer declined from 20 [5.99-20] U/L in month 1 to 1.30 [0.15-3.59] U/L by month 6. Among 779 mRNA-1273/Moderna recipients, median [IQR] SAb-IgG titer declined from 20 [20-20] in month 1 to 6.20 [1.74-20] by month 6. The 347 Ad26.COV2.S/Janssen recipients had a lower titer response than mRNA vaccine recipients over all time periods. In time-to-event analyses, Ad26.COV2.S/Janssen and mRNA-1273/Moderna recipients had the shortest and longest time to loss of seroresponse, respectively. The maximum titer reached in the first two months after full vaccination was predictive of the durability of the SAb-IgG seroresponse; patients with SAb-IgG titer 1-19.99 U/L were more likely to have loss of seroresponse compared to patients with SAb-IgG titer ≥ 20 U/L (HR 23.9 [95% CI: 16.1-35.5]).ConclusionsVaccine-induced seroresponse wanes over time among maintenance dialysis patients across vaccine types. Early titers after full vaccination predict the durability of seroresponse.

BACKGROUND AND OBJECTIVES: Although most patients receiving maintenance dialysis exhibit initial seroresponse to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, concerns exist regarding the durability of this antibody response. This study evaluated seroresponse over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included patients on maintenance dialysis, from a midsize national dialysis provider, who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. IgG spike antibodies (anti-spike IgG) titers were assessed monthly with routine laboratory tests after vaccination; the semiquantitative assay reported a range between zero and ≥20 Index. Descriptive analyses compared trends over time by history of coronavirus disease 2019 (COVID-19) and vaccine type. Time-to-event analyses examined the outcome of loss of seroresponse (anti-spike IgG

ImportanceVaccines against SARS-CoV-2 are highly effective in the general population; however, their efficacy may be diminished in maintenance dialysis patients, a population particularly vulnerable to COVID-19 infection and morbidity.ObjectiveWe assessed vaccine response in a national sample of maintenance dialysis patients and identified predictors of response.DesignRetrospective cohort studySetting130 Dialysis Clinic, Inc (DCI) facilitiesParticipantsMaintenance dialysis patients without known prior COVID-19 or a positive baseline antibody titerExposure(s)Vaccine type and clinical characteristicsMain Outcome(s)Using a semi-quantitative assay for antibodies against SARS-CoV-2 spike antigen, vaccine response was defined as at least one titer ≥1 U/L between 14 and 74 days after completion of a SARS-CoV-2 vaccine series. Regression analysis was used to identify characteristics associated with response.ResultsAmong 1528 patients, 437 received BNT162b2/Pfizer vaccine, 766 received mRNA-1273/Moderna, and 325 received Ad26.COV2.S/Janssen. Serologic response differed significantly by vaccine type: 381/437 (87%) among BNT162b2/Pfizer recipients, 736/766 (96%) among mRNA-1273/Moderna recipients, and 119/325 (37%) among Ad26.COV2.S/Janssen recipients. Vaccine type, older age, immune-modulating medication, history of transplantation, and lower serum albumin were associated with vaccine non-response.Conclusions and RelevanceSerologic response to mRNA vaccines is robust among maintenance dialysis patients. Future research should evaluate durability of this response, correlation between seroresponse and protection from COVID-19, and the role of the AD26.COV2.S/Janssen vaccine in this vulnerable population.

Background and objectives:The venous vasa vasorum is the mesh of microvessels that provide oxygen and nutrients to the walls of large veins. Whether changes to the vasa vasorum have any effects on human arteriovenous fistula outcomes remains undetermined. In this study, we challenged the hypothesis that inadequate vascularization of the arteriovenous fistula wall is associated with maturation failure.Design, setting, participants, and measurements:This case–control pilot study includes pre-access veins and arteriovenous fistula venous samples (i.e. tissue pairs) from 30 patients undergoing two-stage arteriovenous fistula creation (15 matured and 15 failed to mature). Using anti-CD31 immunohistochemistry, we quantified vasa vasorum density and luminal area (vasa vasorum area) in the intima, media, and adventitia of pre-access veins and fistulas. We evaluated the association of pre-existing and postoperative arteriovenous fistula vascularization with maturation failure and with postoperative morphometry.Results:Vascularization of veins and arteriovenous fistulas was predominantly observed in the outer media and adventitia. Only the size of the microvasculature (vasa vasorum area), but not the number of vessels (vasa vasorum density), increased after arteriovenous fistula creation in the adventitia (median vasa vasorum area 1366 µm2/mm2(interquartile range 495–2582) in veins versus 3077 µm2/mm2(1812–5323) in arteriovenous fistulas, p Conclusion:The lack of change in intimal and medial vascularization after arteriovenous fistula creation argues against higher oxygen demand in the inner walls of the fistula during the vein to arteriovenous fistula transformation. Postoperative intimal hyperplasia in the arteriovenous fistula wall appears to thrive under hypoxic conditions. Vasa vasorum density and area by themselves are not predictive of maturation outcomes.

