Serial SARS-CoV-2 Antibody Titers in Vaccinated Dialysis Patients: Prevalence of Unrecognized Infection and Duration of Seroresponse.

Rationale & Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are likely underdiagnosed, but the degree of underdiagnosis among patients receiving maintenance dialysis is unknown. The durability of the immune response after the third vaccine dose in this population also remains uncertain. This descriptive study tracked antibody levels to (1) assess the rate of undiagnosed infections and (2) characterize seroresponse durability after the third dose. Study Design: Retrospective observational study. Setting & Participants: SARS-CoV-2-vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies [anti-spike immunoglobulin (Ig) G] titers were assessed monthly after vaccination. Exposures: Two and 3 doses of SARS-CoV-2 vaccine. Outcomes: Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time. Analytical Approach: Undiagnosed SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥100 BAU/mL, not associated with receipt of vaccine or diagnosed SARS-CoV-2 infection (by polymerase chain reaction test or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2,703 patients without previous coronavirus disease 2019 (COVID-19) who received an initial 2-dose vaccine series, 271 had diagnosed SARS-CoV-2 infections (3.4 per 10,000 patient-days) and 129 had undiagnosed SARS-CoV-2 infections (1.6 per 10,000 patient-days). Among 1,894 patients without previous COVID-19 who received a third vaccine dose, 316 had diagnosed SARS-CoV-2 infections (7.0 per 10,000 patient-days) and 173 had undiagnosed SARS-CoV-2 infections (3.8 per 10,000 patient-days). In both cohorts, anti-spike IgG levels declined over time. Of the initial 2-dose cohort, 66% had a titer of ≥500 BAU/mL in the first month, with 24% maintaining a titer of ≥500 BAU/mL at 6 months. Of the third dose cohort, 95% had a titer of ≥500 BAU/mL in the first month after the third dose, with 77% maintaining a titer of ≥500 BAU/mL at 6 months. Limitations: The assays used had upper limits. Conclusions: Among patients receiving maintenance dialysis, about 1 in every 3 SARS-CoV-2 infections was undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A 3-dose primary mRNA vaccine series optimizes seroresponse rate and durability. Plain-Language Summary: Patients receiving maintenance dialysis have been particularly vulnerable to COVID-19. Using serially measured antibodies, we found that a substantial proportion (about one-third) of SARS-CoV-2 infections among this population had been missed, both among those who had completed a 2-dose vaccine series and among those who had received a third vaccine dose. Such missed infections likely had only mild or minimal symptoms, but this failure to recognize all infections is concerning. Furthermore, vaccines have been effective among patients receiving dialysis, but our study additionally shows that the immune response wanes over time, even after a third dose. There is therefore a role for ongoing vigilance against this highly transmissible infection.

Serial SARS-CoV-2 antibody titers in vaccinated dialysis patients: prevalence of unrecognized infection and duration of seroresponse.

Rationale & Objective: SARS-CoV-2 infections are likely underdiagnosed, but the degree of underdiagnosis among maintenance dialysis patients is unknown. Durability of the immune response after third vaccine doses in this population also remains uncertain. This study tracked antibody levels to 1) assess the rate of undiagnosed infections and 2) characterize seroresponse durability after third doses. Study Design: Retrospective observational study. Setting & Participants: SARS-CoV-2 vaccinated patients receiving maintenance dialysis through a national dialysis provider. Immunoglobulin G spike antibodies (anti-spike IgG) titers were assessed monthly following vaccination. Exposures: Two and three doses of SARS-CoV-2 vaccine. Outcomes: Undiagnosed and diagnosed SARS-CoV-2 infections; anti-spike IgG titers over time. Analytical Approach: "Undiagnosed" SARS-CoV-2 infections were identified as an increase in anti-spike IgG titer of ≥ 100 BAU/mL, not associated with receipt of vaccine or "diagnosed" SARS-CoV-2 infection (by PCR or antigen test). In descriptive analyses, anti-spike IgG titers were followed over time. Results: Among 2660 patients without prior COVID-19 who received an initial two-dose vaccine series, 371 (76%) SARS-CoV-2 infections were diagnosed and 115 (24%) were undiagnosed. Among 1717 patients without prior COVID-19 who received a third vaccine dose, 155 (80%) SARS-CoV-2 infections were diagnosed and 39 (20%) were undiagnosed. In both cohorts, anti-spike IgG levels declined over time. Of the initial two-dose cohort, 66% had a titer ≥ 500 BAU/mL in the first month, with 23% maintaining a titer ≥ 500 BAU/mL at six months. Of the third dose cohort, 95% had a titer ≥ 500 BAU/mL in the first month after the third dose, with 76% maintaining a titer ≥ 500 BAU/mL at six months. Limitations: Assays used had upper limits. Conclusions: Among maintenance dialysis patients, 20-24% of SARS-CoV-2 infections were undiagnosed. Given this population's vulnerability to COVID-19, ongoing infection control measures are needed. A three-dose primary mRNA vaccine series optimizes seroresponse rate and durability.

