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Background Performing catheter-care observations in outpatient hemodialysis facilities are one of the CDC9s core interventions, which have been proven to reduce bloodstream infections. However, staff have many competing responsibilities. Efforts to increase and streamline the process of performing observations are needed. We developed an electronic catheter checklist, formatted for easy access with a mobile device, and conducted a pilot project to determine the feasibility of implementing it in outpatient dialysis facilities. Methods The tool contained the following content: (1) patient education videos; (2) catheter-care checklists (connection, disconnection, and exit-site care); (3) prepilot and postpilot surveys; and (4) a pilot implementation guide. Participating hemodialysis facilities performed catheter-care observations on either a weekly or monthly schedule and provided feedback on implementation of the tool. Results The pilot data were collected from January 6 through March 12, 2020, at seven participating facilities. A total of 954 individual observations were performed. The catheter-connection, disconnection, and exit-site steps were performed correctly for most individual steps; however, areas for improvement were (1) allowing for appropriate antiseptic dry time, (2) avoiding contact after antisepsis, and (3) applying antibiotic ointment to the exit site. Postpilot feedback from staff was mostly favorable. Use of the electronic checklists facilitated patient engagement with staff and was preferred over paper checklists, because data are easily downloaded and available for use in facility Quality Assurance and Performance Improvement (QAPI) meetings. The educational video content was a unique learning opportunity for both patients and staff. Conclusions Converting the CDC9s existing catheter checklists to electronic forms reduced paperwork and improved the ease of collating data for use during QAPI meetings. An additional benefit was the educational content provided on the tablet, which was readily available for viewing by patients and staff while in the hemodialysis facility.

The coronavirus disease 2019 (COVID-19) pandemic is unprecedented and information about the severe acute respiratory syndrome coronavirus 2 is evolving rapidly. New York is one of the epicenters of the COVID-19 outbreak in the United States, reporting >1000 confirmed cases as of March 17, 2020, and cases are escalating exponentially. The majority of cases are in Westchester County ( n =220) and New York City (NYC; n =463), which includes Bronx (1). The local index patient case was a Westchester man who became ill on February 22, was not associated with a recent travel exposure to a country on the watch list (China, Iran, South Korea, and Italy), or known to have had direct contact with a COVID-19–confirmed patient. At the present time it is estimated that community-wide transmission accounts for 87% of confirmed cases. Nephrologists in the Bronx have been handicapped in managing patients with ESKD during the early weeks of the COVID-19 pandemic due to the limitations of available rapid testing for severe acute respiratory syndrome coronavirus 2. Montefiore Medical Center, located in the north Bronx in close proximity to Westchester, has been one of the main tertiary care hospitals in NYC caring for persons under investigation (PUIs) and for COVID-19–confirmed patients. Our nephrology division’s clinical faculty care for approximately 850 patients with ESKD (approximately 800 on hemodialysis and approximately 50 on peritoneal dialysis) in 12 outpatient hemodialysis facilities (two Fresenius and 10 DaVita facilities) in the Bronx. We report our experience with caring for the ESKD population and patients who are hospitalized with AKI in the Bronx during the first 3 weeks of the local NYC COVID-19 pandemic. Strategies proposed for the prevention and management of COVID-19 transmission for patients with ESKD in the outpatient dialysis facilities have been dynamic. The American Society of Nephrology’s (ASN’s) Nephrologists Transforming …

Background Patients with ESKD who are on chronic hemodialysis have a high burden of comorbidities that may place them at increased risk for adverse outcomes when hospitalized with COVID-19. However, data in this unique patient population are limited. The aim of our study is to describe the clinical characteristics and short-term outcomes in patients on chronic hemodialysis who require hospitalization for COVID-19. Methods We performed a retrospective study of 114 patients on chronic hemodialysis who were hospitalized with COVID-19 at two major hospitals in the Bronx from March 9 to April 8, 2020 during the surge of SARS-CoV-2 infections in New York City. Patients were followed during their hospitalization through April 22, 2020. Comparisons in clinical characteristics and laboratory data were made between those who survived and those who experienced in-hospital death; short-term outcomes were reported. Results Median age was 64.5 years, 61% were men, and 89% were black or Hispanic. A total of 102 (90%) patients had hypertension, 76 (67%) had diabetes mellitus, 63 (55%) had cardiovascular disease, and 30% were nursing-home residents. Intensive care unit (ICU) admission was required in 13% of patients, and 17% required mechanical ventilation. In-hospital death occurred in 28% of the cohort, 87% of those requiring ICU, and nearly 100% of those requiring mechanical ventilation. A large number of in-hospital cardiac arrests were observed. Initial procalcitonin, ferritin, lactate dehydrogenase, C-reactive protein, and lymphocyte percentage were associated with in-hospital death. Conclusions Short-term mortality in patients on chronic hemodialysis who were hospitalized with COVID-19 was high. Outcomes in those requiring ICU and mechanical ventilation were poor, underscoring the importance of end-of-life discussions in patients with ESKD who are hospitalized with severe COVID-19 and the need for heightened awareness of acute cardiac events in the setting of COVID-19. Elevated inflammatory markers were associated with in-hospital death in patients with ESKD who were hospitalized with COVID-19.