Purpose: Over 468,000 patients in the United States use hemodialysis to manage End Stage Renal Disease (ESRD). The purpose of this study was to determine whether the dialysis access Clinical Performance Measures (CPMs) of Centers for Medicare & Medicaid Services (CMS) ESRD Quality Incentive Program (QIP) have increased arteriovenous fistula (AVF) rates and decreased long-term tunneled hemodialysis catheter (TDC) rates among hemodialysis patients in United States. Methods: Retrospective observational study: evaluated reported AVF and long-term TDC rates of 4804 dialysis facilities which reported dialysis access data as part of the ESRD QIP from Payment Year (PY) 2014–2020. Facilities were also sorted by specific additional criteria to examine disparities in dialysis access. Results: Mean AVF rates of included facilities increased from 63.7% in PY 2014 to 67.2% in PY 2016 ( p 0.05), and declined significantly in PY 2018–2020 to 64.1% in PY 2020, near AVF rates at the inception of program. Long-term TDC rates decreased from 10.4% in PY 2014 to 9.88% in PY 2015 ( p 0.05). AVF rates correlated positively and long-term TDC rates correlated negatively with star rating of facilities ( p Conclusion: As one of the first financial QIPs in healthcare, the ESRD QIP has not achieved the stated goals of the CMS to increase AVF access rates above 68% and reduce long-term TDC clinical rates below 10%. Systemic disparities in race, geographic region, economic status, healthcare access, and education of providers and patients prevent successful attainment of goal metrics.

Background The arteriovenous fistula (AVF) is the preferred hemodialysis access for end-stage renal disease (ESRD) patients. Yet, establishment of a functional AVF presents a challenge, even for the most experienced surgeons, since postoperative stenosis frequently occludes the AVF. Stenosis results from the loss of compliance in fibrotic areas of the fistula which turns intimal hyperplasia into an occlusive feature. Fibrotic remodeling depends on deposition and crosslinking of collagen by lysyl oxidase (LOX), an enzyme that catalyzes the deamination of lysine and hydroxylysine residues, facilitating intra/intermolecular covalent bonds. We postulate that pharmacological inhibition of lysyl oxidase (LOX) increases postoperative venous compliance and prevents stenosis in a rat AVF model. Methods LOX gene expression and vascular localization were assayed in rat AVFs and human pre-access veins, respectively. Collagen crosslinking was measured in humans AVFs that matured or failed, and in rat AVFs treated with β-aminopropionitrile (BAPN), an irreversible LOX inhibitor. BAPN was either injected systemically or delivered locally around rat AVFs using nanofiber scaffolds. The major endpoints were AVF blood flow, wall fibrosis, collagen crosslinking, and vascular distensibility. Results Non-maturation of human AVFs was associated with higher LOX deposition in pre-access veins (N=20, P=0.029), and increased trivalent crosslinks (N=18, P=0.027) in human AVF tissues. Systemic and local inhibition of LOX increased AVF distensibility, while reducing wall fibrosis and collagen crosslinking in rat fistulas. Conclusions Our results demonstrate that BAPN-mediated inhibition of LOX significantly improves vascular remodeling in experimental fistulas.

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of

Introduction Arteriovenous (AV) access thrombosis remains 1 of the most troubling AV access–related complications affecting hemodialysis patients. It necessitates an urgent and occasionally complicated thrombectomy procedure and increases the risk of AV access loss. AV access stenosis is found in the majority of thrombosed AV accesses. The routine use of AV access surveillance for the early detection and management of stenosis to reduce the thrombosis rate remains controversial. Methods We have conducted a multicenter, prospective, randomized clinical trial comparing the standard of care coupled with ultrasound dilution technique (UDT) flow measurement monthly surveillance with the standard of care alone. Results We prospectively randomized 436 patients with end-stage renal disease on hemodialysis with arteriovenous fistula (AVF) or arteriovenous graft (AVG) using cluster (shift) randomization to surveillance and control groups. There were no significant differences in the baseline demographic data between the 2 groups, except for ethnicity (P = 0.017). Patients were followed on average for 15.2 months. There were significantly less per-patient thrombotic events (Poisson rate) in the surveillance group (0.12/patient) compared with the control group (0.23/patient) (P = 0.012). There was no statistically significant difference in the total number of procedures between the 2 groups, irrespective of whether thrombectomy procedures were included or excluded, and no statistically significant differences in the rate of or time to the first thrombotic event or the number of catheters placed due to thrombosis. Conclusion The use of UDT flow measurement monthly AV access surveillance in this multicenter randomized controlled trial reduced the per-patient thrombotic events without significantly increasing the total number of angiographic procedures. Even though there is a trend, surveillance did not reduce the first thrombotic event rate., Graphical abstract

