Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis.

In 2021, the Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases was published. KDIGO is committed to providing the nephrology community with periodic updates, based on new developments for each disease. For patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), avacopan received regulatory approval in late 2021, leading to this KDIGO guideline update. In addition, the evidence supporting a lower-dose glucocorticoid induction regimen or even complete replacement of glucocorticoids has become stronger. Herein, an executive summary of the most important guideline changes from the AAV chapter is provided as a quick reference.

Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases was published in 2021. Since then, the pace of drug development for glomerular diseases has accelerated, due in large part to rapidly accumulating insights into disease pathogenesis from genetic and molecular studies of afflicted patients. To keep the Glomerular Diseases Guideline as current as possible, KDIGO made a commitment to the nephrology community to provide periodic updates, based on new developments for each disease. After the 2021 guideline was published, two novel drugs received regulatory approval for the management of lupus nephritis, leading to the first KDIGO guideline update. Herein, an executive summary of the most important guideline changes from the Lupus Nephritis chapter is provided as a quick reference.

Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease: Synopsis of the Kidney Disease: Improving Global Outcomes 2022 Clinical Practice Guideline.

DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 clinical practice guideline on prevention, diagnosis, evaluation, and treatment of hepatitis C in chronic kidney disease (CKD) is an update of the 2018 guideline from KDIGO. METHODS: The KDIGO Work Group (WG) updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and used expert judgment to develop recommendations. New evidence led to updating of recommendations in the chapters on treatment of hepatitis C virus (HCV) infection in patients with CKD (Chapter 2), management of HCV infection before and after kidney transplant (Chapter 4), and diagnosis and management of kidney disease associated with HCV infection (Chapter 5). Recommendations in chapters on detection and evaluation of hepatitis C in CKD (Chapter 1) and prevention of HCV transmission in hemodialysis units (Chapter 3) were not updated because of an absence of significant new evidence. RECOMMENDATIONS: The 2022 updated guideline includes 43 graded recommendations and 20 ungraded recommendations, 7 of which are new or modified on the basis of the most recent evidence and consensus among the WG members. The updated guidelines recommend expanding treatment of hepatitis C with sofosbuvir-based regimens to patients with CKD glomerular filtration rate categories G4 and G5, including those receiving dialysis; expanding the donor pool for kidney transplant recipients by accepting HCV-positive kidneys regardless of the recipient's HCV status; and initiating direct-acting antiviral treatment of HCV-infected patients with clinical evidence of glomerulonephritis without requiring kidney biopsy. The update also addresses the use of immunosuppressive regimens in such patients.

Kidney Transplantation From Hepatitis C Virus-Infected Donors to Uninfected Recipients: A Systematic Review for the KDIGO 2022 Hepatitis C Clinical Practice Guideline Update.

RATIONALE & OBJECTIVE: Direct-acting antiviral (DAA) treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD) has made transplantation of kidneys from HCV-infected donors to uninfected recipients (D+/R-) feasible. To facilitate an update to the 2018 KDIGO guideline for patients with CKD and HCV, we conducted a systematic review of HCV D+/R-kidney transplantation coupled with DAA treatment. STUDY DESIGN: Systematic review and meta-analysis. SETTING & STUDY POPULATIONS: We included studies of HCV D+/R-kidney transplantations that used any DAA protocol. SELECTION CRITERIA FOR STUDIES: Based on a search of PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, conferences from 2019 to 2021, and the 2018 KDIGO HCV guideline we identified single-group (D+/R-) or comparative studies of D+/R-versus D-/R-kidney transplantation. DATA EXTRACTION: Conducted in SRDR-Plus with review by a second researcher. ANALYTICAL APPROACH: Maximum likelihood meta-analyses; the certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: We identified 16 studies (N=557). A sustained viral response at 12 weeks after treatment (SVR12) was observed in 97.7% (95% CI, 96.3%-98.8%). Ultrashort duration treatment (≤8 days) resulted in viremia requiring standard-course DAA treatment in some patients, all of whom achieved SVR12 after 1 or rarely 2 DAA courses. Serious adverse events from DAA treatment were rare after D+/R-transplantation (0.4% [95% CI, 0.1%-2.8%]). At≥1 year after D+/R-transplantation, recipient death occurred in 2.1% (95% CI, 0.9-3.7) and allograft survival was 97.6% (95% CI, 95.7%-98.9%). Estimated glomerular filtration rate 1 year after transplantation ranged from 46 to 74mL/min/1.73m2. LIMITATIONS: Analyses were generally based on low-certainty evidence. Uncertainty exists about the long-term safety and efficacy of D+/R-transplantation. Few studies investigated ultrashort treatment courses. CONCLUSIONS: Kidney transplantation from HCV-infected donors to uninfected recipients followed by DAA treatment appears to be safe and associated with excellent 1-year clinical outcomes. PLAIN-LANGUAGE SUMMARY: Due to the high efficacy of direct-acting antivirals (DAA), the use of kidneys from HCV-infected deceased donors may increase rates of kidney transplantation. We conducted a systematic review for the 2022 KDIGO Clinical Practice Guideline on Hepatitis C to evaluate the safety and efficacy of kidney transplantation from HCV-infected donors to uninfected recipients (D+/R-) followed by DAA therapy. Sixteen studies comprising 557 patients revealed high rates of sustained viral response, low rates of adverse events, and excellent patient and allograft survival 1 year after transplantation. Kidney transplantation from HCV-infected deceased donors to uninfected recipients treated with DAA appears safe and effective. Future studies should investigate shorter treatment durations, monitor safety, and obtain longer-term efficacy data.

