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Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis consists of two main diseases, granulomatosis with polyangiitis and microscopic polyangiitis, and remains among the most devastating and potentially lethal forms of autoimmune inflammatory disease. Granulomatosis with polyangiitis and microscopic polyangiitis are characterised by a necrotising vasculitis that can involve almost any organ, and have generally been studied together. The diseases commonly affect the kidneys, lungs, upper respiratory tract, skin, eyes, and peripheral nerves. Granulomatous inflammation and multinucleated giant cells are key pathological hallmarks of granulomatosis with polyangiitis, but are absent in microscopic polyangiitis. Many immune system events are essential to disease aetiopathogenesis, such as activation of the alternative complement pathway, neutrophil activation via complement receptors, and the influx of inflammatory cells, including monocytes and macrophages. These cells perpetuate inflammation and lead to organ damage. During the 21st century, the management of ANCA-associated vasculitis has moved away from reliance on cytotoxic medications and towards targeted biological medications for both the induction and maintenance of disease remission. Earlier diagnosis, partly the result of more reliable ANCA testing, has led to improved patient outcomes and better survival. Reductions in acute disease-related mortality have now shifted focus to long-term morbidities related to ANCA-associated vasculitis and their treatments, such as chronic kidney disease and cardiovascular disease. Therapeutic approaches in both clinical trials and clinical practice still remain too reliant on glucocorticoids, and continued efforts to reduce toxicity from glucocorticoids remain a priority in the development of new treatment strategies. [ABSTRACT FROM AUTHOR]

The article discusses the use of exome sequencing (ES) as a potential alternative to kidney biopsies in diagnosing undetermined kidney diseases (UKD). While kidney biopsies are invasive and carry risks, recent studies have shown that genetic variants may explain a significant portion of UKD cases. ES involves sequencing the coding regions of all protein-coding genes in the human genome and has been successful in diagnosing certain genetic kidney disorders. However, the study emphasizes that ES does not provide a definitive diagnosis in all cases, and kidney biopsies should still be considered in certain situations. [Extracted from the article]

Chronic nasal carriage of Staphylococcus aureus (SA) has been shown to be significantly higher in GPA patients when compared to healthy subjects, as well as being associated with increased endonasal activity and disease relapse. The aim of this study was to investigate SA involvement in GPA by applying a network-based analysis (NBA) approach to publicly available nasal transcriptomic data. Using these data, our NBA pipeline generated a proteinase 3 (PR3) positive ANCA associated vasculitis (AAV) disease network integrating differentially expressed genes, dysregulated transcription factors (TFs), disease-specific genes derived from GWAS studies, drug–target and protein–protein interactions. The PR3+ AAV disease network captured genes previously reported to be dysregulated in AAV associated. A subnetwork focussing on interactions between SA virulence factors and enriched biological processes revealed potential mechanisms for SA's involvement in PR3+ AAV. Immunosuppressant treatment reduced differential expression and absolute TF activities in this subnetwork for patients with inactive nasal disease but not active nasal disease symptoms at the time of sampling. The disease network generated identified the key molecular signatures and highlighted the associated biological processes in PR3+ AAV and revealed potential mechanisms for SA to affect these processes. [ABSTRACT FROM AUTHOR]

Years of standing still have ended, and the field of nephrology has seen a plethora of clinical trials, changing the therapeutic landscape of chronic kidney disease (CKD) and immune-mediated kidney disease management. POP inhibition might be carried forward to develop therapies that aim to reduce the damage to kidneys caused by ischemia and reperfusion injury, such as after kidney transplantation. Overall, the provided results will further help to increase our understanding of kidney disease in more detail and will eventually lead to individualized treatment approaches for the plethora of kidney diseases. Kidney biopsies remain valuable to a final diagnosis and have achieved enormous value in predicting prognosis in several kidney diseases, such as anti-neutrophil cytoplasmic antibody (ANCA)-glomerulonephritis [[1]]. [Extracted from the article]

The coronavirus disease 2019 (COVID-19) pandemic has disproportionately affected patients with kidney disease, causing significant challenges in disease management, kidney research and trainee education. For patients, increased infection risk and disease severity, often complicated by acute kidney injury, have contributed to high mortality. Clinicians were faced with high clinical demands, resource shortages and novel ethical dilemmas in providing patient care. In this review, we address the impact of COVID-19 on the entire spectrum of kidney care, including acute kidney injury, chronic kidney disease, dialysis and transplantation, trainee education, disparities in health care, changes in health care policies, moral distress and the patient perspective. Based on current evidence, we provide a framework for the management and support of patients with kidney disease, infection mitigation strategies, resource allocation and support systems for the nephrology workforce. [ABSTRACT FROM AUTHOR]

This Viewpoint discusses the potential drawbacks of the use of artificial intelligence (AI) in medicine, for example, the loss of certain skills due to the reliance on AI, and how physicians should consider how to take advantage of the potential benefits of AI without losing control over their profession. [ABSTRACT FROM AUTHOR]

The authors discuss the article "Reclassification of Previously Diagnosed GPA Patients Using the 2022 ACR/EULAR Classification Criteria" by Jung Yoon Pyo et al. Topics include purpose of the Diagnostic and Classification Criteria in Vasculitis (DCVAS) study, reason that classification criteria for diagnosis should be avoided, and the American College of Rheumatology/European Alliance of Associations for Rheumatology ACR/EULAR classification criteria for granulomatosis with polyangiitis (GPA).