Background Intimal hyperplasia has been historically associated with improper venous remodeling and stenosis after creation of an arteriovenous fistula. Recently, however, we showed that intimal hyperplasia by itself does not explain the failure of maturation of 2-stage arteriovenous fistulas. We seek to evaluate whether intimal hyperplasia plays a role in the development of focal stenosis of an arteriovenous fistula. Methods This study compares intimal hyperplasia lesions in stenotic and nearby nonstenotic segments collected from the same arteriovenous fistula. Focal areas of stenosis were detected in the operating room in patients (n = 14) undergoing the second-stage vein transposition procedure. The entire vein was inspected, and areas of stenosis were visually located with the aid of manual palpation and hemodynamic changes in the vein peripheral and central to the narrowing. Stenotic and nonstenotic segments were documented by photography before tissue collection (14 tissue pairs). Intimal area and thickness, intima-media thickness, and intima to media area ratio were measured in hematoxylin and eosin stained cross-sections followed by pairwise statistical comparisons. Results The intimal area in stenotic and nonstenotic segments ranged from 1.25 to 11.61 mm2 and 1.29 to 5.81 mm2, respectively. There was no significant difference between these 2 groups (P = .26). Maximal intimal thickness (P = .22), maximal intima-media thickness (P = .13), and intima to media area ratio (P = .73) were also similar between both types of segments. Conclusion This preliminary study indicates that postoperative intimal hyperplasia by itself is not associated with the development of focal venous stenosis in 2-stage fistulas.

Defibrillation can be successfully provided by the subcutaneous implantable cardioverter defibrillator (ICD) without the leads. In contrast, traditional ICDs require leads that can cause central venous stenosis, lead-induced endocarditis, and carry the risk of tricuspid regurgitation by valve adhesion, perforation, coaptation interference, or entanglement. Central venous stenosis, infection, and tricuspid regurgitation are all critically important considerations in hemodialysis patients. Recent reports are supporting the use of subcutaneous ICDs in renal patients maintained on long-term hemodialysis. This article provides the risks associated with leads of traditional defibrillators and raises awareness of the subcutaneous ICD and their benefits for hemodialysis patients.

Amyloidoma is a highly unusual presentation of amyloidosis in tumoral or nodular form. Isolated soft tissue amyloidomas in individuals with end-stage renal disease on chronic hemodialysis is exceedingly rare, particularly in the era of advanced dialysis technologies. We report the case of a 55-year-old male with end-stage renal disease due to autosomal-dominant polycystic kidney disease, on HD for over 30 years, who was found to have soft-tissue, dialysis-related (β2 -microglobulin) amyloidomas (DRA). He presented with painful, palpable masses within the thoracic and abdominal walls. Serum β2 -microglobulin level was only mildly elevated at 24.9 mg/L. Biopsy confirmed amyloidosis with positivity for Congo Red staining and apple-green birefringence under polarized light. Amyloid subtyping with immunohistochemistry showed positive β2 -microglobulin staining within the deposits. Conservative therapy involving pain management and close monitoring resulted in eventual improvement in symptoms and thus proved to be a viable option for treatment.

Background The contribution of intimal hyperplasia (IH) to arteriovenous fistula (AVF) failure is uncertain. This observational study assessed the relationship between pre-existing, postoperative, and change in IH over time and AVF outcomes. Study Design Prospective cohort study with longitudinal assessment of IH at the time of AVF creation (pre-existing) and transposition (postoperative). Patients were followed up for up to 3.3 years. Setting & Participants 96 patients from a single center who underwent AVF surgery initially planned as a 2-stage procedure. Veins and AVF samples were collected from 66 and 86 patients, respectively. Matched-pair tissues were available from 56 of these patients. Predictors Pre-existing, postoperative, and change in IH over time. Outcomes Anatomic maturation failure was defined as an AVF that never reached a diameter > 6mm. Primary unassisted patency was defined as the time elapsed from the second-stage surgery to the first intervention. Measurements Maximal intimal thickness in veins and AVFs and change in intimal thickness over time. Results Pre-existing IH (>0.05mm) was present in 98% of patients. In this group, the median intimal thickness increased 4.40-fold (IQR, 2.17- to 4.94-fold) between AVF creation and transposition. However, this change was not associated with pre-existing thickness ( r 2 =0.002; P =0.7). Ten of 96 (10%) AVFs never achieved maturation, whereas 70% of vascular accesses remained patent at the end of the observational period. Postoperative IH was not associated with anatomic maturation failure using univariate logistic regression. Pre-existing, postoperative, and change in IH over time had no effects on primary unassisted patency. Limitations The small number of patients from whom longitudinal tissue samples were available and low incidence of anatomic maturation failure, which decreased the statistical power to find associations between end points and IH. Conclusions Pre-existing, postoperative, and change in IH over time were not associated with 2-stage AVF outcomes.