A Systematic Review of Direct-Acting Antivirals for Hepatitis C in Advanced CKD.

Introduction: Direct-acting antivirals (DAAs) have improved treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD). To facilitate the 2022 update of the Kidney Disease: Improving Global Outcomes (KDIGO) guideline for CKD patients with HCV, we systematically reviewed DAA regimens in patients with CKD stages G4 and G5 nondialysis (G4-G5ND), CKD stage G5 on dialysis (G5D), and kidney transplant recipients (KTRs). Methods: We conducted a systematic review by searching PubMed, Embase, Cochrane, CINAHL, and ClinicalTrials.gov through February 1, 2022, and conferences from 2019 to 2021. Studies of HCV-infected patients with CKD G4-G5ND, G5D, and KTRs treated with specified DAA regimens were included. Outcomes included death at 6 months or later, sustained virologic response at 12 weeks (SVR12), serious adverse events (SAEs) attributed to DAA, and treatment discontinuation because of adverse events. Maximum likelihood meta-analyses were determined; certainty of evidence was assessed per GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Results: We identified 106 eligible studies (22 reported on CKD G4-G5ND, 69 on CKD G5D, and 29 on KTRs). In each population, the majority of DAA regimens achieved SVR12 ≥ 93%. We found generally low quality of evidence of low risk of SAEs (mostly 0%, up to 2.9%) and low risk of discontinuation because of adverse events (mostly 0%-5%). Across 3 unadjusted observational studies in KTRs, the risk of death after DAA treatment was substantially lower than without treatment (summary odds ratio, 0.16; 95% CI, 0.04-0.61). Conclusion: Combination DAA regimens are safe and highly effective in patients with advanced CKD, on dialysis, and with kidney transplants.

Executive Summary of the KDIGO 2022 Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in Chronic Kidney Disease.

Infection with the hepatitis C virus (HCV) has adverse liver, kidney, and cardiovascular consequences in patients with chronic kidney disease (CKD), including those on dialysis therapy or with a kidney transplant. Since the publication of the Kidney Disease: Improving Global Outcomes (KDIGO) HCV Guideline in 2018, advances in HCV management, particularly in the field of antiviral therapy and treatment of HCV-associated glomerular diseases, coupled with increased usage of HCV-positive kidney grafts, have prompted a reexamination of the 2018 guideline. As a result, the Work Group performed a comprehensive review and revised the 2018 guidance. This Executive Summary highlights key aspects of the updated guideline recommendations for 3 chapters: Chapter 2: Treatment of HCV infection in patients with CKD; Chapter 4: Management of HCV-infected patients before and after kidney transplantation; and Chapter 5: Diagnosis and management of kidney diseases associated with HCV infection.

Health care consequences of hospitalization with Clostrioides difficile infection: a propensity score matching study.