Seroresponse to SARS-CoV-2 Vaccines among Maintenance Dialysis Patients over 6 Months.

BACKGROUND AND OBJECTIVES: Although most patients receiving maintenance dialysis exhibit initial seroresponse to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, concerns exist regarding the durability of this antibody response. This study evaluated seroresponse over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included patients on maintenance dialysis, from a midsize national dialysis provider, who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. IgG spike antibodies (anti-spike IgG) titers were assessed monthly with routine laboratory tests after vaccination; the semiquantitative assay reported a range between zero and ≥20 Index. Descriptive analyses compared trends over time by history of coronavirus disease 2019 (COVID-19) and vaccine type. Time-to-event analyses examined the outcome of loss of seroresponse (anti-spike IgG <1 Index or development of COVID-19). Cox regression adjusted for additional clinical characteristics. RESULTS: Among 1870 patients receiving maintenance dialysis, 1569 had no prior COVID-19. Patients without prior COVID-19 had declining titers over time. Among 443 recipients of BNT162b2 (Pfizer), median (interquartile range) anti-spike IgG titer declined from ≥20 (5.89 to ≥20) in month 1 after full vaccination to 1.96 (0.60-5.88) by month 6. Among 778 recipients of mRNA-1273 (Moderna), anti-spike IgG titer declined from ≥20 (interquartile range, ≥20 to ≥20) in month 1 to 7.99 (2.61 to ≥20) by month 6. The 348 recipients of Ad26.COV2.S (Janssen) had a lower titer response than recipients of an mRNA vaccine over all time periods. In time-to-event analyses, recipients of Ad26.COV2.S and mRNA-1273 had the shortest and longest time to loss of seroresponse, respectively. The maximum titer reached in the first 2 months after full vaccination was associated with durability of the anti-spike IgG seroresponse; patients with anti-spike IgG titer 1-19.99 had a shorter time to loss of seroresponse compared with patients with anti-spike IgG titer ≥20 (hazard ratio, 15.5; 95% confidence interval, 11.7 to 20.7). CONCLUSIONS: Among patients receiving maintenance dialysis, vaccine-induced seroresponse wanes over time across vaccine types. Early titers after full vaccination are associated with the durability of seroresponse.

Catheter-directed thrombolytic infusion for thrombosed arteriovenous fistulas with a large clot burden: A case series.

Arteriovenous fistula (AVF) thrombosis occurs less often when compared to arteriovenous grafts. Since the number of AVFs has increased in the United States, AVF thrombosis is seen more frequently today. AVF thrombectomy can be tedious, requires physician ingenuity, and many times results in failure. Substantial clot burden in megafistulas and aneurysms is considered a relative contraindication to endovascular thrombectomy. Usually, it results in surgical referral for open thrombectomy or, at times, abandonment of the fistula altogether. Herein, we describe the technique, results, and cautions of combining a continuous infusion of recombinant tissue plasminogen (rTPA) followed by angioplasty of the culprit stenotic lesion that was successful in opening five of six AVFs with a substantial clot burden.

Nonuremic Calciphylaxis Associated With Hypercalcemia and Rheumatologic Diseases.

Calcific uremic arteriolopathy, termed calciphylaxis, was previously considered a condition that developed mostly in patients requiring dialysis. It has now been described in kidney transplant patients, in advanced chronic kidney disease (CKD) patients not requiring dialysis, and in individuals with maintained kidney function. We describe an individual with CKD stage 3b with hypercalcemia who presented with features highly specific for calciphylaxis based on results of a skin biopsy. The condition has high morbidity and mortality, and thus prompts immediate cessation of the offending agents or treatment of the cause. The following case and literature review demonstrates a need for a detailed assessment of patients' risks and exposures and expanding the differential diagnosis to include calciphylaxis in nonuremic patients with necrotic ulcers with a plan for early imaging and possible biopsy.