Objective To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America. Methods Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs. Results Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15–60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR <15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE. Conclusion Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide   Coronavirus disease 2019 (COVID-19) vaccine platforms are becoming available and are the most promising strategy to curb the spread of severe acute respiratory syndrome coronavirus 2 infections. However, numerous uncertainties exist regarding the pros and cons of vaccination, especially in patients with (immune-mediated) kidney diseases on immunosuppressive drugs. Here, members of the Immunonephrology Working Group of the European Renal Association–European Dialysis and Transplant Association discuss 13 frequently asked questions regarding the safety and efficacy of the most promising vaccine candidates. Post-marketing surveillance should be performed to estimate the rate of vaccine response (humoral and cellular) of different vaccine platforms and disease activity following the administration of COVID-19 vaccines. Some of the candidates induce signalling pathways, which also promote autoimmune kidney diseases, e.g. type I interferons in systemic lupus erythematosus. Efficacy estimates would thus far favour the use of selected COVID-19 vaccines, such as BNT162b2, mRNA-1273 or Gam-COVID-Vac. Humoral immune response after vaccination should be monitored using appropriate assays. Even in the absence of neutralizing antibodies, patients might be protected by a sufficient cellular immune response capable of reducing the severity of COVID-19. A reduced vaccine response after the use of CD20-depleting agents is anticipated and it is particularly important to discuss strategies to improve vaccine response with these patients. Distancing and shielding measures remain important, as not all vaccines fully protect from coronavirus infection. In-depth information about the most pressing vaccine questions is essential to reduce vaccine hesitancy of patients. [ABSTRACT FROM AUTHOR]

The human kidney possesses progenitor cells in the glomerular and tubular compartments of the nephron, capable of self-renewal, proliferation and differentiation. Differentiation of crescent-forming kidney progenitor cells into podocytes attenuates severe glomerulonephritis in mice. The crescent-forming PEC subset in humans was found to be characterized by expression of CD133, a marker of renal progenitor cells, and stratifin, a cell cycle checkpoint protein involved in stem cell proliferation/differentiation. [Extracted from the article]

Both recreational and competitive cycling such as strenuous ultra-cycling have grown in popularity over the last decades. Still, the underlying psychological predictors and their interplay with mental health are unknown. We therefore examined the psychological determinants and health outcomes related to the cycling ambitions of 2,331 international cyclists ranging from commuters via leisure to competitive ultra-cyclists. First, groupwise analysis showed that social and external motives, cycling-induced pain affinity, sensation seeking, benign masochism, low neuroticism, openness, conscientiousness and prior mental health problems most clearly differed between the types of cyclists, with values increasing by level of ambition (commuting vs. leisure vs. competitive). Yet, even within groups, we observed a strong variation of ambition. To capture these nuances, we created a path model with cycling ambition as a latent variable based on five indicators (e.g, frequency of cycling, following a training plan). Path analysis confirmed that social and external motives were important determinants of cycling ambition, partly mediating the effects of masochism and sensation seeking. Furthermore, while partly driven by prior mental health problems, cycling ambition positively predicted current mental health, suggesting that cycling may be a safe way to challenge oneself and potentially serves as a strategy to overcome psychopathological episodes. Longitudinal and qualitative research could follow up on some of the causal relationships proposed in the present model, particularly with regard to ambitious cycling functioning as a potentially unconscious self-therapeutic behavior. [ABSTRACT FROM AUTHOR]

Glucocorticoid exposure remains a major contributor to morbidity and mortality in patients with immune-mediated kidney disease. Recent clinical trials have tested novel potential therapies for these patients and showed that glucocorticoid doses can be reduced without compromising efficacy. Key advances: C5a receptor antagonism with avacopan is effective in combination with cyclophosphamide or rituximab for inducing and maintaining remission in severe anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and reduces glucocorticoid requirements. Reducing glucocorticoid dose with rituximab for the induction of remission in AAV does not compromise short-term efficacy and reduces serious infections. Use of the calcineurin inhibitor voclosporin with mycophenolate mofetil (MMF) and glucocorticoids improves renal response in patients with class III–V lupus nephritis and eGFR >45 ml/min/1.73 m2. Obinutuzumab combined with MMF and glucocorticoids increases renal response in patients with class III–IV lupus nephitis. Inhibition of sodium–glucose co-transporter 2 with dapagliflozin in proteinuric IgA nephropathy improves renal outcomes. [ABSTRACT FROM AUTHOR]