Bloodstream infections are an important cause of hospitalizations, morbidity, and mortality in patients receiving hemodialysis. Eliminating bloodstream infections in the hemodialysis setting has been the focus of the Centers for Disease Control and Prevention (CDC) Making Dialysis Safer for Patients Coalition and, more recently, the CDC's partnership with the American Society of Nephrology's Nephrologists Transforming Dialysis Safety Initiative. The majority of vascular access-associated bloodstream infections occur in patients dialyzing with central vein catheters. The CDC's core interventions for bloodstream infection prevention are the gold standard for catheter care in the hemodialysis setting and have been proven to be effective in reducing catheter-associated bloodstream infection. However, in the United States hemodialysis catheter-associated bloodstream infections continue to occur at unacceptable rates, possibly because of lapses in adherence to strict aseptic technique, or additional factors not addressed by the CDC's core interventions. There is a clear need for novel prophylactic therapies. This review highlights the recent advances and includes a discussion about the potential limitations and adverse effects associated with each option.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Background COVID-19 mortality disproportionately affects the Black population in the United States (US). To explore this association a cohort study was undertaken. Methods We assembled a cohort of 505,992 patients receiving ambulatory care at Bronx Montefiore Health System (BMHS) between 1/1/18 and 1/1/20 to evaluate the relative risk of hospitalization and death in two time-periods, the pre-COVID time-period (1/1/20–2/15/20) and COVID time-period (3/1/20–4/15/20). COVID testing, hospitalization and mortality were determined with the Black and Hispanic patient population compared separately to the White population using logistic modeling. Evaluation of the interaction of pre-COVID and COVID time periods and race, with respect to mortality was completed. Findings A total of 9,286/505,992 (1.8%) patients were hospitalized during either or both pre-COVID or COVID periods. Compared to Whites the relative risk of hospitalization of Black patients did not increase in the COVID period (p for interaction=0.12). In the pre- COVID period, compared to Whites, the odds of death for Blacks and Hispanics adjusted for comorbidity was statistically equivalent. In the COVID period compared to Whites the adjusted odds of death for Blacks was 1.6 (95% CI 1.2–2.0, p = 0.001). There was a significant increase in Black mortality risk from pre-COVID to COVID periods (p for interaction=0.02). Adjustment for relevant clinical and social indices attenuated but did not fully explain the observed difference in Black mortality. Interpretation The BMHS COVID experience demonstrates that Blacks do have a higher mortality with COVID incompletely explained by age, multiple reported comorbidities and available metrics of sociodemographic disparity. Funding N/A

Background Reports from centers treating patients with coronavirus disease 2019 (COVID-19) have noted that such patients frequently develop AKI. However, there have been no direct comparisons of AKI in hospitalized patients with and without COVID-19 that would reveal whether there are aspects of AKI risk, course, and outcomes unique to this infection. Methods In a retrospective observational study, we evaluated AKI incidence, risk factors, and outcomes for 3345 adults with COVID-19 and 1265 without COVID-19 who were hospitalized in a large New York City health system and compared them with a historical cohort of 9859 individuals hospitalized a year earlier in the same health system. We also developed a model to identify predictors of stage 2 or 3 AKI in our COVID-19. Results We found higher AKI incidence among patients with COVID-19 compared with the historical cohort (56.9% versus 25.1%, respectively). Patients with AKI and COVID-19 were more likely than those without COVID-19 to require RRT and were less likely to recover kidney function. Development of AKI was significantly associated with male sex, Black race, and older age (>50 years). Male sex and age >50 years associated with the composite outcome of RRT or mortality, regardless of COVID-19 status. Factors that were predictive of stage 2 or 3 AKI included initial respiratory rate, white blood cell count, neutrophil/lymphocyte ratio, and lactate dehydrogenase level. Conclusions Patients hospitalized with COVID-19 had a higher incidence of severe AKI compared with controls. Vital signs at admission and laboratory data may be useful for risk stratification to predict severe AKI. Although male sex, Black race, and older age associated with development of AKI, these associations were not unique to COVID-19.

The cannulation technique of a hemodialysis vascular access has remained controversial with differing viewpoints. The quality of dialysis, overall patient safety, and individual dialysis experience often dictate the type of cannulation technique used in clinical practice. The three commonly used techniques to access a hemodialysis vascular access are the rope ladder, area, and buttonhole. Although the buttonhole technique has been around since the mid-1970s, the dialysis community remains divided on its suitability for routine use to provide maintenance hemodialysis therapy. The proponents of this technique value the ease of cannulation with less pain and discomfort whereas the opponents highlight the increased risk of infection. The actual clinical evidence from the United States is limited and remains inconclusive. The current review provides an overview of the available experience from the United States, highlighting the correct technique of creating a buttonhole, summarizing the current evidence, and recommending a need for larger randomized controlled studies in both in-center and home hemodialysis populations.

Tunneled central venous catheters used for the provision of hemodialysis are associated with excess morbidity and mortality. Catheter related exit site and blood stream infections are major risks of their use. Although catheter-avoidance is the best strategy to reduce infections and mortality in the hemodialysis population, the use of catheters remains unacceptably high. In this review, the existing clinical practice guidelines for the prevention of hemodialysis catheter associated infections are outlined, and a comprehensive evidenced-based summary of interventions is provided. This includes details about the use of topical antimicrobial ointments and dressings, intranasal ointment application, prophylactic use of antibiotic and non-antibiotic catheter lock solutions, and catheter hub devices for the prevention of catheter blood stream infections.

Central venous catheters are used frequently in patients on hemodialysis as a bridge to a permanent vascular access. They are prone to frequent complications, including catheter-related bloodstream infection, catheter dysfunction, and central vein obstruction. There is a compelling need to develop new drugs or devices to prevent central venous catheter complications. We convened a multidisciplinary panel of experts to propose standardized definitions of catheter end points to guide the design of future clinical trials seeking approval from the Food and Drug Administration. Our workgroup suggests diagnosing catheter-related bloodstream infection in catheter-dependent patients on hemodialysis with a clinical suspicion of infection (fever, rigors, altered mental status, or unexplained hypotension), blood cultures growing the same organism from the catheter hub and a peripheral vein (or the dialysis bloodline), and absence of evidence for an alternative source of infection. Catheter dysfunction is defined as the inability of a central venous catheter to (1) complete a single dialysis session without triggering recurrent pressure alarms or (2) reproducibly deliver a mean dialysis blood flow of >300 ml/min (with arterial and venous pressures being within the hemodialysis unit parameters) on two consecutive dialysis sessions or provide a Kt/V≥1.2 in 4 hours or less. Catheter dysfunction is defined only if it persists, despite attempts to reposition the patient, reverse the arterial and venous lines, or forcefully flush the catheter. Central vein obstruction is suspected in patients with >70% stenosis of a central vein by contrast venography or the equivalent, ipsilateral upper extremity edema, and an existing or prior history of a central venous catheter. There is some uncertainty about the specific criteria for these diagnoses, and the workgroup has also proposed future high-priority studies to resolve these questions.

