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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., Competing Interests: The authors have no financial or non-financial potential conflicts of interest to declare related to this project. K.I.S. has received honoraria from Bayer Pharmaceuticals. H.J.A. received honoraria or lecture fees from AstraZeneca, Bayer, Eleva, GlaxoSmithKline, Kezar, Eli Lilly, Novartis, Otsuka, Previpharma and Vifor. A.B. has received honoraria or consulting fees from AstraZeneca, Bayer, ChemoCentryx, Merck/MSD and Vifor. U.S. received honoraria or consulting fees from Ablynx/Sanofi, Alexion Pharma, Allena Pharmaceuticals and Chemocentryx/Vifor. S.P.M. has received honoraria and/or consultancy fees from GlaxoSmithKline, Vifor, Travere and Celltrion. D. Geetha received consulting fees from ChemoCentryx and Aurinia. D.R.W.J. received honoraria or consulting fees from Amgen, Astra-Zeneca, Aurinia, Bristol-Myers Squibb, Boehringer Ingelheim, Chemocentryx, GlaxoSmithKline, National Institute for Health and Care Excellence, Novartis, Otsuka, Roche/Genentech, Takeda, UCB and Vifor. A.K. received honoraria for consulting from Alexion, Otsuka, Catalyst Biosciences, UriSalt, Vifor Pharma and Delta 4 and speaking fees from Vifor Pharma and TerumoBCT. All others report no conflicts of interest related to COVID-19 vaccines., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: The prognosis for kidney survival is poor in patients presenting with circulating anti-glomerular basement membrane (GBM) antibodies and severe kidney injury. It is unknown if treatment with an endopeptidase that cleaves circulating and kidney bound IgG can alter the prognosis., Methods: An investigator-driven phase 2a one-arm study (EudraCT 2016-004082-39) was performed in 17 hospitals in five European countries. A single dose of 0.25 mg/kg of imlifidase was given to 15 adults with circulating anti-GBM antibodies and an eGFR <15 ml/min per 1.73m 2 . All patients received standard treatment with cyclophosphamide and corticosteroids, but plasma exchange only if autoantibodies rebounded. The primary outcomes were safety and dialysis independency at 6 months., Results: At inclusion, ten patients were dialysis dependent and the other five had eGFR levels between 7 and 14 ml/min per 1.73m 2 . The median age was 61 years (range 19-77), six were women, and six were also positive for anti-neutrophil cytoplasmic antibodies. Then 6 hours after imlifidase infusion, all patients had anti-GBM antibodies levels below the reference range of a prespecified assay. At 6 months 67% (ten out of 15) were dialysis independent. This is significantly higher compared with 18% (nine out of 50) in a historical control cohort ( P <0.001, Fisher's exact test). Eight serious adverse events (including one death) were reported, none assessed as probably or possibly related to the study drug., Conclusions: In this pilot study, the use of imlifidase was associated with a better outcome compared with earlier publications, without major safety issues, but the findings need to be confirmed in a randomized controlled trial. Clinical Trial registration number: EUDRACT 2016-004082-39 https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001377-28/results., (Copyright © 2022 by the American Society of Nephrology.)

Objective: To characterize the incidence, type, and risk factors of severe infections (SI) in patients with autoimmune kidney diseases treated with rituximab (RTX)., Methods: We conducted a multicenter retrospective cohort study of adult patients with immune-related kidney diseases treated with at least one course of RTX between 2015 and 2019. As a part of the ABCDE Registry, detailed data on RTX application and SI were collected. SI were defined by Common Terminology Criteria for Adverse Events v5.0 as infectious complications grade 3 and above. Patients were dichotomized between "nephrotic" and "nephritic" indications. The primary outcome was the incidence of SI within 12 months after the first RTX application., Results: A total of 144 patients were included. Twenty-five patients (17.4%) presented with SI, mostly within the first 3 months after RTX administration. Most patients in the nephritic group had ANCA-associated vasculitis, while membranous nephropathy was the leading entity in the nephrotic group. Respiratory infections were the leading SI (n= 10, 40%), followed by urinary tract (n=3, 12%) and gastrointestinal infections (n=2, 8%). On multivariable analysis, body mass index (BMI, 24.6 kg/m 2 versus 26.9 kg/m 2 , HR: 0.88; 95%CI: 0.79-0.99; p=0.039) and baseline creatinine (HR: 1.25; 95%CI: 1.04-1.49; p=0.017) were significantly associated with SI. All patients in the nephritic group (n=19; 100%) who experienced a SI received oral glucocorticoid (GC) treatment at the time of infection. Hypogammaglobulinemia was frequent (58.5%) but not associated with SI., Conclusions: After RTX administration, impaired kidney function and lower BMI are independent risk factors for SI. Patients with nephritic glomerular diseases having concomitant GC treatment might be at higher risk of developing SI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Odler, Windpessl, Krall, Steiner, Riedl, Hebesberger, Ursli, Zitt, Lhotta, Antlanger, Cejka, Gauckler, Wiesholzer, Saemann, Rosenkranz, Eller and Kronbichler.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