PURPOSE This study presents a method to quantify micro-stiffness variations in experimental arteriovenous fistulae (AVF). METHODS AVF created by anastomosing the superficial epigastric vein to the femoral artery in Sprague-Dawley rats were allowed to remodel for 21 days before being harvested and preserved in culture medium. A custom atomic force microscope was used to measure microvascular stiffness (Young's modulus) in three areas of the AVF: the inflow artery, the juxta-anastomotic area, and the outflow vein. Morphometric measurements and collagen and elastin contents were also determined. RESULTS Atomic force microscopy indentation revealed an increased stiffness in the juxta-anastomotic area of the AVF compared to the outflow vein and inflow artery. The juxta-anastomotic area was also significantly stiffer than the contralateral vein. The lack of elasticity (higher Young's modulus) of the juxta-anastomotic region was associated with a thicker vascular wall that was rich in collagen but poor in elastin. CONCLUSIONS This study demonstrates for the first time the feasibility of using atomic force microscopy to measure local stiffness variations in experimental AVF. This technique could be instrumental in advancing our understanding of how micro-spatial organization of the AVF wall determines the overall biomechanical performance of this type of vascular access.

Improving arteriovenous fistula (AVF) outcomes requires better understanding of the biology underlying maturation or failure. Our current knowledge of maturation relies on extrapolation from other vascular pathologies, which does not incorporate unique aspects of AVF remodeling. This study compares the RNA expression of pre-access (native) veins and AVFs with distinct maturation outcomes.Case-control study.64 patients undergoing 2-stage AVF surgeries at a single center. 19 native veins and 19 AVF samples were analyzed using RNA sequencing (RNA-seq). 58 native veins were studied using real-time polymerase chain reaction; 45, using immunohistochemistry; and 19, using Western blot analysis.RNA expression in native veins and AVFs.Anatomic nonmaturation, defined as an AVF that never achieved an internal diameter ≥ 6mm.Pre-access native veins and AVF samples were obtained from patients undergoing 2-stage AVF creation. Veins that subsequently matured or failed after access creation were analyzed using RNA-seq to search for genes associated with maturation failure. Genes associated with nonmaturation were confirmed using real-time polymerase chain reaction, immunohistochemistry, and Western blot analysis. In addition, the association between pre-access gene expression and postoperative morphology was evaluated. RNA-seq was also performed on AVFs to search for transcriptional differences between AVFs that matured and those that failed at the time of transposition.Pro-inflammatory genes (CSF3R, FPR1, S100A8, S100A9, and VNN2) were upregulated in pre-access veins that failed (false discovery rate 0.05), and their expression colocalized to smooth muscle cells. Expression of S100A8 and S100A9 correlated with postoperative intimal hyperplasia and the product of medial fibrosis and intimal hyperplasia (r=0.32-0.38; P0.05). AVFs that matured or failed were transcriptionally similar at the time of transposition.Small sample size, analysis of only upper-arm veins and transposed fistulas.Increased expression of proinflammatory genes in pre-access veins appears to be associated with greater risk for AVF nonmaturation.

Background: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality among patients with chronic kidney disease (CKD) with a glomerular filtration rate of < 60 mL/min/1.73 m2 body surface area. The availability of high-quality randomized controlled trial data to guide management for the population with CKD and ASCVD is limited. Understanding current practice patterns among providers caring for individuals with CKD and CVD is important in guiding future trial questions. Methods: A qualitative survey study was performed. An electronic survey regarding the diagnosis and management of CVD in patients with CKD was conducted using a convenience sample of 450 practicing nephrology and cardiology providers. The survey was administered using Qualtrics® (https://www.qualtrics.com). Results: There were a total of 113 responses, 81 of which were complete responses. More than 90% of the respondents acknowledged the importance of CVD as a cause of morbidity and mortality in patients with CKD. Outside the kidney transplant evaluation setting, 5% of the respondents would screen an asymptomatic patient with advanced CKD for ASCVD. Outside the kidney transplant evaluation scenario, the respondents did not opt for invasive management strategies in advanced CKD. Conclusions: The survey results reveal a lack of consensus among providers caring for patients with advanced CKD about the management of ASCVD in this setting. Future randomized controlled trials will be needed to better inform the clinical management of ASCVD in these patients. The limitations of the study include its small sample size and the relatively low response rate among the respondents.