Background Classification and treatment decisions in lupus nephritis (LN) are largely based on renal histology. Single-cell RNA sequencing (scRNAseq) analysis may accurately differentiate types of renal involvement at the transcriptomic level, and better inform treatment decisions and prognosis. Methods scRNAseq was performed on kidney and non-lesional skin tissue collected from 20 SLE patients undergoing a clinically indicated renal biopsy. Cell types were determined using principal component analysis and t-distributed stochastic neighbor embedding (tSNE) plotting, resulting in the definitive identification of keratinocytes, tubular cells, mesangial cells, fibroblasts, endothelial cells, and leukocytes. Results LN patients expressed upregulated IFN response genes in both their tubular cells and keratinocytes. This IFN response signature in tubular cells predicted poor response to therapy 6 months post-biopsy. Tubular cells of non-responder patients also expressed upregulated extracellular matrix proteins and fibrotic markers (figure 1A and 1B). Using logistic regression analysis, a 4-gene tubular fibrosis score was created and able to predict response to treatment with an area under curve of 0.9 (figure 1C). Keratinocytes of non-responders also upregulated certain extracellular matrix genes and this response was not observed in peripheral blood mononuclear cells. Differential expression analysis between histology classes indicated an upregulation of IFN and TNF signaling in the tubular cells of patients with proliferative LN compared with membranous. Conclusions scRNAseq from 2–10 mm of renal biopsy tissue in SLE can differentiate between the different classes of LN, and provide important insights into potential pathogenic mechanisms. Further, changes in the skin of LN patients can provide a useful source of biomarkers and may reflect important information concerning concurrent kidney pathological events. Funding Source(s): This work was supported by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network. AMP is a public-private partnership (AbbVie, Arthritis Foundation, Bristol-Myers Squibb, Foundation for the National Institutes of Health, Lupus Foundation of America, Lupus Research Alliance, Merck Sharp and Dohme, National Institute of Allergy and Infectious Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Pfizer, Rheumatology Research Foundation, Sanofi, and Takeda Pharmaceuticals) created to develop new ways of identifying and validating promising biological targets for diagnostics and drug development. Funding was provided through grants from the National Institutes of Health (UH2-AR067676, UH2-AR067677, UH2-AR067679, UH2-AR067681, UH2-AR067685, UH2-AR067688, UH2-AR067689, UH2-AR067690, UH2-AR067691, UH2-AR067694, and UM2-AR067678).

Background and objectives This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever). Design, setting, participants, & measurements We enrolled adults and children with proteinuria ≥0.5 g/d at the time of first clinically indicated renal biopsy at 21 sites in North America from April 2010 to June 2014 into a prospective cohort study. NEPTUNE central pathologists assigned participants to minimal-change disease (MCD), FSGS, membranous nephropathy, or other glomerulopathy cohorts. Outcome measures for this analysis were (1) CRever with urine protein-to-creatinine ratio (UPC)

Tunneled central venous catheters used for the provision of hemodialysis are associated with excess morbidity and mortality. Catheter related exit site and blood stream infections are major risks of their use. Although catheter-avoidance is the best strategy to reduce infections and mortality in the hemodialysis population, the use of catheters remains unacceptably high. In this review, the existing clinical practice guidelines for the prevention of hemodialysis catheter associated infections are outlined, and a comprehensive evidenced-based summary of interventions is provided. This includes details about the use of topical antimicrobial ointments and dressings, intranasal ointment application, prophylactic use of antibiotic and non-antibiotic catheter lock solutions, and catheter hub devices for the prevention of catheter blood stream infections.

Lupus nephritis (LN) occurs in up to 50% of patients with systemic lupus erythematosus (SLE), and is a major contributor to mortality and morbidity. LN presents as a highly heterogeneous disease both in histopathology and response to therapy. The molecular and cellular processes leading to renal damage and to the heterogeneity of the disease are not well understood. To elucidate the processes underpinning the heterogeneity of LN, we applied singlecell RNA-sequencing (scRNA-seq) to renal biopsies from LN patients. Skin biopsies were evaluated as a source of biomarkers for monitoring kidney disease. Type-I interferon (IFN) response signatures were identified in tubular cells and keratinocytes, differentiating LN patients from healthy controls. Non-responders associated with higher IFN signatures in both tissue compartments. Moreover, non-response was also associated with a fibrotic signature in the tubular cells. Receptor-ligand interaction analysis indicated that the fibrotic process is likely mediated by FGF receptors with the initiating signal originating from infiltrating leukocytes. Differential expression analysis of tubular cells between proliferative and membranous LN pointed to several fibrosis-relevant pathways, which may offer insight into their histological differences. In summary, scRNA-seq was applied to LN to deconstruct its heterogeneity and provide novel targets for personalized approaches to therapy.

The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.

Understanding healthcare providers' preferences, values, and beliefs around AVF eligibility is important to explain variability in practice. We conducted a survey of international surgeons, using hypothetical patient scenarios, to assess resources used, variables, perceived barriers, and absolute contraindications to access creation. A total of 134 surgeons completed the survey. Venous duplex ultrasound mapping (VDUM) was offered to all patients by 90% of US, 68% Canadian, and 63% European respondents. VDUM altered clinical decision less than 25% of the time for 33% American, 48% Canadian, and 85% European surgeons. Increased comorbidities and previous failed access were deterrents to AVF creation as was vessel size. Second choice access was the AV graft in the US and Europe and the catheter in Canada. Absolute contraindications to AVF creation included patient life expectancy

This review addresses the types of vascular access available for patients who need therapeutic apheresis (TA). As in hemodialysis, vascular access for TA is chosen based on type of procedure prescribed, the patient's vascular anatomy, the acuity, frequency and duration of treatment, and the underlying disease state. The types of access available include peripheral vein cannulation, central venous catheters: including nontunneled and tunneled catheters, arterio-venous grafts and arterio-venous fistulas. Peripheral veins and central venous catheters are most frequently utilized for the acute administration of TA, and may be used over a period of weeks to months. Arterio-venous grafts and fistulas are not commonly used in TA procedures, but are an option in patients with an anticipated long course of TA, usually for a period of several months or years. The types and frequency of complications associated with various types of vascular access, including: access dysfunction and infections are reviewed, and strategies for their prevention and management are offered.