A better understanding of the pathophysiology of autoimmune disorders is desired to allow tailored interventions. Despite increased scientific interest a direct pathogenic factor in autoimmune renal disease has been described only in a minority like membranous nephropathy or ANCA-associated vasculitis. Nonetheless the initial step leading to the formation of these antibodies is still obscure. In this review we will focus on the possible role of microbial factors in this context. Staphylococcus aureus may be a direct pathogenetic factor in granulomatosis with polyangiitis (GPA). Chronic bacterial colonization or chronic infections of the upper respiratory tract have been proposed as trigger of IgA vasculitis and IgA nephropathy. Interventions to remove major lymphoid organs, such as tonsillectomy, have shown conflicting results but may be an option in IgA vasculitis. Interestingly no clear clinical benefit despite similar local colonization with bacterial strains has been detected in patients with IgA nephropathy. In systemic lupus erythematosus injection of bacterial lipopolysaccharide induced progressive lupus nephritis in mouse models. The aim of this review is to discuss and summarize the knowledge of microbial antigens in autoimmune renal disease. Novel methods may provide insight into the involvement of microbial antigens in the onset, progression, and prognosis of autoimmune kidney disorders.

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]

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]

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]

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]

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]

Primary membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. Discovery of several antibodies has contributed to an increased understanding of MN. Antibodies against the M-type phospholipase A2 receptor (PLA2R) are present in 50–100% with primary MN and are associated with a lower frequency of spontaneous remission. High levels are linked with a higher probability of treatment resistance, higher proteinuria, and impaired renal function, as well as a more rapid decline of kidney function during follow-up. Immunologic remission precedes reduction of proteinuria by months. Pretransplant evaluation of PLA2R antibodies is warranted to predict recurrence of disease following renal transplantation. Several risk alleles related to the PLA2R1 gene and within the HLA loci have been identified, whereas epitope spreading of PLA2R may predict treatment response. More recently, thrombospondin type 1 domain-containing 7A (THSD7A) antibodies have been discovered in primary MN. Several other rare antigens have been described, including antibodies against neutral endopeptidase as a cause of antenatal MN and circulating cationic bovine serum albumin as an antigen with implications in childhood MN. This review focuses on the progress with a special focus on diagnostic accuracy, predictive value, and treatment implications of the established and proposed antigens. [ABSTRACT FROM AUTHOR]

The administration of iodinated contrast medium (CM) has immediate negative impact on multiple levels of the nephron, including vasoconstriction, an increase in apoptotic pathways and oxidative stress. Therefore, contrast-induced acute kidney injury (CI-AKI) remains an important cause of sudden impairment of renal function. Far from being just a transient phenomenon, CI-AKI has consistently been shown to be associated with adverse outcomes. The phenomenon of chronic kidney disease (CKD) following AKI might explain why this entity portends a poor prognosis in the long run. While it is generally acknowledged that in individuals with normal renal function, the risk of CI-AKI is negligible, pre-existing renal disease is its greatest independent risk factor. Although several recent publications have challenged the dogma of CI-AKI as a stand-alone disease entity, these trials, despite careful propensity matching, are hampered by their retrospective nature. In this article, we concede that there is always a trade-off and that administration of CM may be justified if its diagnostic value is believed to outweigh its associated risks. However, we reason that despite considerable progress in the field, the risk of CI-AKI is still high in the modern era and that CM-based imaging should be employed with great restraint in patients with CKD. [ABSTRACT FROM AUTHOR]

Peripheral blood eosinophilia (PBE), defined as 500 eosinophils or above per microliter (µL) blood, is a condition that is not uncommon but often neglected in the management of patients with chronic kidney disease (CKD), acute kidney injury (AKI), or patients on renal replacement therapy (RRT). The nature of PBE in the context of kidney diseases is predominantly secondary or reactive and has to be distinguished from primary eosinophilic disorders. Nonetheless, the finding of persistent PBE can be a useful clue for the differential diagnosis of underdiagnosed entities and overlapping syndromes, such as eosinophilic granulomatosis with polyangiitis (EGPA), IgG4-related disease (IgG4-RD), acute interstitial nephritis (AIN), or the hypereosinophilic syndrome (HES). For patients on RRT, PBE may be an indicator for bio-incompatibility of the dialysis material, acute allograft rejection, or Strongyloides hyperinfection. In a subset of patients with EGPA, eosinophils might even be the driving force in disease pathogenesis. This improved understanding is already being used to facilitate novel therapeutic options. Mepolizumab has been licensed for the management of EGPA and is applied with the aim to abrogate the underlying immunologic process by blocking interleukin-5. The current article provides an overview of different renal pathologies that are associated with PBE. Further scientific effort is required to understand the exact role and function of eosinophils in these disorders which may pave the way to improved interdisciplinary management of such patients. [ABSTRACT FROM AUTHOR]