Background: While transradial approach to conduct percutaneous coronary interventions offers multiple advantages, the procedure can cause radial artery damage and occlusion. Because radial artery is the preferred site for the creation of an arteriovenous fistula to provide dialysis, patients with chronic kidney disease are particularly dependent on radial artery for their long-term survival. Methods: In this retrospective study, we investigated the prevalence of chronic kidney disease in patients undergoing coronary interventions via radial artery. Stage of chronic kidney disease was based on estimated glomerular filtration rate and National Kidney Foundation - Kidney Disease Outcomes Quality Initiative guidelines. Results: A total of 497 patients undergoing transradial percutaneous coronary interventions were included. Over 70.4% (350/497) of the patients had chronic kidney disease. Stage II chronic kidney disease was observed in 243 (69%) patients (estimated glomerular filtration rate = 76.0 ± 8.4 mL/min). Stage III was observed in 93 (27%) patients (estimated glomerular filtration rate = 49 ± 7.5 mL/min). Stage IV chronic kidney disease was observed in 5 (1%) patients (estimated glomerular filtration rate = 25.6 ± 4.3 mL/min) and Stage V chronic kidney disease was observed in 9 (3%) patients (estimated glomerular filtration rate = 9.3 ± 3.5 mL/min). Overall, 107 of 350 patients (30%) had advanced chronic kidney disease, that is, stage III–V chronic kidney disease. Importantly, 14 of the 107 (13%) patients had either stage IV or V chronic kidney disease. Conclusion: This study finds that nearly one-third of the patients undergoing transradial percutaneous coronary interventions have advanced chronic kidney disease. Because many of these patients may require dialysis, the use of radial artery to conduct percutaneous coronary interventions must be carefully considered in chronic kidney disease population.

Defibrillation can be successfully provided by the subcutaneous implantable cardioverter defibrillator (ICD) without the leads. In contrast, traditional ICDs require leads that can cause central venous stenosis, lead-induced endocarditis, and carry the risk of tricuspid regurgitation by valve adhesion, perforation, coaptation interference, or entanglement. Central venous stenosis, infection, and tricuspid regurgitation are all critically important considerations in hemodialysis patients. Recent reports are supporting the use of subcutaneous ICDs in renal patients maintained on long-term hemodialysis. This article provides the risks associated with leads of traditional defibrillators and raises awareness of the subcutaneous ICD and their benefits for hemodialysis patients.

Not infrequently, interventionalists are faced with a patient with increased blood pressure who is about to undergo a dialysis access intervention such as tunneled hemodialysis catheter, percutaneous balloon angioplasty, or declotting procedure for a clotted arteriovenous access. This can frequently create a dilemma as functional dialysis access is needed to provide dialysis therapy and delaying treatment could result in a life-threatening situation, particularly in the presence of hyperkalemia. This article investigates hypertension in patients undergoing percutaneous dialysis access interventions and provides guidance to their management.

The frequency of primary failure in arteriovenous fistulas (AVFs) remains unacceptably high. This lack of improvement is due in part to a poor understanding of the pathobiology underlying AVF nonmaturation. This observational study quantified the progression of three vascular features, medial fibrosis, intimal hyperplasia (IH), and collagen fiber organization, during early AVF remodeling and evaluated the associations thereof with AVF nonmaturation. We obtained venous samples from patients undergoing two-stage upper-arm AVF surgeries at a single center, including intraoperative veins at the first-stage access creation surgery and AVFs at the second-stage transposition procedure. Paired venous samples from both stages were used to evaluate change in these vascular features after anastomosis. Anatomic nonmaturation (AVF diameter never ≥6 mm) occurred in 39 of 161 (24%) patients. Neither preexisting fibrosis nor IH predicted AVF outcomes. Postoperative medial fibrosis associated with nonmaturation (odds ratio [OR], 1.55; 95% confidence interval [95% CI], 1.05 to 2.30; P=0.03, per 10% absolute increase in fibrosis), whereas postoperative IH only associated with failure in those individuals with medial fibrosis over the population's median value (OR, 2.63; 95% CI, 1.07 to 6.46; P=0.04, per increase of 1 in the intima/media ratio). Analysis of postoperative medial collagen organization revealed that circumferential alignment of fibers around the lumen associated with AVF nonmaturation (OR, 1.38; 95% CI, 1.03 to 1.84; P=0.03, per 10° increase in angle). This study demonstrates that excessive fibrotic remodeling of the vein after AVF creation is an important risk factor for nonmaturation and that high medial fibrosis determines the stenotic potential of IH.