BACKGROUND: Clostridiodies difficile infection (CDI) has been characterized by the Center for Disease Control and Prevention (CDC) as an urgent public health threat and a major concern in hospital, outpatient and extended-care facilities worldwide. METHODS: A retrospective cohort study of patients aged ≥ 18 hospitalized with CDI in New York State (NYS) between January 1, 2014-December 31, 2016. Data were extracted from NY Statewide Planning and Research Cooperative (SPARCS) and propensity score matching was performed to achieve comparability of the CDI (exposure) and non-CDI (non-exposure) groups. Of the 3,714,486 hospitalizations, 28,874 incidence CDI cases were successfully matched to 28,874 non-exposures. RESULTS: The matched pairs comparison demonstrated that CDI cases were more likely to be readmitted to the hospital at 30 (28.26% vs. 19.46%), 60 (37.65% vs. 26.02%), 90 (42.93% vs. 30.43) and 120 days (46.47% vs. 33.74), had greater mortality rates at 7 (3.68% vs. 2.0%) and 180 days (20.54% vs. 11.96%), with significant increases in length of stay and total hospital charges (p < .001, respectively). CONCLUSIONS: CDI is associated with a large burden on patients and health care systems, significantly increasing hospital utilization, costs and mortality.

The Complement System in the Modern Era of Kidney Transplantation: Mechanisms of Injury and Targeted Therapies.

Kidney transplantation remains the treatment of choice for patients with end-stage kidney disease. Significant progress has been made over the course of many years to improve both patient and graft outcomes after transplant. Modern immunosuppressive therapy has reduced the rate of acute rejection and resulted in excellent short- and long-term graft survival. Over the past decade or so, we have become more cognizant of the role of the complement in many events related to the transplant process. A myriad of events that include the cause of death in deceased donors, organ procurement and preservation events, cold ischemia time, time to kidney anastomosis, ischemia-reperfusion injury, recipient immunologic response during and after transplantation, immunosuppressive drug toxicity, and recurrence of original disease all have been shown to affect graft survival. The involvement of the complement system and its activation around the time of kidney transplantation increasingly is recognized as a key player affecting long-term graft survival. In this review, we highlight the important role of the complement system at every stage of the kidney transplantation process. We review potential triggers of complement activation in kidney transplant patients and discuss novel therapeutic agents that can inhibit the complement system.

Progress in hepatitis C virus management in chronic kidney disease.

PURPOSE OF REVIEW: The current review highlights advances in the use of direct-acting antiviral (DAA) agents in the treatment of hepatitis C virus (HCV) in chronic kidney disease (CKD) stages G4-5, end-stage renal disease, and kidney transplantation. The use of DAA to facilitate kidney transplantation of HCV negative recipients with kidneys from HCV-infected donors and in the management of HCV-related cryoglobulinemia are also reviewed. RECENT FINDINGS: DAA treatment results in rates of viral clearance (sustained virological response or SVR) of 90-100% in all studied CKD populations, comparable to SVR rates in the general population. DAA treatment allows safe and effective transplantation of HCV viremic kidneys into uninfected recipients. SUMMARY: The high SVR results achieved with DAA allow successful treatment of previously under-treated CKD populations, and encouraged innovative interventions such as the use of HCV-infected donor kidneys to uninfected kidney transplant recipients.

Primary Malignant Melanoma of the Urinary Bladder.

There are only 30 reported cases of primary malignant melanoma of the bladder in the literature so far. Of those, 17 cases were reported as deceased within three years of presentation. Our case reported here is that of a 78-year-old female who presented with a new-onset incontinence and intermittent hematuria. She had no evidence of primary melanoma anywhere else in her body. The patient was treated with cystectomy and ileal conduit with plans for adjuvant chemotherapy. Unfortunately, the patient succumbed to her disease with diffuse metastatic involvement within 16 months of presentation.

Advances in BK Virus Complications in Organ Transplantation and Beyond.

Reactivation of BK virus (BKV) remains a dreaded complication in immunosuppressed states. Conventionally, BKV is known as a cause for BKV-associated nephropathy and allograft dysfunction in kidney transplant recipients. However, emerging studies have shown its negative impact on native kidney function and patient survival in other transplants and its potential role in diseases such as cancer. Because BKV-associated nephropathy is driven by immunosuppression, reduction in the latter is a convenient standard of care. However, this strategy is risk prone due to the development of donor-specific antibodies affecting long-term allograft survival. Despite its pathogenic role, there is a distinct lack of effective anti-BKV therapeutics. This limitation combined with increased morbidity and health care cost of BKV-associated diseases add to the complexity of BKV management. While summarizing recent advances in the pathogenesis of BKV-associated nephropathy and its reactivation in other organ transplants, this review illustrates the limitations of current and emerging therapeutic options and provides a compelling argument for an effective targeted anti-BKV drug.

Use of Eculizumab in Transplant-Associated Thrombotic Microangiopathy in a Patient With Polycystic Kidney Disease Immediately Post-Kidney Transplant: A Case Report.