Vascular access dysfunction is one of the leading causes of morbidity and mortality among end-stage renal disease patients. Vascular access dysfunction exists in all three types of available accesses: arteriovenous fistulas, arteriovenous grafts, and tunneled catheters. To improve clinical research and outcomes in hemodialysis (HD) access dysfunction, the development of a multidisciplinary network of collaborative investigators with various areas of expertise, and common standards for terminology and classification in all vascular access types, is required. The North American Vascular Access Consortium (NAVAC) is a newly formed multidisciplinary and multicenter network of experts in the area of HD vascular access, who include nephrologists and interventional nephrologists from the United States and Canada with: (1) a primary clinical and research focus in HD vascular access dysfunction, (2) national and internationally recognized experts in vascular access, and (3) a history of productivity measured by peer-reviewed publications and funding among members of this consortium. The consortium's mission is to improve the quality and efficiency in vascular access research, and impact the research in the area of HD vascular access by conducting observational studies and randomized controlled trials. The purpose of the consortium's initial manuscript is to provide working and standard vascular access definitions relating to (1) epidemiology, (2) vascular access function, (3) vascular access patency, and (4) complications in vascular accesses relating to each of the vascular access types.

Central venous catheter-related infections have been associated with high morbidity, mortality, and costs. Catheter use in chronic hemodialysis patients has been recognized as distinct from other patient populations who require central venous access, leading to recent adaptations in guidelines-recommended diagnosis for catheter-related bacteremia (CRB). This review will discuss the epidemiology and pathogenesis of hemodialysis CRB, in addition to a focus on interventions that have favorably affected CRB outcomes. These include: (1) the use of prophylactic topical antimicrobial ointments at the catheter exit site, (2) the use of prophylactic catheter locking solutions for the prevention of CRB, (3) strategies for management of the catheter in CRB, and (4) the use of vascular access managers and quality initiative programs.

In the United States, over 340,000 patients have end-stage renal disease treated by hemodialysis (HD) and are dependent on a reliable vascular access. In over 80% of patients initiating HD, this access is the central venous catheter (CVC). Although the CVC has many advantages that make it desirable for dialysis initiation—ease of insertion, unnecessary maturation time, and availability for immediate use—it is not without significant disadvantages. The substantial morbidity and mortality associated with CVC use has been well documented in the literature. 1 , 2 Initiating and maintaining HD patients using a CVC is suboptimal from the perspective of both patient care and associated long-term costs. Yet, in the United States, the most common HD access-related event is replacement of any vascular access type with a CVC. 3 Although in recent years greater effort has be made to reduce CVC use, some patients are unable to have a functioning arteriovenous fistula or graft created due to exhaustion of vessels from previous permanent accesses or limiting comorbidities. In patients dependent on long-term CVC use, the primary problems are due to malfunction (‘poor flows') or infection. Catheter malfunction leads to inadequate dialysis, the need for costly and inconvenient intervention, and reduced quality of life. This review will focus on the etiology, prevention, and management of CVC-related malfunction.

Aims: This study was designed to evaluate the extent of vancomycin removal from the blood compartment during sustained low-efficiency dialysis (SLED) and the efficacy of our current vancomycin dosing practice. Material: 10 ICU patients were selected. They all had oliguric renal failure requiring SLED and were on vancomycin therapy. SLED was provided with the Fresenius 2000K machine and used an AV400 polysulfone dialyzer (sieving coefficient for vitamin B 12 = 1, and surface area = 0.7 m 2 ). Method: SLED prescriptions were individualized for each patient but the duration for all was at least 8 hours. The blood flow rate (Qb) and dialysate flow rate (Qd) did not vary between patients by greater than 100 cc per minute. Blood samples were drawn at 0, 2, 4, and 8 hours to determine the extent of reduction in vancomycin level. Results: The total reduction of vancomycin was about 36% with an 8-hour treatment, when following a typical SLED prescription. Serum vancomycin levels dropped below the therapeutic window (< 15 mcg/ml) at the end of an 8-hour SLED session in almost half of the patients. Drug removal was greatest during the first 4 hours (29.5 ± 6.5%) compared to the last 4 hours (9.1 ± 7.4%) of SLED. Conclusions: Vancomycin removal during a typical 8-hour SLED treatment approaches 36%. SLED patients are at risk for undertreatment of their infections. A redosing strategy should be considered if the estimated or measured predialysis level is 20 - 30 mcg/ml. Vancomycin should be redosed with at least 500 mg in most patients at the completion of the SLED. Therapeutic drug monitoring (TDM) is an essential part of any dosing scheme, until further studies are done.

Purpose To determine the association between the initial hemodialysis (HD) vascular access type and short-term changes in inflammation markers. Methods This is a prospective, observational study in incident chronic kidney disease (CKD) (stages 4 and 5) patients receiving their first HD vascular access. Serum samples were obtained pre-access placement, and 1 week, and 1 month post-access insertion. Samples were tested for high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) using ELISA. Patients with known inflammatory states (infection, malignancy, connective tissue disorders, organ transplantation and those on immune modulating agents) were excluded. The hsCRP and IL-6 values were transformed into logarithmic scale. Chi-square analysis, independent and paired t-tests were performed where appropriate, and a two-way ANOVA with time as a repeated measure was also performed. Significance was determined at p=0.05. Results One-month follow-up data was obtained in 48 patients (arteriovenous fistula (AVF), n=10; tunneled catheter (TC), n=28; arteriovenous graft (AVG), n=10). A significant increase in both hsCRP (pConclusions In CKD patients, TC and AVG insertion result in a transient state of inflammation 1 week post-operatively, which is not observed after AVF surgery. Whether this is a persistent phenomenon after TC insertion requires a larger, longitudinal study.

The increased burden of chronic kidney and end-stage kidney diseases (ESKD) in populations of African ancestry has been largely unexplained. To identify genetic variants predisposing to idiopathic and HIV-1–associated focal segmental glomerulosclerosis (FSGS), we carried out an admixture-mapping linkage-disequilibrium genome scan on 190 African American individuals with FSGS and 222 controls. We identified a chromosome 22 region with a genome-wide logarithm of the odds (lod) score of 9.2 and a peak lod of 12.4 centered on MYH9, a functional candidate gene expressed in kidney podocytes. Multiple MYH9 SNPs and haplotypes were recessively associated with FSGS, most strongly a haplotype spanning exons 14 through 23 (OR ¼ 5.0, 95% CI ¼ 3.5–7.1; P ¼ 4 � 10 � 23 , n ¼ 852). This association extended to hypertensive ESKD (OR ¼ 2.2, 95% CI ¼ 1.5–3.4; n ¼ 433), but not type 2 diabetic ESKD (n ¼ 476). Genetic variation at the MYH9 locus substantially explains the increased burden of FSGS and hypertensive ESKD among African Americans.