Introduction Ischemic monomelic neuropathy (IMN) is the most dreaded complication of an arteriovenous access creation. While uncommon, it can lead to pain, paresthesia or/and hand weakness. Creation of an arteriovenous connection causing a sudden diversion of blood away from the nerves can lead to ischemic injury to the neural tissue and cause IMN. Immediate surgical ligation has been traditionally recommended to limit ongoing neural tissue injury. Case description We present two diabetic patients who developed IMN after the creation of a left upper extremity brachial-cephalic fistula and refused to undergo surgical ligation. The clinical examination revealed paresthesia localized to the volar aspect of the left forearm with mild weakness of the thumb, index and middle finger. Rehabilitation therapy was initiated in both and revealed a significant improvement in weakness but paresthesia persisted. Fistula maturation was achieved in both patients with an access flow of 1100-1200 cc/min. At 4 months, fistula was used successfully for dialysis in both patients. At a follow-up of 11 months, hand weakness did not progress and paresthesia disappeared. Conclusions These cases demonstrate sensory-motor improvement with time and rehabilitation therapy and challenge the traditional approach of fistula ligation. The approach presented in this paper also results in the preservation of the lifeline of a patient. Future investigations should focus on identifying candidates who could benefit from physical therapy and rehabilitation.

Hyponatremia is associated with increased morbidity and mortality. Water restriction is usually the prescribed treatment for most forms of asymptomatic hyponatremia. An oral vasopressin V2-receptor antagonist, tolvaptan has been successfully used in the treatment of asymptomatic hyponatremia. In this retrospective study, tolvaptan (n=40) and a control group (n=40) were compared for asymptomatic hyponatremia etiology and response to treatment. The syndrome of inappropriate anti-diuretic hormone (SIADH) and congestive heart failure (CHF) were the most common causes of asymptomatic hyponatremia that were treated with tolvaptan. Of note, the cause of hyponatremia was not clarified in 50% of the control and 10% of the tolvaptan group. In the tolvaptan group, serum sodium concentration increased from 125±4.2 to 136±2.1 mEq/L (mean±SD, P

Renal artery stenosis (RAS) due to atherosclerosis continues to be a major cause of secondary hypertension. It can also lead to renal dysfunction due to ischemic nephropathy. While major clinical trials have emphasized that medical management should be preferred over angioplasty and stenting for the treatment of renal artery stenosis, clinical scenarios continue to raise doubts about the optimal management strategy. Herein, we present two cases that were admitted with hypertensive emergency and renal function deterioration. Medical therapy failed to control the blood pressure and in one patient, renal failure progressed to a point where renal replacement therapy was required. Both patients underwent angioplasty (for >90% stenosis) and stent insertion with successful resolution of stenosis by interventional radiology. Postoperatively, blood pressure gradually decreased with improvement in serum creatinine. Dialysis therapy was discontinued. At 4- and 8-month follow-up, both patients continue to do well with blood pressure readings in the 132-145/70-90 mmHg range. This article highlights the importance of percutaneous interventions in the management of atherosclerotic RAS and calls for heightened awareness and careful identification of candidates who would benefit from angioplasty and stent insertion.

Takayasu’s arteritis is a rare disorder characterized by granulomatous and necro-inflammatory disease of the aorta and its major branches. Its etiology remains unknown. We report a young woman with Takayasu’s arteritis affecting the aortic arch, carotid, mesenteric, celiac and bilateral renal arteries resulting in severe hypertension, unilateral renal atrophy and renal insufficiency. The immunosuppressive therapy did not halt the progression of her vascular disease, which required revascularization procedures on numerous occasions. Here, the clinical manifestations and histopathological features of Takayasu’s arteritis are reviewed. In addition, the available medical treatment options including glucocorticoids, cytotoxic agents and TNF-alpha inhibitors are discussed. Furthermore, current revascularization procedures such as percutaneous transluminal angioplasty and reconstructive vascular surgery in the treatment of occlusive vasculopathy due to Takayasu’s arteritis are discussed. Although the prognosis of this debilitating disease has improved over the past two decades, a better understanding of its etiology and pathogenesis will facilitate the discovery of effective target-specific treatment strategies with a narrow adverse effects profile.