The Coronavirus Disease 2019 (COVID-19) pandemic influenced the management of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. A paucity of data exists on outcome of patients with vasculitis following COVID-19, but mortality is higher than in the general population and comparable to patients undergoing haemodialysis or kidney transplant recipients (reported mortality rates of 20–25%). Delays in diagnosis have been reported, which are associated with sequelae such as dialysis-dependency. Management of ANCA-associated vasculitis has not changed with the aim to suppress disease activity and reduce burden of disease. The use of rituximab, an important and widely used agent, is associated with a more severe hospital course of COVID-19 and absence of antibodies following severe acute respiratory syndrome (SARS)-CoV-2 infections, which prone patients to re-infection. Reports on vaccine antibody response are scarce at the moment, but preliminary findings point towards an impaired immune response, especially when patients receive rituximab as part of their treatment. Seropositivity was reported in less than 20% of patients when rituximab was administered within the prior six months, and the antibody response correlated with CD19+ B-cell repopulation. A delay in maintenance doses, if disease activity allows, has been suggested using a CD19+ B-cell guided strategy. Other immunosuppressive measures, which are used in ANCA-associated vasculitis, also impair humoral and cellular vaccine responses. Regular measurements of vaccine response or a healthcare-policy time-based strategy are indicated to provide additional doses ("booster") of COVID-19 vaccines. This review summarizes a recent educational forum and a recent virtual meeting of the European Vasculitis Society (EUVAS) focusing on COVID-19. • A high proportion of patients with ANCA-associated vasculitis and COVID-19 have a severe disease course with an excess fatality rate. • Antibody response to COVID-19 vaccination is impaired in most patients receiving immunosuppression , and absent in most patients with a recent dose of rituximab. • Antibodies should be regularly monitored, and booster doses may be considered in those with low antibody titres , as neutralisation titres are per se reduced against emerging variants of concern and protection against COVID-19 directly relates to the level of antibody titres. • Patients should continue social distancing measures and vaccination of close contacts is of importance. [ABSTRACT FROM AUTHOR]

The article provides an overview of the 2023 recommendations for the treatment of lupus nephritis (LN) from the European Alliance of Associations for Rheumatology (EULAR). The recommendations emphasize the use of belimumab and voclosporin as add-on therapies for managing active LN. Clinical trials have shown that these medications can improve remission rates and reduce kidney damage. The update also discusses the duration of immunosuppression therapy and the potential value of sodium-glucose cotransporter 2 inhibitors as nephroprotective treatment. The future of LN treatment looks promising with the development of newer therapies and the importance of biomarkers in detecting disease activity and response to therapy. [Extracted from the article]

Objective Data on ANCA-associated vasculitis (AAV) induced by anti-thyroid drugs (ATD) are scarce. We aimed to describe the characteristics and outcome of these patients in comparison to primary AAV. Methods We performed a retrospective multicentre study including patients with ATD-induced AAV. We focused on ATD-induced microscopic polyangiitis (MPA) and compared them with primary MPA by matching each case with four controls by gender and year of diagnosis. Results Forty-five patients with ATD-induced AAV of whom 24 MPA were included. ANCA were positive in 44 patients (98%), including myeloperoxidase (MPO)-ANCA in 21 (47%), proteinase 3 (PR3)-ANCA in six (13%), and double positive MPO- and PR3-ANCA in 15 (33%). Main clinical manifestations were skin involvement (64%), arthralgia (51%) and glomerulonephritis (20%). ATD was discontinued in 98% of cases, allowing vasculitis remission in seven (16%). All the remaining patients achieved remission after glucocorticoids, in combination with rituximab in 11 (30%) or cyclophosphamide in four (11%). ATD were reintroduced in seven cases (16%) without any subsequent relapse. Compared with 96 matched primary MPA, ATD-induced MPA were younger at diagnosis (48 vs 65 years, P  < 0.001), had more frequent cutaneous involvement (54 vs 25%, P  = 0.007), but less frequent kidney (38 vs 73%, P  = 0.02), and a lower risk of relapse (adjusted HR 0.07; 95% CI 0.01, 0.65, P  = 0.019). Conclusion ATD-induced AAV were mainly MPA with MPO-ANCA, but double MPO- and PR3-ANCA positivity was frequent. The most common manifestations were skin and musculoskeletal manifestations. ATD-induced MPA were less severe and showed a lower risk of relapse than primary MPA. [ABSTRACT FROM AUTHOR]