The management of tunneled cuffed catheter (TCC)-associated bacteremias varies among nephrologists. To determine whether patient outcomes after TCC-associated bacteremia can be improved by modifying the management model, we performed an interventional controlled trial comparing a collaborative team model, intervention (INT), with the usual physician-managed model, usual care (UC).INT consisted of an infection manager who worked closely with nephrologists and dialysis staff and made treatment recommendations using the available published guidelines at the time of the study's conception (Dialysis Outcomes Quality Initiative guideline no. 26, 1997) and additional literature-based recommendations. Nephrologists made the final treatment decisions. TCC-associated bacteremia was physician managed in the UC group.Two hundred twenty-three episodes of TCC-associated bacteremia occurred in 7 outpatient hemodialysis units during the 2-year study period. The INT was associated with a significantly lower incidence of recurrent bacteremia with the same organism (INT, 6% versus UC, 18%; odds ratio, 0.28; 95% confidence interval, 0.09 to 0.8; P = 0.015) and death from sepsis (INT, 0% versus UC, 6%; P0.02). In INT units, there was a 45% decrease in the practice of TCC salvage (TCC not removed; P = 0.05). Antibiotic prescribing practices (final antibiotic selection, dose, and duration of therapy) were improved in INT units compared with UC units. By using multivariate analysis, the INT was associated with a 73% decrease in the combined outcome of recurrent bacteremia or septic death (P0.02).Implementation of a collaborative team model for the management of TCC-associated bacteremic episodes is associated with improvement in the quality of heath care delivery and patient outcomes.

Background. Infection is a serious complication of tunnelled cuffed catheter (TCC) use and is associated with high complication and mortality rates. Although attempts at TCC salvage after bacteraemia have been associated with high rates of recurrent bacteraemia, there have been no large studies in which multivariate analysis has been performed to control for confounding factors such as infecting organisms, diabetes, etc. Methods. A prospective observational study was performed in chronic HD patients dialyzing with a TCC at seven outpatient HD centers. All patients diagnosed with TCC bacteraemia were observed for 3 months following initial presentation and outcomes were recorded. Results. During the 2.5 year study period, 226 patients had an episode of TCC bacteraemia that met inclusion criteria, and 3 month follow-up data were available in 219 episodes. Treatment failure, defined as recurrent TCC bacteraemia with the same organism or death from sepsis, occurred in 26 patients (12%). Infectious complications (such as endocarditis, osteomyelitis, etc.) occurred in 16 patients (7%), bacteraemia with a different organism occurred in 19 patients (9%), and death from sepsis occurred in eight patients (4%). Significant predictors of treatment failure (by univariate analysis) were TCC salvage, and infection with Staphylococcus aureus, (OR ¼ 4.2, P ¼ 0.002; and OR ¼ 3.3, P ¼ 0.02, respectively). TCC salvage, when used in episodes of S. aureus bacteraemia, was associated with an 8-fold higher risk of treatment failure (P ¼ 0.001). The presence of an abnormal TCC exit site was associated with a significantly higher rate of death from sepsis, (OR ¼ 7, P ¼ 0.001). Outcomes (treatment failure and infectious complications) did not differ among bacteraemic episodes where the TCC was exchanged over a guidewire compared to those in which the TCC was immediately removed followed by delayed reinsertion. In the multivariate analysis, adjusted for potential confounding covariates, the only significant predictors of treatment failure after an episode of TCC bacteraemia were TCC salvage (OR ¼ 5.4, P ¼ 0.003), and S. aureus (OR ¼ 4.2, P ¼ 0.002). In a multivariate analysis, controlling for TCC management, the only variable that was significantly associated with the development of an infectious complication was infection with S. aureus (OR ¼ 3.5, P ¼ 0.02). Conclusions. We have shown, using multivariate analysis and adjusting for potential confounding factors, that the use of TCC salvage and S. aureus are independent risk factors for treatment failure after an episode of TCC bacteraemia, and that S. aureus is an independent risk factor for developing an infectious complication. An infected-appearing TCC exit site is associated with a higher mortality rate. Episodes of TCC bacteraemia treated using TCC salvage are associated with the highest treatment failure rates. TCC guidewire exchange can be an acceptable practice, unless severe exit site or tunnel infection is present.

Background. Pseudomonas is regarded as a particularly lethal bacterial isolate. High mortality rates have been reported in episodes of Pseudomonas sepsis when associated with visceral infections as seen in immuno-suppressed, hospitalized patients. In comparison, lower mortality rates have been reported with catheter-associated Pseudomonas bacteraemia in non-dialysis patients. The purpose of this study was to determine the risk factors and the outcomes for episodes of Pseudomonas bacteraemia associated with the use of tunnelled cuffed haemodialysis catheters (TCCs) in a chronic out-patient population. Methods. We performed a prospective observational study in seven chronic haemodialysis units over a 2.5 year period. Patients who were diagnosed as having their initial TCC-associated bacteraemia within the study period were followed for 3 months. All episodes of Pseudomonas TCC bacteraemia were identified, and univariate analyses were performed to compare Pseudomonas bacteraemia with non-Pseydinibas bacteraemia. Results. During the study period, 219 episodes of TCC bacteraemia were identified; 18 had a Pseudomonas isolate (8%). Pseudomonas bacteraemia episodes were associated with a significantly higher risk of not receiving appropriate initial antibiotics (odds ratio = 3.6, P=0.02). There were no deaths in the Pseudomonas bacteraemia group, whereas 19% died in the non-Pseudomonas group. The TCC was removed in 89% of Pseudomonas bacteraemias. There were no significant risk factors for acquiring a Pseudomonas isolate, and no difference in recurrent bacteraemia or infectious complication rates between the groups. Conclusions. In haemodialysis patients with a TCC-associated Pseudomonas bacteraemia, outcomes are remarkably good. This may be because the source of Pseudomonas infection was removed in most cases. Initial antibiotic coverage lacking anti-Pseudomonas activity was not associated with increased mortality.

We report the identification of a novel Wilms tumor suppressor gene mutation in a 5-month-old girl who presented with unilateral Wilms tumor (WT) and renal diffuse mesangial sclerosis typical of Denys-Drash syndrome (DDS). The patient did not have ambiguous genitalia and the karyotype (by amniocentesis) was 46, XX. A de novo constitutional heterozygous mutation in WT1 gene exon 9 coding for the third zinc-finger (1163G--A, C388Y) was identified. This mutation affects a cysteine residue involved in the coordination of the zinc atom, confirming the importance of these residues in the biological function of WT1 protein.