Associations between calf, thigh, and arm circumference and cardiovascular and all-cause mortality in NHANES 1999-2004.

BACKGROUND AND AIMS: Prior studies have described an association between calf circumference and cardiovascular disorders. We evaluated the associations between calf, thigh, and arm circumference and cardiovascular and all-cause mortality. METHODS AND RESULTS: We performed a retrospective cohort study of 11,871 patients in the 1999-2004 National Health and Nutrition Examination Survey (NHANES) to determine the association between calf circumference and cardiovascular and all-cause mortality using univariate and multivariate Cox proportional hazards. We additionally examined the association between thigh and arm circumference and mortality. In the multivariable Cox regression for the female stratum, each centimeter increase in calf circumference was associated with a hazard ratio of 0.88 (95% CI 0.84-0.92), and a hazard ratio of 0.90 (95% CI 0.85-0.95) for cardiovascular death. In the model with males, the hazard ratio for higher calf circumference was 0.92 (95% CI 0.88-0.96) for all-cause mortality and 0.94 (95% CI 0.89-0.99) for cardiovascular death. There was a statistically significant association between higher thigh circumference and lower risk of all-cause and cardiovascular mortality. Arm circumference was not similarly associated with mortality in the multivariate model. CONCLUSION: Calf and thigh circumference may provide important prognostic information regarding cardiovascular and all-cause mortality. Future prospective studies should examine the role of extremity circumference and cardiovascular events.

To ligate or not to ligate hemodialysis arteriovenous fistulas in kidney transplant patients.

There is significant disagreement about maintenance or ligation of arteriovenous fistulas (AVFs) in kidney transplant patients (KTPs). Potential harms from maintaining AVFs are their impact on cardiac function, cosmetic concerns and complications such as bleeding and rupture. High flow AVFs can place a strain on the heart and cause or exacerbate pre-existing cardiac dysfunction. There is an improvement in cardiac function after kidney transplantation independent of vascular access status. Studies comparing cardiac parameters in patients with and without AVFs after renal transplantation have shown conflicting results. Ligation of high flow AVFs in KTPs resulted in improvement in cardiac function and prevention of heart failure. In KTPs with deteriorating renal function and high flow AVFs, banding of the AVFs to reduce flow is an option. Patients who retain AVFs after renal transplant have the advantage of immediate, optimal access should the transplant fail and may have preserved kidney function. The patient's post-transplant kidney function, risk factors for transplant loss, AVF blood flow, and cardiac function play an important role when making the decision to ligate or preserve AVFs.

KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update.

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for hemodialysis vascular access since 1996. Since the last update in 2006, there has been a great accumulation of new evidence and sophistication in the guidelines process. The 2019 update to the KDOQI Clinical Practice Guideline for Vascular Access is a comprehensive document intended to assist multidisciplinary practitioners care for chronic kidney disease patients and their vascular access. New topics include the end-stage kidney disease "Life-Plan" and related concepts, guidance on vascular access choice, new targets for arteriovenous access (fistulas and grafts) and central venous catheters, management of specific complications, and renewed approaches to some older topics. Appraisal of the quality of the evidence was independently conducted by using a Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, and interpretation and application followed the GRADE Evidence to Decision frameworks. As applicable, each guideline statement is accompanied by rationale/background information, a detailed justification, monitoring and evaluation guidance, implementation considerations, special discussions, and recommendations for future research.

Perioperative acute kidney injury: Stratification and risk reduction strategies.

Perioperative acute kidney injury (AKI) is associated with increased morbidity and mortality. Patient comorbidities, the type of surgery, timing of surgery, and exposure to nephrotoxins are important contributors for developing acute kidney injury. Urgent or emergent surgery, cardiac, and organ transplantation procedures are associated with a higher risk of acute kidney injury. Nephrotoxic drugs, contrast dye, and diuretics can worsen preexisting kidney dysfunction or act as an additive and/or synergistic insult to perioperative injury. A history of preoperative chronic kidney disease is the main risk factor for developing AKI, conferring as much as a 10-fold risk. However, beyond the preoperative renal function, the development of AKI is a complex phenomenon that involves a combination of patient-related and surgery-related factors.

