The Improved Kidney Risk Score in ANCA-Associated Vasculitis for Clinical Practice and Trials.

SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 µ mol/L=0, K1: 250-450 µ mol/L=4, K2: >450 µ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.

Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group.

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.

The management of lupus nephritis as proposed by EULAR/ERA 2019 versus KDIGO 2021.

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.

Prophylactic and early outpatient treatment of COVID-19 in patients with kidney disease: considerations from the Immunonephrology Working Group of the European Renal Association (ERA-IWG).

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.

Management of antineutrophil cytoplasmic antibody-associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations.

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.

The management of membranous nephropathy-an update.

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.

Perspective on COVID-19 vaccination in patients with immune-mediated kidney diseases: consensus statements from the ERA-IWG and EUVAS.

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.

Deprivation and chronic kidney disease-a review of the evidence.

The relationship between socioeconomic deprivation and health is inequitable. Chronic kidney disease (CKD) is an archetypal disease of inequality, being more common amongst those living in deprivation. The prevalence of CKD is rising driven by an increase in lifestyle-related conditions. This narrative review describes deprivation and its association with adverse outcomes in adults with non-dialysis-dependent CKD including disease progression, end-stage kidney disease, cardiovascular disease and all-cause mortality. We explore the social determinants of health and individual lifestyle factors to address whether patients with CKD who are socioeconomically deprived have poorer outcomes than those of higher socioeconomic status. We describe whether observed differences in outcomes are associated with income, employment, educational attainment, health literacy, access to healthcare, housing, air pollution, cigarette smoking, alcohol use or aerobic exercise. The impact of socioeconomic deprivation in adults with non-dialysis-dependent CKD is complex, multi-faceted and frequently under-explored within the literature. There is evidence that patients with CKD who are socioeconomically deprived have faster disease progression, higher risk of cardiovascular disease and premature mortality. This appears to be the result of both socioeconomic and individual lifestyle factors. However, there is a paucity of studies and methodological limitations. Extrapolation of findings to different societies and healthcare systems is challenging, however, the disproportionate effect of deprivation in patients with CKD necessitates a call to action. Further empirical study is warranted to establish the true cost of deprivation in CKD to patients and societies.

Why do we keep ignoring sex in kidney disease?

Throughout the history of nephrology, little attention has been paid to the sex and gender differences in kidney disease. This lack of awareness prevents optimal diagnosis and management of kidney disease. In today's world of precision medicine, it is imperative to appreciate the differential factors regarding gender and kidney disease. This editorial summarizes the up-to-date literature regarding sex and gender differences in kidney disease and considers areas where knowledge is incomplete and where further research is needed. We address sex-specific effects on chronic kidney disease epidemiology; risks of dialysis underdosing and medication overdosing in women; unexplained loss of female sex advantage in life expectancy during dialysis, and impact of sex on diagnosis and management of genetic kidney disease. We also aim to highlight the impact of gender on kidney health and raise awareness of disparities that may be faced by women, and transgender and gender-diverse persons when a male-model approach is used by healthcare systems. By understanding the link between sex and kidney disease, kidney specialists can improve the care and outcomes of their patients. In addition, research on this topic can inform the development of targeted prevention and intervention strategies that address the specific needs and risk factors of different populations.

Immunosuppression Therapy in Kidney Transplantation.

Kidney transplantation is the preferred choice of treatment of end-stage kidney disease (ESKD). Improvement in surgical techniques and immunotherapy has transformed the field of kidney transplantation. Patients undergoing a kidney transplant have a 95% and 90% graft survival rate at one and 5 years. Although advances in immunosuppressive agents have reduced the incidence of acute rejection, the outcome of kidney grafts is still limited by chronic rejection and complications of these medications. The goal of kidney transplantation is to use the combination of immunosuppressive agents that best optimizes allograft and patient survival while limiting drug toxicity and complications. In this review, the immunology of transplantation is described with a focus on current immunosuppressive agents used in kidney transplantation.

Tweet me: conferencing in the era of COVID-19 and 280 characters.

The European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Social Media (SoMe) Team provides Twitter coverage of the annual congress. During the coronavirus disease 2019 (COVID-19) pandemic, #ERAEDTA20 was the first major Nephrology congress to be delivered virtually. The effect of The SoMe Team and the consequences of the COVID-19 pandemic have not been explored previously. Tweets of the ERA-EDTA congresses 2016-20, using official hashtags, were evaluated. Metadata of each tweet were collected prospectively; original tweets, retweets and evidence-based tweets were identified. The gender of tweet author and location of Twitter activity were established. Network maps were created to ascertain the degree of polarization between the 2019 and 2020 Twitter activity, using Gephi 0.9.2. Between 2016 and 2019, the total number of tweets and the number of tweet authors increased, as did the proportion of female authors (20% versus 27%). In 2019, there were fewer multimedia and evidence-based tweets: 8% versus 20% in 2016. Globally, there were fewer Nephrology conferences in 2020 and the number of tweets per day reduced by 53% from 2019. In 2020, The ERA-EDTA congress saw an increase in authors of 9% and only an 8% reduction in tweets. It was easier to disseminate information in 2020, measured by increased correlation coefficient (0.14 versus 0.12 in 2019). A higher proportion of countries was represented (n = 55 versus n = 48 in 2019) and a higher proportion of tweets came from women. In conclusion, the introduction of SoMe Team was associated with increased usage of Twitter and ease of information dissemination. Compared with #nephtwitter activity as a whole in 2020, SoMe Team has mitigated some of the pandemic's deleterious effects in scientific dissemination, relevant to Nephrology.

A roadmap for optimizing chronic kidney disease patient care and patient-oriented research in the Eastern European nephrology community.

Chronic kidney disease (CKD) is a major health problem because of its high prevalence, associated complications and high treatment costs. Several aspects of CKD differ significantly in the Eastern European nephrology community compared with Western Europe because of different geographic, socio-economic, infrastructure, cultural and educational features. The two most frequent aetiologies of CKD, DM and hypertension, and many other predisposing factors, are more frequent in the Eastern region, resulting in more prevalent CKD Stages 3-5. Interventions may minimize the potential drawbacks of the high prevalence of CKD in Eastern Europe, which include several options at various stages of the disease, such as raising public, medical personnel and healthcare authorities awareness; early detection by screening high-risk populations; preventing progression and CKD-related complications by training health professionals and patients; promoting transplantation or home dialysis as the preferred modality; disseminating and implementing guidelines and guided therapy and encouraging/supporting country-specific observational research as well as international collaborative projects. Specific ways to significantly impact CKD-related problems in every region of Europe through education, science and networking are collaboration with non-nephrology European societies who have a common interest in CKD and its associated complications, representation through an advisory role within nephrology via national nephrology societies, contributing to the training of local nephrologists and stimulating patient-oriented research. The latter is mandatory to identify country-specific kidney disease-related priorities. Active involvement of patients in this research via collaboration with the European Kidney Patient Federation or national patient federations is imperative to ensure that projects reflect specific patient needs.