Infection rates in tunneled-cuffed catheters (TCC) are reported to be higher in immunocompromised patients. The purpose of this study was to evaluate TCC-associated infection rates in patients with HIV infection (HIV+). Data were collected in 40 HIV + patients and 41 controls (C), and in 118 TCC (HIV+, 58; C, 60) for 28,146 catheter days (HIV+, 16,227; C, 11,919). There were no significant differences in the TCC bacteremia rates (HIV+, 2.23 versus C, 2.53 per 1000 TCC days, P: = NS) or in the TCC exit site infection rates (HIV+, 2.20 versus C, 2.24 per 1000 TCC days, P: = NS) between the groups. The number of TCC removed due to infection was also similar, (HIV+ versus C: 17 versus 15%, P: = NS). In the HIV+ group, the association of hepatitis B surface antigenemia with TCC exit site infection was dependent on the history of injection drug use. Black race was a significant risk factor for higher TCC exit site infection rates, whereas prophylactic antibiotic use and high CD4 count were significantly associated with lower TCC exit site infection rates. None of the factors significantly predicted bacteremia rate in either group (HIV+ or C). In comparison to controls, HIV+ patients had a fivefold increased risk of having a Gramnegative organism (P: = 0.02) and a sevenfold increased risk of a fungal isolate (P: = 0.08), although the latter finding was not statistically significant. HIV infection is not a significant risk factor for TCC-associated infection but is associated with a higher prevalence of Gram-negative and fungal species.

Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies. Background Mature podocytes are growth-arrested because of the expression of cyclin-dependent kinase inhibitors. Under pathological conditions, podocytes may undergo mitosis, but not cell division. Exceptions to this rule are collapsing glomerulopathies (CGs), including HIV-associated nephropathy (HIVAN) and idiopathic CG, where podocytes undergo a dysregulation of their differentiated phenotype and proliferate. Methods To shed light on the mechanism underlying podocyte proliferation in CG, we analyzed the expression of the proliferation marker Ki-67, cyclins (A, D1), cyclin-dependent kinase inhibitors (p27, p57), and podocyte differentiation marker synaptopodin in eight cases of HIVAN and two cases of idiopathic CG. Normal fetal and adult kidneys served as controls. Results Both HIVAN and idiopathic CG showed a marked reduction in the expression of p27, p57, and cyclin D1 (absent in 69, 62, and 80% of all glomeruli, respectively). Cyclin A and Ki-67 were expressed in 11 and 29% of all glomeruli. Moreover, there was partial loss of synaptopodin and cyclin D1 expression in nonaffected glomeruli. Conclusions The loss of p27 and p57 leading to expression of cyclin A may account for the activation of podocyte proliferation in CG. Furthermore, the loss of cyclin D1 from histologically normal glomeruli suggests a possible role of cyclin D1 in mediating the dysregulation of the podocyte cell cycle in CG. These novel findings offer insight into the molecular regulation of mature podocyte differentiation. Podocyte proliferation in CG provides evidence in support of a previously underestimated plasticity of mature podocytes.

Life-threatening digoxin toxicity may be effectively treated with digoxin-specific antibody fragments (Fab). However, in end-stage renal disease, the digoxin-Fab complexes persist in the circulation and dissociate, potentially resulting in rebounding free digoxin levels and the recurrence of symptomatic toxicity. To prevent this rebound phenomenon, plasma exchange (PE) has been implemented for the removal of the digoxin-Fab complexes in renal failure. However, there is only one case report describing its use in this setting. To better determine the optimal timing of PE after Fab administration, we performed two PE treatments (each preceded by Fab) in a patient with acute renal failure and acute digoxin poisoning. The admission serum digoxin level was 21 ng/mL. The timing of the PE treatments relative to Fab dosing was as follows: the first PE was performed 26 hours post-Fab, and the second PE was performed 2.5 hours post-Fab. The plasma ultrafiltrate digoxin concentration was 2.5-fold greater when PE was performed 2.5 hours versus 26 hours after Fab administration (19.9 versus 8.1 ng/mL). The combined total amount of digoxin removed in the ultrafiltrate plasma was minimal (0.13 mg), less than 1% of the total amount of ingested drug. We conclude that the optimal timing of PE is within the first 3 hours after Fab administration. Although PE is efficacious for removing digoxin-Fab complexes, thus preventing rebound digoxin toxicity, it is not efficacious for improving total digoxin clearance because of the large apparent volume of distribution of digoxin (5 to 8 L/kg).

Reports of human immunodeficiency virus-associated nephropathy (HIVAN) occurring in Hispanics, females and heterosexuals are scarce. We reviewed 858 charts from our total HIV population to determine the prevalence and epidemiology of HIVAN at our center, and to evaluate the renal and patient survival among individual groups, according to race, sex and HIV risk factor. The prevalence of HIVAN was low (1.9%), relative to other centers (4–13%). Although Hispanics accounted for 56% of the HIV population, only 38% of HIVAN patients were Hispanic. The absolute risk of HIVAN in blacks was 3.6%, and in Hispanics was 1.3%. The relative risk of blacks vs. Hispanics was 2.8% (p < 0.04). Women and men were represented equally in both the HIVAN and HIV populations. The mean (± SE) rate of decline in glomerular filtration rate was 3.7 ± 0.9 ml/min/month, and patient survival following the onset of HIVAN was 23.6 ± 4.8 months. We found no difference in renal or patient survival between individual groups. In summary, the risk of HIVAN in Hispanics is similar to that for whites. Male sex is not an independent risk factor. Both renal and patient survival are similar in blacks and Hispanics, and in men compared to women.

Understanding healthcare providers' preferences, values, and beliefs around AVF eligibility is important to explain variability in practice. We conducted a survey of international surgeons, using hypothetical patient scenarios, to assess resources used, variables, perceived barriers, and absolute contraindications to access creation. A total of 134 surgeons completed the survey. Venous duplex ultrasound mapping (VDUM) was offered to all patients by 90% of US, 68% Canadian, and 63% European respondents. VDUM altered clinical decision less than 25% of the time for 33% American, 48% Canadian, and 85% European surgeons. Increased comorbidities and previous failed access were deterrents to AVF creation as was vessel size. Second choice access was the AV graft in the US and Europe and the catheter in Canada. Absolute contraindications to AVF creation included patient life expectancy1 year, left ventricular ejection fraction (LVEF)15%, and a history of dementia, while 42% surgeons reported no absolute contraindications. Perceived barriers included patient preferences, long wait times for surgery, and late referral to a Nephrologist. Significant variability exists in the surgical preoperative assessment of patients, and the eligibility criteria used for fistula creation. Understanding surgeons' preferences can aid in establishing standardization for VA access eligibility, including surgical assessment.

