Author Correction: Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways.

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.

AKI in Hospitalized Patients with and without COVID-19: A Comparison Study.

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.

Understanding surgical preference and practice in hemodialysis vascular access creation.

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 <1 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.

Vascular access in therapeutic apheresis: update 2013.

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.

APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy.

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.

Prevention and management of catheter-related infection in hemodialysis patients.

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.

Standardized definitions for hemodialysis vascular access.

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.

Therapeutic apheresis: a review of complications and recommendations for prevention and management.

Therapeutic apheresis procedures are a form of extracorporeal therapy that use different techniques to separate blood into the different components out of which the part containing the etiological agent in a disease process is discarded and the rest of the components of blood are re-infused into the patient, frequently with the addition of a replacement fluid or volume. These complex procedures have inherent risks of adverse events and factors that may impact on the incidence these events include the underlying disease state, anticoagulation techniques, replacement fluid type including the volume, issues related to the vascular access used, and the therapeutic apheresis procedure type and technique. We present a representative case based review of common complications of therapeutic apheresis and suggestions about how to prevent or manage these as presented at the 2010 Therapeutic Apheresis Academy.

Implementation of an Electronic Catheter Checklist in Outpatient Hemodialysis Facilities: Results of a Pilot Quality Improvement Project.

Background: Performing catheter-care observations in outpatient hemodialysis facilities are one of the CDC's 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 CDC's 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.

Renal Considerations in COVID-19: Biology, Pathology, and Pathophysiology.

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.

Traditional and non-traditional strategies to optimize catheter function: go with more flow.

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. 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. 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.

Who should be referred for a fistula? A survey of nephrologists.

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 <65 years old, have minimal comorbidities or have no history of failed accesses. In older patients, and in those with increased comorbidities or a previously failed fistula, US nephrologists selected arteriovenous grafts as an alternative to the fistula, while Canadian nephrologists selected primarily catheters. Referral for vascular mapping was more common in the USA than in Canada. Gender did not influence the timing or the type of access. Perceived barriers to establishing a mature fistula included patient refusal for creation (77%) or cannulation (58%), delay in decision regarding dialysis modality (71%), wait time for surgical creation (55%) and high failure-to-mature rate (52%). We found that 27% of Canadian and 43% of American nephrologists indicated no absolute contraindications for permanent vascular access. CONCLUSIONS: This study demonstrated marked variability in timing and criteria used to select patients for referral for a vascular access between nephrologists practicing within Canada and the USA. Establishing minimal eligibility criteria for fistulae is an important area of future research.

Buttonhole Cannulation of Arteriovenous Fistulas in the United States.

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.

Chronic Hemodialysis Patients Hospitalized with COVID-19: Short-term Outcomes in the Bronx, New York.

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.

Prevention of Bloodstream Infections in Patients Undergoing Hemodialysis.

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.

The association of race and COVID-19 mortality.

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.

Vascular access type and changes in inflammatory markers in incident dialysis patients: a pilot study.

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 (p <0.05) and IL-6 (p=0.02) occurring 1 week after TC insertion was observed. Elevation of the IL-6 levels appeared to be sustained 1 month after TC insertion, although this finding was not statistically significant (p=0.68), whereas the hsCRP levels returned to baseline within 1 month. After AVG insertion only the hsCRP levels rose significantly (p=0.01) after 1 week and returned to baseline within 1 month. In the AVF group, inflammatory markers did not change for any time period. CONCLUSIONS: 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.

Use of prophylactic topical or intraluminal antibiotics for hemodialysis catheters.

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.