The histopathological lesions, minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are entities without immune complex deposits which can cause podocyte injury, thus are frequently grouped under the umbrella of podocytopathies. Whether MCD and FSGS may represent a spectrum of the same disease remains a matter of conjecture. Both frequently require repeated high-dose glucocorticoid therapy with alternative immunosuppressive treatments reserved for relapsing or resistant cases and response rates are variable. There is an unmet need to identify patients who should receive immunosuppressive therapies as opposed to those who would benefit from supportive strategies. Therapeutic trials focusing on MCD are scarce, and the evidence used for the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) guideline for the management of glomerular diseases largely stems from observational and pediatric trials. In FSGS, the differentiation between primary forms and those with underlying genetic variants or secondary forms further complicates trial design. This article provides a perspective of the Immunonephrology Working Group (IWG) of the European Renal Association (ERA) and discusses the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases focusing on the management of MCD and primary forms of FSGS in the context of recently published evidence, with a special emphasis on the role of rituximab, cyclophosphamide, supportive treatment options and ongoing clinical trials in the field. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real‐world large pharmacovigilance database.We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non‐case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non‐cases). We further analyzed information for the cases of agranulocytosis and AAV.Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake.This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real‐world setting. [ABSTRACT FROM AUTHOR]

In recent decades, insights into the molecular pathways involved in disease have revolutionized the treatment of autoimmune diseases. A plethora of targeted therapies have been identified and are at varying stages of clinical development in renal autoimmunity. Some of these agents, such as rituximab or avacopan, have been approved for the treatment of immune-mediated kidney disease, but kidney disease lags behind more common autoimmune disorders in new drug development. Evidence is accumulating as to the importance of adaptive immunity, including abnormalities in T-cell activation and signaling, and aberrant B-cell function. Furthermore, innate immunity, particularly the complement and myeloid systems, as well as pathologic responses in tissue repair and fibrosis, play a key role in disease. Collectively, these mechanistic studies in innate and adaptive immunity have provided new insights into mechanisms of glomerular injury in immune-mediated kidney diseases. In addition, inflammatory pathways common to several autoimmune conditions exist, suggesting that the repurposing of some existing drugs for the treatment of immune-mediated kidney diseases is a logical strategy. This new understanding challenges the clinical investigator to translate new knowledge into novel therapies leading to better disease outcomes. This review highlights promising immunomodulatory therapies tested for immune-mediated kidney diseases as a primary indication, details current clinical trials and discusses pathways that could be targeted in the future. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic revealed that our understanding of infectious complications and strategies to mitigate severe infections in patients with glomerular diseases is limited. Beyond COVID-19, there are several infections that specifically impact care of patients receiving immunosuppressive measures. This review will provide an overview of six different infectious complications frequently encountered in patients with glomerular diseases, and will focus on recent achievements in terms of vaccine developments and understanding of the use of specific antimicrobial prophylaxis. These include influenza virus, Streptococcus pneumoniae , reactivation of a chronic or past infection with hepatitis B virus in cases receiving B-cell depletion, reactivation of cytomegalovirus, and cases of Pneumocystis jirovecii pneumonia in patients with anti-neutrophil cytoplasmic antibody–associated vasculitis. Varicella zoster virus infections are particularly frequent in patients with systemic lupus erythematosus and an inactivated vaccine is available to use as an alternative to the attenuated vaccine in patients receiving immunosuppressants. As with COVID-19 vaccines, vaccine responses are generally impaired in older patients, and after recent administration of B-cell depleting agents, and high doses of mycophenolate mofetil and other immunosuppressants. Strategies to curb infectious complications are manifold and will be outlined in this review. [ABSTRACT FROM AUTHOR]