Transplant-associated thrombotic microangiopathy (TMA) in the post-organ transplantation setting occurs from a number of potential inciting factors, such as the use of calcineurin inhibitors, ischemic injury, infections, or antibody-mediated rejection leading to unchecked complement activation and end-organ damage. Delayed recognition of this condition can result in allograft loss. In this case description, we describe the first case of de novo TMA in a patient with polycystic kidney disease that occurred immediately after kidney transplantation. The diagnosis was made promptly on the basis of clinical and laboratory characteristics by a multidisciplinary team and confirmed through kidney biopsy, which showed acute TMA. The patient was successfully managed by replacing tacrolimus with belatacept, which targets cytotoxic T lymphocyte antigen 4, and use of eculizumab, a C5 inhibitor. Eculizumab treatment was discontinued after 3 months of complement inhibition on the patient's request, and relapse of TMA has not been encountered after more than 1 year of follow-up.

The Potential Use of Tumour-Based Prognostic and Predictive Tools in Older Women with Primary Breast Cancer: A Narrative Review.

A move is under way towards personalised cancer treatment, where tumour biology of an individual patient is examined to give unique predictive and prognostic information. This is extremely important in the setting of older women, who have treatment-specific goals which may differ from their younger counterparts, and may include conservation of quality of life rather than curative intent of treatment. One method employed to assist with this is the use of tumour-based prognostic and predictive tools. This article explores six of the most common tumour-based tools currently available on the market: MammaPrint, Oncotype DX, Mammostrat, Prosigna, EndoPredict, IHC4. The article discusses the creation and validation of these tools, their use and validation in older women, and future directions in the field. With the exception of Oncotype Dx, which has also been licensed for prediction of response from adjuvant chemotherapy, these tools have been licensed for use as prognostic tools only, mainly in the setting of adjuvant therapy following surgery. The evidence base for use in older women is strongest for Mammostrat and PAM50, although overall the evidence is much weaker than that in younger women. Where older women have been included in validation studies, this is often in small numbers, or the exact proportion of older women is unknown. In practice, all six of the tools are recommended to be utilised on surgical excision specimens, as well as in core needle biopsy (CNB) specimens in all of the tools except Mammostrat. This is extremely important in the setting of older women, of whom a large proportion do not undergo surgery. The suggested nature of the sample is formalin-fixed paraffin-embedded in all the tools except MammaPrint, which can also be performed on fresh-frozen samples. Future development of prognostic tools in older women with breast cancer should focus on treatment dilemmas specific to this population. This includes the decision of primary treatment between surgery or endocrine therapy and decisions regarding adjuvant therapy, in particular, chemotherapy.

Viral hepatitis in patients on hemodialysis.

Hepatitis B and hepatitis C (HCV) prevalence are higher in people on hemodialysis (HD) than the general population. Through implementation of prevention interventions including vaccines, serologic screening, and post-exposure management, transmissions linked to HD have decreased dramatically. In this manuscript, we review epidemiology of viral hepatitis, summarize current screening and vaccine recommendations, and appraise the available data about efforts to decrease incidence within HD facilities, including isolation of people with viral hepatitis within HD units. Also included is a discussion of the highly effective all-oral HCV treatment options and treatment for HCV in people awaiting kidney transplant.

Summary of the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation.

The 2020 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline on the Evaluation and Management of Candidates for Kidney Transplantation is intended to assist health care professionals worldwide who evaluate and manage potential candidates for deceased or living donor kidney transplantation. This guideline addresses general candidacy issues such as access to transplantation, patient demographic and health status factors, immunological and psychosocial assessment. The roles of various risk factors and comorbid conditions governing an individual's suitability for transplantation such as adherence, tobacco use, diabetes, obesity, perioperative issues, causes of kidney failure, infections, malignancy, pulmonary disease, cardiac and peripheral arterial disease, neurologic disease, gastrointestinal and liver disease, hematologic disease, and bone and mineral disorder are also addressed. This guideline provides recommendations for evaluation of individual aspects of a candidate's profile such that each risk factor and comorbidity are considered separately. The goal is to assist the clinical team to assimilate all data relevant to an individual, consider this within their local health context, and make an overall judgment on candidacy for transplantation. The guideline development process followed the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Guideline recommendations are primarily based on systematic reviews of relevant studies and our assessment of the quality of that evidence. The strengths of recommendations are provided in the full report. Limitations of the evidence are discussed with differences from previous guidelines noted and suggestions for future research are also provided.