The arteriovenous fistula (AVF) is the preferred hemodialysis access type because it has better patency rates and fewer complications than other access types. However, primary failure remains a common problem impeding AVF maturation and adding to patients' morbidity and mortality. Juxta-anastomotic (or inflow) stenosis is the most common reason leading to primary failure, and percutaneous transluminal angioplasty continues to be the gold-standard treatment with excellent success rates. Intimal hyperplasia (IH) has been traditionally blamed as the main pathophysiologic culprit, but new evidence raises doubts regarding the contribution of IH alone to primary failure. We report a 64-year-old man with a 2-stage brachiobasilic AVF that was complicated by failure 4 months after creation. An angiogram showed multiple juxta-anastomotic and midfistula stenotic lesions. Percutaneous transluminal angioplasty was successful in assisting maturation and subsequently cannulating the AVF for hemodialysis treatment. We failed to identify the underlying cause of stenosis because biopsy specimens from fistula tissue obtained at the time of transposition revealed no occlusive IH. This case emphasizes the need for additional research on factors contributing to AVF failure besides IH and highlights the need for more therapeutic options to reduce AVF failure rate.

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.

Abnormal renal function is an independent risk factor for cardiac implantable electronic device (CIED) infection. The risk of CIED infection increases as the degree of renal dysfunction worsens with the highest risk observed in patients with stage V chronic kidney disease. A significant portion of these patients use a tunneled hemodialysis catheter (TDC) for dialysis therapy. These devices are associated with very high rates of catheter-related bacteremia (1.6–5.5 episodes of bacteremia per 1000 catheter days), and have been known to cause infection of CIED indwelling in the bloodstream. In this context, the cardiac device is exposed to the risk of infection due to the presence of renal failure and episodes of bacteremia related to TDCs. Both increase the risk of CIED infection. Once infected, a cardiac rhythm device carries a marked increase in morbidity and mortality. In this context, the combination of a TDC and a CIED indwelling in the bloodstream becomes a potentially deadly combination. Recent data have emphasized that epicardial CIED implantation reduces cardiac device infection in TDC patients. This report highlights the risk of CIED infection in renal patients, presents TDC’s contribution to the cardiac device infection, and suggests recommendations to minimize the risk of CIED infection in chronic hemodialysis patients dialyzing with a TDC.

High brachial artery bifurcation (HiBAB) is not a rare occurrence. Recent data have emphasized that HiBAB can have major clinical implications including high failure rate and decreased functional patency of an arteriovenous (AV) fistula. In this retrospective study, we investigated the incidence of HiBAB. Patients with advanced chronic kidney disease and end-stage renal disease on chronic hemodialysis undergoing preoperative vascular mapping for the creation of an AV access were included in this analysis. Ultrasound examination was used to map the arteries of the upper extremities. Four hundred and eighty-one arms in 340 patients were examined (right arm = 181, left arm = 300). Sixty-nine of the 481 (12.3%) demonstrated HiBAB. The internal diameter of the radial and ulnar arteries measured at the elbow region was found to be 2.9 ± 0.8 and 3.6 ± 1.0 mm, respectively (p = 0.0001). There were no statistically significant differences in terms of race, gender, and right versus left arms regarding the incidence of HiBAB. As HiBAB can be present in a significant number of patients and have an impact on the AV access, its presence should be evaluated during vascular mapping prior to an AV access creation.

The development of interventional nephrology has undoubtedly led to an improvement in patient care at many facilities across the United States. However, these services have traditionally been offered by interventional nephrologists in the private practice arena. While interventional nephrology was born in the private practice setting, several academic medical centers across the United States have now developed interventional nephrology programs. University Medical Centers (UMCs) that offer interventional nephrology face challenges, such as smaller dialysis populations, limited financial resources, and real or perceived political "turf" issues." Despite these hurdles, several UMCs have successfully established interventional nephrology as an intricate part of a larger nephrology program. This has largely been accomplished by consolidating available resources and collaborating with other specialties irrespective of the size of the dialysis population. The collaboration with other specialties also offers an opportunity to perform advanced procedures, such as application of excimer laser and endovascular ultrasound. As more UMCs establish interventional nephrology programs, opportunities for developing standardized training centers will improve, resulting in better quality and availability of nephrology-related procedures, and providing an impetus for research activities.