Updated guidelines on the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) were released in 2021 by the American College of Rheumatology jointly with the Vasculitis Foundation and, subsequently, in 2022 by the European Alliance of Associations for Rheumatology. In addition, in 2021, the Kidney Disease: Improving Global Outcomes had released updated recommendations on the treatment of AAV with glomerulonephritis (AAV-GN). Kidney involvement is particularly relevant in microscopic polyangiitis and granulomatosis with polyangiitis, but is less frequent in eosinophilic granulomatosis with polyangiitis. The management of AAV-GN has been a focus for drug development and change over the past 10 years. Avoidance of progression to end-stage kidney disease (ESKD) or kidney failure is one of the main unmet needs in the management of AAV, with ESKD having a major impact on morbidity, health costs and mortality risk. Relevant changes in AAV-GN management are related to remission-induction treatment of patients with severe kidney disease, the use of glucocorticoids and avacopan, and remission-maintenance treatment. All the documents provide guidance in accordance with the evidence-based standard of care available at the time of their release. With our work we aim to (i) show the progress made and identify the differences between guidelines and recommendations, (ii) discuss the supporting rationale for those, and (iii) identify gaps in knowledge that could benefit from additional research and should be revised in subsequent updates. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic led to rapid vaccine development and large global vaccination schemes. However, patients with immune-mediated kidney disease, chronic kidney diseases and kidney transplant recipients show high non-response rates to vaccination despite more than three vaccinations and, consequently, reduced viral clearance capacity when infected while receiving certain immunosuppressants, carrying an elevated risk for coronavirus disease 2019 (COVID-19)-related morbidity and mortality. SARS-CoV-2 evolution has been characterized by the emergence of novel variants and spike mutations contributing to waning efficacy of neutralizing antibodies. To this end, the therapeutic field expands from vaccination towards a combined approach of immunization, pre-exposure prophylaxis and early post-exposure treatment using direct-acting antivirals and neutralizing monoclonal antibodies to treat early in the disease course and avoid hospitalization. This expert opinion paper from the Immunonephrology Working Group of the European Renal Association (ERA-IWG) summarizes available prophylactic and/or early treatment options (i.e. neutralizing monoclonal antibodies and direct-acting antivirals) of SARS-CoV-2-infected patients with immune-mediated kidney disease, chronic kidney disease and kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Avoiding end-stage kidney disease in patients with anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV) has a high therapeutic priority. Although renal response is a crucial measure to capture clinically relevant changes, clinal trials have used various definitions and no well-studied key surrogate markers to predict renal outcome in AAV exist. Differences in clinical features and histopathologic and therapeutic approaches will influence the course of kidney function. Its assessment through traditional surrogates (i.e. serum creatinine, glomerular filtration rate, proteinuria, hematuria and disease activity scores) has limitations. Refinement of these markers and the incorporation of novel approaches such as the assessment of histopathological changes using cutting-edge molecular and machine learning mechanisms or new biomarkers could significantly improve prognostication. The timing is favourable since large datasets of trials conducted in AAV are available and provide a valuable resource to establish renal surrogate markers and, likely, aim to investigate optimized and tailored treatment approaches according to a renal response score. In this review we discuss important points missed in the assessment of kidney function in patients with AAV and point towards the importance of defining renal response and clinically important short- and long-term predictors of renal outcome. [ABSTRACT FROM AUTHOR]

The approval of avacopan as a treatment for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) by the US Food and Drug Administration (FDA) in 2021 and the European Medicines Agency (EMA) in 2022 represents an important therapeutic advance. Of the patients receiving avacopan, 13.3% suffered serious infections versus 15.2% in those in the prednisone group, and serious opportunistic infections were less common in patients receiving avacopan (3.6% in the avacopan group, 6.7% in the prednisone group) [[10]]. Insights from the ADVOCATE study: respiratory tract involvement in patients with ANCA-associated vasculitis in a randomized, double-blind, placebo-controlled, phase 3 trial of avacopan. Recovery of renal function among ANCA-associated vasculitis patients with baseline eGFR <=20 in the avacopan ADVOCATE trial. [Extracted from the article]

Little is known about the prevalence of chronic kidney disease (CKD) during the coronavirus disease 2019 (COVID-19) pandemic. We aimed to investigate the long-term trends in CKD prevalence from South Korea including the early pandemic. We used data from 108,152 Korean adults from 2007 to 2020 obtained from a representative longitudinal serial study. We defined CKD as a condition when the participant's estimated glomerular filtration rate was < 60 mL/min/1.73 m2, or one-time spot proteinuria was ≥ 1 +, and then examined the overall trends in the prevalence of CKD. Among the included adults (n = 80,010), the overall national prevalence of CKD was 6.2%. The trend slope gradually increased from 2007 to 2019, however, there was a sudden decrease in 2020 (2007–2010, 5.1% [95% confidence interval (CI) 4.7–5.5]; 2017–2019, 7.1% [95% CI 6.6–7.6]; pandemic period, 6.5% [95% CI 5.7–7.3]; and βdiff, − 0.19; 95% CI − 0.24 to − 0.13). The prevalence of CKD among younger adults and those with poor medical utilization significantly decreased during the early pandemic. This study was the first large-scale study to investigate the longitudinal prevalence of CKD from 2007 to 2020. Further research is needed to fully understand the exact causes for this decline and to identify healthcare policy strategies for preventing and managing CKD. [ABSTRACT FROM AUTHOR]

Background: Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies. Methods: PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor- α (TNF- α), interleukin 1- β (IL-1 β), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof. Results: Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α , IL-6, CRP, but not IL-1 β , are associated with depression. Conclusions: These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported. [ABSTRACT FROM AUTHOR]