Continuous renal replacement therapy (CRRT) has become a popular treatment modality but may have the disadvantage of producing substantial protein losses. With use of the Biuret method, a relatively insensitive assay, dialysate/ultrafiltrate protein losses have been reported to be as high as 1.3 g/L. With CRRT outputs of up to 50 L/day, these values would amount to protein losses of up to 65 g/day. In this study, dialysate/ultrafiltrate protein losses were reanalyzed by using a highly sensitive microprotein reagent (pyrogallol red) considered to be more accurate than previously available methods. Twenty-two dialysate/ultrafiltrate samples were obtained from Amicon-20 Diafilters or Fresenius F-80 dialyzers during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis/hemodiafiltration (CVVHD/F). Mean hourly output for all treatments was 1637 +/- 694 mL/h. Mean protein concentration for all 22 dialysate/ultrafiltrate samples was 4.2 +/- 4.0 mg/dL. Mean dialysate/ultrafiltrate protein concentrations were similar for the Amicon 20 (3.4 +/- 4.4 mg/dL, N = 9) and the Fresenius F-80 (4.7 +/- 3.9 mg/dL, N = 13) (P = not significant). Protein losses were higher during convection-based CVVH (6.0 +/- 5.1 mg/dL, N = 10; range, 1 to 15 mg/dL) than during the mixed convection and diffusion-based CVVHD/F (2.7 +/- 1.9 mg/dL, N = 12; range, 0 to 6 mg/dL) (P = 0.049). Mean serum protein concentration at the time of dialysate/ultrafiltrate sampling was 4.7 +/- 1.8 g/dL. There was a weak, but statistically significant correlation between the dialysate/ultrafiltrate samples and the corresponding value for serum protein (r = 0.468, P < 0.03). It was concluded that protein losses during CRRT treatments are substantially lower than previously reported, are dependent on the serum protein concentration and the predominant nature of solute removal (convection versus diffusion), and can vary between 1.2 and 7.5 g/day.

This review addresses the types of vascular access available for patients who need therapeutic apheresis (TA). As in hemodialysis, vascular access for TA is chosen based on type of procedure prescribed, the patient's vascular anatomy, the acuity, frequency and duration of treatment, and the underlying disease state. The types of access available include peripheral vein cannulation, central venous catheters: including nontunneled and tunneled catheters, arterio-venous grafts and arterio-venous fistulas. Peripheral veins and central venous catheters are most frequently utilized for the acute administration of TA, and may be used over a period of weeks to months. Arterio-venous grafts and fistulas are not commonly used in TA procedures, but are an option in patients with an anticipated long course of TA, usually for a period of several months or years. The types and frequency of complications associated with various types of vascular access, including: access dysfunction and infections are reviewed, and strategies for their prevention and management are offered.

The maintenance of tunneled catheter (TC) patency is critical for the provision of adequate hemodialysis in patients who are TC-dependent. TC dysfunction results in the need for costly and inconvenient interventions, and reduced quality of life. Since the introduction of TCs in the late 1980s, heparin catheter lock has been the standard prophylactic regimen for the prevention of TC dysfunction. More recently, alternative catheter locking agents have emerged, and in some cases have shown to be superior to heparin lock with respect to improving TC patency and reducing TC-associated infections. These include citrate, tissue plasminogen activator, and a novel agent containing sodium citrate, methylene blue, methylparaben, and propylparaben. In addition, prophylaxis using oral anticoagulants/antiplatelet agents, including warfarin, aspirin, ticlodipine, as well as the use of modified heparin-coated catheters have also been studied for the prevention of TC dysfunction with variable results. The use of oral anticoagulants and/or antiplatelet agents as primary or secondary prevention of TC dysfunction must be weighed against their potential adverse effects, and should be individualized for each patient.

Therapeutic plasma exchange is a treatment modality used in a variety of disease states, some of which are characterized by renal involvement (ie, Goodpasture's syndrome, multiple myeloma, cryoglobulinemia, and thrombotic thrombocytopenic purpura). To investigate the safety of this procedure we evaluated all patients receiving plasma-pheresis at the University of Connecticut from January 1988 to June 1991. Sixty-eight adverse reactions occurred in 699 treatments, resulting in an incidence of 9.7%. The most frequent complications were symptoms of hypocalcemia, hypovolemia, and anaphylactoid reactions. The incidence of hypocalcemic symptoms was lowered with the prophylactic administration of calcium. Without calcium prophylaxis the incidence of symptoms was 9.1% (six in 66 treatments), whereas with calcium prophylaxis the incidence was reduced to 1% (six in 633 treatments) (P < 0.01). Treatments in which albumin was administered as volume replacement were associated with fewer adverse reactions when compared with those using fresh-frozen plasma (1.4% v 20%). Our experience, combined with the 15,658 procedures reported in the literature, reveals that serious complications do not commonly occur. These are characterized by cardiovascular events (0.2%), respiratory events (0.2%), and anaphylactoid reactions (0.25%). Hemorrhage and infection are rare, each occurring at a rate of 0.02%. Death was reported in eight of 15,658 procedures (0.05%). We conclude that therapeutic plasma exchange is relatively safe and alterations in plasma proteins generally are well tolerated. Prophylactic calcium administration lowers the incidence of hypocalcemic symptoms. Adverse reactions are associated more commonly with the administration of fresh-frozen plasma.

Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown. Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN. The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly. These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice.