Even though many positive changes were ushered in by the KDOQI guidelines and the Fistula First Breakthrough Initiative, tunneled hemodialysis catheters remain an essential piece of the dialysis access puzzle. Their use is, however, attended by a multitude of complications and morbidity of which the general nephrologist must be aware. The purpose of this article is to review for the general nephrologist the infectious and non-infectious problems that often complicate the use of hemodialysis catheters.

To elucidate the source of neointimal cells, experimental fistulas were created in Lewis wild-type (WT) and transgenic rats that constitutively expressed the green fluorescent protein (GFP) in all tissues. Arteriovenous fistula (AVFs) were created by anastomosing the left renal vein to the abdominal aorta. The contribution of bone marrow (BM)-derived cells to the AVF neointima was examined in lethally irradiated WT rats that had been rescued with GFP BM cells. Neointimal cells in these chimeric rats were mostly GFP negative indicating the non-BM origin of those cells. Then, the contribution of arterial cells to the AVF neointima was assessed in a fistula made with a GFP aorta that had been implanted orthotopically into a WT rat. Most of the neointimal cells were also GFP negative demonstrating that AVF neointimal cells are not derived from the feeding artery. Finally to study local resident cells contribution to the formation of neointimal lesions, a composite fistula was created by interposing a GFP vein between the renal vein and the aorta in a WT recipient rat. GFP neointimal cells were only found in the transplanted vein. This study suggests that neointimal cells originate from the local resident cells in the venous limb of the fistula.

The foundation of endovascular procedures by nephrologists was laid in the private practice arena. Because of political issues such as training, credentialing, space and equipment expenses, and co-management concerns surrounding the performance of dialysis-access procedures, the majority of these programs provided care in an outpatient vascular access center. On the basis of the improvement of patient care demonstrated by these centers, several nephrology programs at academic medical centers have also embraced this approach. In addition to providing interventional care on an outpatient basis, academic medical centers have taken a step further to expand collaboration with other specialties with similar expertise (such as with interventional radiologists and cardiologists) to enhance patient care and research. The enthusiastic initiative, cooperative, and mutually collaborative efforts used by academic medical centers have resulted in the successful establishment of interventional nephrology programs. This article describes various models of interventional nephrology programs at academic medical centers across the United States.

Transvenous leads of cardiac rhythm devices (CRDs) are known to cause central stenosis and are vulnerable to contamination during hemodialysis access-related bacteremia. In this retrospective study, nine consecutive chronic hemodialysis patients with transvenous CRD infection due to dialysis access-related bacteremia and recurrent central stenosis are presented. Four patients with tunneled hemodialysis catheters (TDCs) and three with arteriovenous grafts experienced access-related bacteremia that spread to the transvenous CRD. Two patients required repeated angioplasty procedures (less than 3 months apart) for central venous stenosis. Transvenous CRD was removed and replaced with an epicardial system in all. One patient with TDC switched to peritoneal dialysis and did not experience infection of the epicardial system despite two episodes of peritonitis. The remaining TDC (n =3 ) and graft patients (n = 3) received a new TDC after the resolution of bacteremia. While all six experienced on average 1.5 episodes of catheter-related bacteremia (average follow-up = 14.5 months), none developed infection of the epicardial system. The patients with central stenosis have required only one angioplasty each for the past 8 and 6 months. To the best of our knowledge this is the first study to suggest that an epicardial approach might be a preferred method over transvenous leads for chronic hemodialysis patients.

Traction and cutdown techniques can successfully remove a tunneled dialysis catheter (TDC) in a great majority of patients. However, these methods may not be successful in patients with catheters that are tethered or attached to the central veins or the atrium. A forceful application of traction can lead to catheter breakage with subsequent retention of the broken piece and carries a potential risk of vascular and atrial wall avulsion. Open thoracotomy has been employed to remove an attached TDC. However, this procedure is invasive and bears a significant morbidity. This report presents three cases of tethered TDCs that underwent laser sheath extraction. The TDCs had been in place for an average of 26 months. The patients underwent initial unsuccessful removal attempt using the traction method with surgical exploration all the way to the venotomy site. The laser technique that is used to remove pacemaker/implantable cardioverter defibrillator leads was then applied to these stuck catheters. All three catheters were successfully removed without any damage to the catheter, central veins, or the right atrium. There were no retained catheter fragments left in the central veins or the atrium. One patient demonstrated a significant thrombus that extended from the tip of the catheter all the way to the right ventricle. The external sheath of the laser device successfully aspirated the thrombus. There were no procedure-related complications. In this small series, a laser sheath successfully extracted tethered dialysis catheters. The study found the procedure to be effective, easy to perform, and minimally invasive. We suggest that this approach be considered for the removal of tethered catheters that cannot be removed using traditional approaches.