In 2019 and 2021, the European League for Rheumatism (EULAR) jointly with the European Renal Association (ERA) and the Kidney Disease: Improving Global Outcomes (KDIGO), respectively, released updated guidelines on the management of lupus nephritis (LN). The Immunology Working Group of the ERA reviewed and compared both updates. Recommendations were either consistent or differences were of negligible clinical relevance for: indication for kidney biopsy, kidney biopsy interpretation, treatment targets, hydroxychloroquine dosing, first-line initial immunosuppressive therapy for active class III, IV (±V) LN, pregnancy in LN, LN in paediatric patients and LN patients with kidney failure. Relevant differences in the recommended management relate to the recognition of lupus podocytopathies, uncertainties in steroid dosing, drug preferences in specific populations and maintenance therapy, treatment of pure class V LN, therapy of recurrent LN, evolving alternative drug options and diagnostic work-up of thrombotic microangiopathy. Altogether, both documents provide an excellent guidance to the growing complexity of LN management. This article endeavours to prevent confusion by identifying differences and clarifying discrepancies. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate updated classification criteria for giant cell arteritis (GCA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate items, 2) prospective collection of candidate items present at the time of diagnosis, 3) expert panel review of cases, 4) data‐driven reduction of candidate items, 5) derivation of a points‐based risk classification score in a development data set, and 6) validation in an independent data set. Results: The development data set consisted of 518 cases of GCA and 536 comparators. The validation data set consisted of 238 cases of GCA and 213 comparators. Age ≥50 years at diagnosis was an absolute requirement for classification. The final criteria items and weights were as follows: positive temporal artery biopsy or temporal artery halo sign on ultrasound (+5); erythrocyte sedimentation rate ≥50 mm/hour or C‐reactive protein ≥10 mg/liter (+3); sudden visual loss (+3); morning stiffness in shoulders or neck, jaw or tongue claudication, new temporal headache, scalp tenderness, temporal artery abnormality on vascular examination, bilateral axillary involvement on imaging, and fluorodeoxyglucose–positron emission tomography activity throughout the aorta (+2 each). A patient could be classified as having GCA with a cumulative score of ≥6 points. When these criteria were tested in the validation data set, the model area under the curve was 0.91 (95% confidence interval [95% CI] 0.88–0.94) with a sensitivity of 87.0% (95% CI 82.0–91.0%) and specificity of 94.8% (95% CI 91.0–97.4%). Conclusion: The 2022 American College of Rheumatology/EULAR GCA classification criteria are now validated for use in clinical research. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate new classification criteria for Takayasu arteritis (TAK). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 6 phases: 1) identification of candidate criteria items, 2) collection of candidate items present at diagnosis, 3) expert panel review of cases, 4) data‐driven reduction of candidate items, 5) derivation of a points‐based classification score in a development data set, and 6) validation in an independent data set. Results: The development data set consisted of 316 cases of TAK and 323 comparators. The validation data set consisted of an additional 146 cases of TAK and 127 comparators. Age ≤60 years at diagnosis and imaging evidence of large‐vessel vasculitis were absolute requirements to classify a patient as having TAK. The final criteria items and weights were as follows: female sex (+1), angina (+2), limb claudication (+2), arterial bruit (+2), reduced upper extremity pulse (+2), reduced pulse or tenderness of a carotid artery (+2), blood pressure difference between arms of ≥20 mm Hg (+1), number of affected arterial territories (+1 to +3), paired artery involvement (+1), and abdominal aorta plus renal or mesenteric involvement (+3). A patient could be classified as having TAK with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the model area under the curve was 0.97 (95% confidence interval [95% CI] 0.94–0.99) with a sensitivity of 93.8% (95% CI 88.6–97.1%) and specificity of 99.2% (95% CI 96.7–100.0%). Conclusion: The 2022 American College of Rheumatology/EULAR classification criteria for TAK are now validated for use in research. [ABSTRACT FROM AUTHOR]