Background. The contribution of the hemodialysis (HD) vascular access type to inflammation is unclear. Methods. We conducted a prospective observational study in an incident HD population. C-reactive protein (CRP), interleukin-6 (IL-6), and interferon-γ-induced protein (IP-10) were measured before and at 6-time points after access placement for 1 year. Results. Sixty-four incident HD patients were included (tunneled catheter (TC), 𝑛 = 4 0 , arteriovenous fistula (AVF), 𝑛 = 1 4 , and arteriovenous graft (AVG), 𝑛 = 1 0 ). A mixed effects model was performed to adjust for age, sex, race, coronary artery disease, diabetes mellitus, infections, access thrombosis, initiation of HD, and days after access surgery. In comparison to AVFs, the presence of a TC was associated with significantly higher levels of CRP ( 𝑃 = 0 . 0 3 ), IL-6 ( 𝑃 = 0 . 0 7 ), and IP-10 ( 𝑃 = 0 . 0 3 ). The presence of an AVG was associated with increases in CRP ( 𝑃 = 0 . 0 1 ) and IP-10 ( 𝑃 = 0 . 0 7 ). Conclusions. Patients who initiate HD with a TC or an AVG have a heightened state of inflammation, which may contribute to the excess 90-day mortality after HD initiation.

Chidi Okafor, David M. Ward, Michele H. Mokrzycki, Robert Weinstein, Pamela Clark, and Rasheed A. Balogun* Department of Medicine, Division of Nephrology, University of Virginia Health System, Charlottesville, Virginia Department of Medicine, University of California, San Diego, California Department of Medicine, Albert Einstein College of Medicine, Bronx, New York Departments of Medicine and Pathology, University of Massachusetts, Amherst, Massachusetts Department of Pathology, University of Virginia, Charlottesville, Virginia

Background. There is marked variation in the use of the arteriovenous fistula (AVF) across programmes, regions and countries not explained by differences in patient demographics or comorbidities. The lack of clear criteria of who should or should not get a fistula may contribute to this, as well as barriers to creating AVFs. Methods. We conducted a survey of Canadian and American nephrologists to assess the patient variables considered to determine the timing and type of access requested. Perceived barriers and absolute contraindications to access were also collected. Results. An immediate referral for a fistula was more highly preferred when patients are

Renal parenchymal malacoplakia is a rare cause of renal failure. Patients presenting with renal failure carry a poor prognosis, the majority either dying or requiring chronic dialysis. In this report, we describe an alcoholic man who presented with renal failure due to bilateral renal parenchymal malacoplakia and papillary necrosis. The patient, who initially required dialysis, partially recovered renal function following prolonged antibiotic treatment with a fluoroquinolone antibiotic.

This Practice Point commentary discusses the findings and limitations of a meta-analysis that evaluated the use of prophylactic antibiotics for hemodialysis catheters. Use of prophylactic topical antibiotics at the catheter exit site was associated with a significant reduction in catheter-related bacteremia, exit-site infections, catheter removals due to secondary complications, hospitalizations for infection, and patient mortality. Use of prophylactic intraluminal antibiotic instillation was associated with a significantly reduced risk of catheter-related bacteremia and need for catheter removal. This commentary highlights the issues that should be considered when interpreting and generalizing these results, including the variability of antibiotic type and catheter type (nontunneled vs tunneled), the use of co-interventions in the various trials, and potential publication bias. The known benefits of prophylactic antibiotic use in patients with hemodialysis catheters are strongly supported by this meta-analysis.

Wilms’ tumor gene ( WT1) is important for nephrogenesis and gonadal growth. WT1 mutations cause Denys-Drash and Frasier syndromes, which are characterized by glomerular scarring. To test whether genetic variations in WT1 and WIT1 (gene immediately 5′ to WT1) associate with focal segmental glomerulosclerosis (FSGS), patients with biopsy-proven idiopathic and HIV-1-associated FSGS were enrolled in a multicenter study. We genotyped SNP rs6508 located in WIT1 exon 1, three SNPs (rs2301250, rs2301252, rs2301254) in the promoter shared by WT1 and WIT1, rs2234590 in exon 6, rs2234591 in intron 6, rs16754 in exon 7, and rs1799937 in intron 9 of WT1. Cases ( n = 218) and controls ( n = 281) were compared in the African American population. Stratification by HIV-1 infection status showed that SNPs rs6508, rs2301254, and rs1799937 were significantly associated with FSGS [rs6508 odds ratio (OR) 1.82, P = 0.006; rs2301254 OR 1.65, P = 0.049; rs1799937 OR 1.91, P = 0.005] in the non-HIV-1 group and rs2234591 (OR 0.234, P = 0.011) in the HIV-1 group. Haplotype analyses in the population revealed that seven SNPs were associated with FSGS; five SNPs had the highest contingency score [−log10( P value) = 13.57] in the HIV-1 group. This association could not be explained by population substructure. We conclude that SNPs in WT1 and WIT1 genes are significantly associated with FSGS, suggesting that variants in these genes may mediate pathogenesis by altering WT1 function. Furthermore, HIV-1 infection status interacts with genetic variations in both genes to influence this phenotype. We speculate that nephropathy liability alleles in WT1 pathway genes cause podocyte dysfunction and glomerular scarring.

Aims: In the existing literature, there is a paucity of data regarding large atrial thrombus (AT) formation occurring as a complication of tunneled cuffed hemodialysis catheter (TCC) use. This study was performed to determine the risk factors, mortality and the appropriate management of TCC-AT. Methods: We report 6 new cases of TCC-AT and have amalgamated these data with data from 16 previously published cases of TCC-AT found by performing a PubMed literature search (total of 22 cases). Demographic data were collected prospectively over 2 years in 85 consecutive patients initiating hemodialysis who were using a TCC as their primary vascular access, so that comparisons could be made between the 6 patients with TCC-AT versus all patients with a TCC at our center. Results: In patients with TCC-AT, the mean time from TCC insertion was 4.5 months, and infection was present at the time of diagnosis in 68% of cases. The mean thrombus size was 3.7 cm, range 1.5 - 8 cm. All but 1case were visualized by echocardiography; the remaining case required magnetic resonance imaging. Management included TCC removal and thrombectomy (n = 9), TCC removal and anticoagulation (AC) (n = 6), TCC removal alone (n = 5), and no intervention (n = 2). The overall mortality was 27%, and 5 of the 6 deaths (83%) occurred in patients with bacteremia. The mortality associated with each management strategy was as follows: TCC removal and thrombectomy (0%), TCC removal and AC (33%), TCC removal alone (40%), and no intervention (100%). Conclusions: AT is a serious complication of TCC use in hemodialysis patients and may be associated with a high mortality rate. TCC-AT may occur more commonly than previously reported and therefore warrants a high index of suspicion.