KDOQI Clinical Practice Guideline for vascular access: 2019 update

The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidencebased guidelines for hemodialysis vascular access since 1996. Since the last update in 2006, there has been a great accumulation of new evidence and sophistication in the guidelines process. The 2019 update to the KDOQI Clinical Practice Guideline for Vascular Access is a comprehensive document intended to assist multidisciplinary practitioners care for chronic kidney disease patients and their vascular access. New topics include the end-stage kidney disease "Life-Plan" and related concepts, guidance on vascular access choice, new targets for arteriovenous access (fistulas and grafts) and central venous catheters, management of specific complications, and renewed approaches to some older topics. Appraisal of the quality of the evidence was independently conducted by using a Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, and interpretation and application followed the GRADE Evidence to Decision frameworks. As applicable, each guideline statement is accompanied by rationale/background information, a detailed justification, monitoring and evaluation guidance, implementation considerations, special discussions, and recommendations for 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.

ASDIN white paper: Assessment and management of hemodialysis access-induced distal ischemia by interventional nephrologists.

Although not common, hemodialysis access-induced distal ischemia is a serious condition resulting in significant hemodialysis patient morbidity. Patients with signs and symptoms suggestive of hand ischemia frequently present to the general and interventional nephrologist for evaluation. In order to care for these cases, it is necessary to understand this syndrome and its management. Most cases can be managed conservatively without intervention. Some cases requiring intervention may be treated using techniques within the scope of practice of the interventional nephrologists while other cases require vascular surgery. In order for the interventional nephrologists to evaluate and manage these cases in a timely and appropriate manner, practice guidelines are presented.

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.

Patient selection, education, and cannulation of percutaneous arteriovenous fistulae: An ASDIN White Paper.

End-stage kidney disease patients who are candidates for surgical arteriovenous fistula creation commonly experience obstacles to a functional surgical arteriovenous fistula, including protracted wait time for creation, poor maturation, and surgical arteriovenous fistula dysfunction that can result in significant patient morbidity. The recent approval of two endovascular devices designed to create a percutaneous arteriovenous fistula enables arteriovenous fistula creation to be placed in the hands of interventionalists, thereby increasing the number of arteriovenous fistula providers, reducing wait times, and allowing the patient to avoid surgery. Moreover, current studies demonstrate that patients with percutaneous arteriovenous fistula experience improved time to arteriovenous fistula maturation. Yet, in order to realize the potential advantages of percutaneous arteriovenous fistula creation within our hemodialysis patient population, it is critical to select appropriate patients, ensure adequate patient and dialysis unit education, and provide sufficient instruction in percutaneous arteriovenous fistula cannulation and monitoring. In this White Paper by the American Society of Diagnostic and Interventional Nephrology, experts in interventional nephrology, surgery, and interventional radiology convened and provide recommendations on the aforementioned elements that are fundamental to a functional percutaneous arteriovenous fistula.

Physical examination of the hemodialysis arteriovenous fistula to detect early dysfunction.

The maintenance of vascular access patency for end-stage renal disease patients on hemodialysis is necessary for survival. Many nephrologists, nurse practitioners, and nurses have limited experience with the physical examination of the arteriovenous fistula. In this review, we define key terms used in the assessment of an arteriovenous fistula. We discuss the arteriovenous fistula physical exam, including details of inspection, palpation, and auscultation. Using these concepts, we review the abnormal findings that can assist practitioners in determining the location of a stenosis. We review the existing literature that validates physical exam findings with gold standard tests such as ultrasound and angiography. Finally, we review data supporting the value of training physicians and nurses in arteriovenous fistula physical examination.

Role of stents in hemodialysis vascular access.

Stents are ubiquitously utilized in coronary and peripheral arterial disease. Interventional nephrologists, however, place stents in the venous outflow of the arteriovenous access. Stenosis is the predominant pathology that causes access dysfunction and will ultimately lead to thrombosis if uncorrected. Angioplasty and stent deployment are the current techniques available to combat stenosis. From initial bare metal stainless steel stents, the current generations of stents used are predominately covered nitinol stents. The latest randomized control trials reveal that stents decrease the number of interventions required to maintain patency but do not improve the overall access survival. Furthermore, bare metal stents have been shown to be inferior to stent grafts. This review discusses indications for stent deployment in the hemodialysis access, the current evidence for their use, and briefly touches on their complications.