Background Uncertainties exist about the use of mycophenolate mofetil (MMF) in anti-neutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV), particularly for remission maintenance. Methods Systematic review and meta-analysis of phase II and III trials assessing the use of MMF in AAV, granulomatosis with polyangiitis and microscopic polyangiitis (MPA). A comprehensive search of several databases (Medline, EMBASE, Cochrane, Web of Science, Scopus) from inception to 5 May 2020 has been conducted. Trial data were extracted to estimate odds ratios (ORs) and estimates (ES) for MMF efficacy (remission-induction and maintenance). Severe adverse effects (SAEs) were collected. Results From 565 articles captured, 10 met the predefined criteria, 5 phase II and 5 III trials; 4 assessed remission-induction, 3 remission maintenance and 3 both. The pooled OR for remission-induction at 6 months was 1.06 (95% confidence interval 0.74, 1.52), with no significant difference by subgroup meta-analysis of trials stratified by different study-level features (i.e. kidney disease, MPA, myeloperoxidase-ANCA positivity, newly diagnosed disease) (P > 0.05). The overall ES for remission maintenance at the end of follow-up ranged between 51% and 91% (I2 = 74.8%). Subgroup meta-analysis identified kidney involvement as a possible source of heterogeneity, yielding a significantly higher rate of sustained remission in trials enrolling only patients with kidney involvement (92%, 76–100%) versus those enrolling patients with and without kidney involvement (56%, 45–66%). Results were similar in multiple sensitivity analyses. During follow-up, the frequency of SAEs in MMF-based treatment arms was 31.8%. Conclusions In AAV, MMF use was significantly associated with higher sustained remission rates in trials enrolling only patients with kidney involvement. These findings might influence clinical practice. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) comprises granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), that share features of pauci-immune small-vessel vasculitis and the positivity of ANCA targeting proteinase-3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). AAV syndromes are rare, complex diseases and their aetio-pathogenesis is mainly driven by the interaction between environmental and genetic factors. In patients with GPA and MPA, the genetic associations are stronger with ANCA specificity (PR3- versus MPO-ANCA) than with the clinical diagnosis, which, in keeping with the known clinical and prognostic differences between PR3-ANCA-positive and MPO-ANCA-positive patients, supports an ANCA-based re-classification of these disorders. EGPA is also made up of genetically distinct subsets, which can be stratified on ANCA-status (MPO ANCA-positive versus ANCA-negative); these subsets differ in clinical phenotype and possibly in their response to treatment. Interestingly, MPO-ANCA-positive patients with either MPA or EGPA have overlapping genetic determinants, thus strengthening the concept that this EGPA subset is closely related to the other AAV syndromes. The genetics of AAV provides us with essential information to understand its varied phenotype. This Review discusses the main findings of genetic association studies in AAV, their pathogenic implications and their potential effect on classification, management and prognosis. [ABSTRACT FROM AUTHOR]

Sexual health among male cancer survivors is becoming an increasingly important aspect of health care as the number of survivors increases. Here the authors analyse the impact of cancer treatment and cancer types on the prevalence of erectile dysfunction among these men. [ABSTRACT FROM AUTHOR]

Patients with immune-mediated kidney diseases are at increased risk of severe coronavirus disease 2019 (COVID-19). The international rollout of COVID-19 vaccines has provided varying degrees of protection and enabled the understanding of vaccine efficacy and safety. The immune response to COVID-19 vaccines is lower in most patients with immune-mediated kidney diseases; either related to immunosuppression or comorbidities and complications caused by the underlying disease. Humoral vaccine response, measured by the presence of antibodies, is impaired or absent in patients receiving rituximab, mycophenolate mofetil (MMF), higher doses of glucocorticoids and likely other immunosuppressants, such as cyclophosphamide. The timing between the use of these agents and administration of vaccines is associated with the level of immune response: with rituximab, vaccine response can only be expected once B cells start to recover and patients with transient discontinuation of MMF mount a humoral response more frequently. The emergence of new COVID-19 variants and waning of vaccine-induced immunity highlight the value of a booster dose and the need to develop mutant-proof vaccines. COVID-19 vaccines are safe, exhibiting a very low risk of de novo or relapsing immune-mediated kidney disease. Population-based studies will determine whether this is causal or coincidental. Such cases respond to standard management, including the use of immunosuppression. The Immunonephrology Working Group and European Vasculitis Society recommend that patients with immune-mediated kidney diseases follow national guidance on vaccination. Booster doses based on antibody measurements could be considered. [ABSTRACT FROM AUTHOR]

In recent decades, several important advances have taken place in the understanding of the pathogenesis underlying membranous nephropathy (MN) that have sparked renewed interest in its management. Four landmark trials in MN and a fifth clinical trial—which was a pilot study—have been published in recent years. The results from some of these trials have had a significant impact on the recommendations included in the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases, representing a significant step forward compared with the previous guideline in several aspects, including diagnosis, disease monitoring and treatment strategies. However, considering the rapidly evolving advances in the knowledge of MN and the recent publication of the STARMEN and RI-CYCLO trials, several recommendations contained in the guideline warrant updates. This article provides a perspective of the Immunonephrology Working Group of the European Renal Association regarding the management of MN in native kidneys of adult patients. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate revised classification criteria for granulomatosis with polyangiitis (GPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data‐driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points‐based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for GPA consisted of 578 cases of GPA and 652 comparators. The validation set consisted of an additional 146 cases of GPA and 161 comparators. From 91 candidate items, regression analysis identified 26 items for GPA, 10 of which were retained. The final criteria and their weights were as follows: bloody nasal discharge, nasal crusting, or sino‐nasal congestion (+3); cartilaginous involvement (+2); conductive or sensorineural hearing loss (+1); cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti–proteinase 3 ANCA positivity (+5); pulmonary nodules, mass, or cavitation on chest imaging (+2); granuloma or giant cells on biopsy (+2); inflammation or consolidation of the nasal/paranasal sinuses on imaging (+1); pauci‐immune glomerulonephritis (+1); perinuclear ANCA or antimyeloperoxidase ANCA positivity (−1); and eosinophil count ≥1 × 109/liter (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small‐ or medium‐vessel vasculitis could be classified as having GPA if the cumulative score was ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 93% (95% confidence interval [95% CI] 87–96%) and the specificity was 94% (95% CI 89–97%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for GPA demonstrate strong performance characteristics and are validated for use in research. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate classification criteria for microscopic polyangiitis (MPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data‐driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points‐based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for MPA consisted of 149 cases of MPA and 408 comparators. The validation set consisted of an additional 142 cases of MPA and 414 comparators. From 91 candidate items, regression analysis identified 10 items for MPA, 6 of which were retained. The final criteria and their weights were as follows: perinuclear antineutrophil cytoplasmic antibody (ANCA) or anti–myeloperoxidase‐ANCA positivity (+6), pauci‐immune glomerulonephritis (+3), lung fibrosis or interstitial lung disease (+3), sino‐nasal symptoms or signs (−3), cytoplasmic ANCA or anti–proteinase 3 ANCA positivity (−1), and eosinophil count ≥1 × 109/liter (−4). After excluding mimics of vasculitis, a patient with a diagnosis of small‐ or medium‐vessel vasculitis could be classified as having MPA with a cumulative score of ≥5 points. When these criteria were tested in the validation data set, the sensitivity was 91% (95% confidence interval [95% CI] 85–95%) and the specificity was 94% (95% CI 92–96%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for MPA are now validated for use in clinical research. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA). Methods: Patients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in 5 phases: 1) identification of candidate criteria items using consensus methodology, 2) prospective collection of candidate items present at the time of diagnosis, 3) data‐driven reduction of the number of candidate items, 4) expert panel review of cases to define the reference diagnosis, and 5) derivation of a points‐based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators. Results: The development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1 × 109/liter (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti–proteinase 3 ANCA positivity (−3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1), and hematuria (−1). After excluding mimics of vasculitis, a patient with a diagnosis of small‐ or medium‐vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% confidence interval [95% CI] 77–91%) and the specificity was 99% (95% CI 98–100%). Conclusion: The 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for EGPA demonstrate strong performance characteristics and are validated for use in research. [ABSTRACT FROM AUTHOR]

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID‐19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV‐ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC‐CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug‐induced CV‐ADRs from COVID‐19 effects, we restricted analyses to patients with COVID‐19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08–3.29), bradycardia (aOR: 2.09, 95% CI: 1.24–3.53), and hypotension (aOR: 1.67, 95% CI: 1.03–2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC‐CMs in time‐ and dose‐dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin. [ABSTRACT FROM AUTHOR]

Membranoproliferative glomerulonephritis (MPGN) comprises a histologic pattern of glomerular injury with different underlying diseases. Here we report on a 47-year-old female with rapidly progressive glomerulonephritis (RPGN) on top of a previously diagnosed idiopathic MPGN after receiving the first dose of the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) mRNA vaccine. After aggressive immunosuppression her serum creatinine returned to normal values, along with reduction of proteinuria. Recently, numerous publications have reported an association of glomerular diseases with COVID-19 vaccination. Our case presents to the best of our knowledge the first occurrence of possible association of COVID-19 mRNA vaccination with a crescentic form of MPGN. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus is a chronic autoimmune disease characterized by loss of tolerance against nuclear and cytoplasmic self-antigens, induction of immunity and tissue inflammation. Lupus nephritis (LN), the most important predictor of morbidity in SLE, develops in almost 30% of SLE patients at disease onset and in up to 50-60% within the first 10 years. Firstly, in this review, we put the pathogenic mechanisms of the disease into a conceptual frame, giving emphasis to the role of the innate immune system in this loss of self-tolerance and the induction of the adaptive immune response. In this aspect, many mechanisms have been described such as dysregulation and acceleration of cell-death pathways, an aberrant clearance and overload of immunogenic acid-nucleic-containing debris and IC, and the involvement of antigen-presenting cells and other innate immune cells in the induction of this adaptive immune response. This result in a clonal expansion of autoreactive lymphocytes with generation of effector T-cells, memory B-cells and plasma cells that produce autoantibodies that will cause kidney damage. Secondly, we review the immunological pathways of damage in the kidney parenchyma, initiated by autoantibody binding and immune complex deposition, and followed by complement-mediated microvascular injury, activation of kidney stromal cells and the recruitment of leukocytes. Finally, we summarize the rationale for the treatment of LN, from conventional to new targeted therapies, focusing on their systemic immunologic effects and the minimization of podocytary damage. [ABSTRACT FROM AUTHOR]