| 1. |
- Anders, Hans Joachim, et al.
(författare)
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Recommendations for the management of patients with immune-mediated kidney disease during the severe acute respiratory syndrome coronavirus 2 pandemic
- 2020
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 35:6, s. 920-925
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Tidskriftsartikel (refereegranskat)abstract
- The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association-European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.
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| 2. |
- Anders, Hans Joachim, et al.
(författare)
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The management of lupus nephritis as proposed by EULAR/ERA 2019 versus KDIGO 2021
- 2023
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Ingår i: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. - : Oxford University Press (OUP). - 1460-2385 .- 0931-0509. ; 38:3, s. 551-561
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Caravaca-Fontán, Fernando, et al.
(författare)
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The management of membranous nephropathy—an update
- 2022
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 37:6, s. 1033-1042
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Da Costa, Mariana Gaya, et al.
(författare)
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Age and sex-associated changes of complement activity and complement levels in a healthy caucasian population
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:NOV
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The complement system is essential for an adequate immune response. Much attention has been given to the role of complement in disease. However, to better understand complement in pathology, it is crucial to first analyze this system under different physiological conditions. The aim of the present study was therefore to investigate the inter-individual variation in complement activity and the influences of age and sex. Methods: Complement levels and functional activity were determined in 120 healthy volunteers, 60 women, 60 men, age range 20-69 year. Serum functional activity of the classical pathway (CP), lectin pathway activated by mannan (MBL-LP) and alternative pathway (AP) was measured in sera, using deposition of C5b-9 as readout. In addition, levels of C1q, MBL, MASP-1, MASP-2, ficolin-2, ficolin-3, C2, C4, C3, C5, C6, C7, C8, C9, factor B, factor D, properdin, C1-inhibitor and C4b-binding protein, were determined. Age- and sex-related differences were evaluated. Results: Significantly lower AP activity was found in females compared to males. Further analysis of the AP revealed lower C3 and properdin levels in females, while factor D concentrations were higher. MBL-LP activity was not influenced by sex, but MBL and ficolin-3 levels were significantly lower in females compared to males. There were no significant differences in CP activity or CP components between females and males, nevertheless females had significantly lower levels of the terminal components. The CP and AP activity was significantly higher in the elderly, in contrast to MBL-LP activity. Moreover, C1-inhibitor, C5, C8, and C9 increased with age in contrast to a decrease of factor D and C3 levels. In-depth analysis of the functional activity assays revealed that MBL-LP activity was predominantly dependent on MBL and MASP-2 concentration, whereas CP activity relied on C2, C1-inhibitor and C5 levels. AP activity was strongly and directly associated with levels of C3, factor B and C5. Conclusion: This study demonstrated significant sex and age-related differences in complement levels and functionality in the healthy population. Therefore, age and sex analysis should be taken into consideration when discussing complement-related pathologies and subsequent complement-targeted therapies.
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| 5. |
- Hilhorst, Marc, et al.
(författare)
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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)
- 2023
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Ingår i: Nephrology, Dialysis and Transplantation. - : OXFORD UNIV PRESS. - 0931-0509 .- 1460-2385. ; 38:8, s. 1807-1816
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Kraaij, Tineke, et al.
(författare)
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Measuring plasma C4D to monitor immune complexes in lupus nephritis
- 2019
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Ingår i: Lupus Science and Medicine. - : BMJ. - 2053-8790. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objective Because currently available assays that measure circulating immune complexes (ICx) are suboptimal, a novel assay was recently developed measuring C4d, a stable product of activation of the classical complement pathway. The present study aimed to establish the value of measuring plasma C4d levels in a longitudinal cohort of patients with severe refractory SLE who were treated with a combination therapy of rituximab with belimumab (RTX+BLM). Methods Fifteen patients with SLE who were treated with RTX+BLM in a phase 2A, open label study were included to sequentially measure plasma C4d levels and correlated to well-established markers of ICx-formation, that is, autoantibodies against double-stranded (ds) DNA, autoantibodies against C1q and proteinuria. The performance of plasma C4d measurements, C4 measurements and the ratio of C4d over C4 (C4d:C4) was evaluated. Results After establishing that on RTX+BLM treatment kinetics of C4d levels was distinct from traditional C3 and C4 levels, we found strong correlation of C4d:C4 with anti-dsDNA (R=0.76, p<0.001) and anti-C1q (R=0.65, p<0.001) autoantibody levels, which outperformed both stand-alone C4 and C4d levels. Additionally, changes in C4d:C4 over time correlated strongly with changes in proteinuria (R=0.59, p<0.001) as well as anti-dsDNA (R=0.46, p=0.003) and anti-C1q (R=0.47, p=0.002). Conclusion In patients with severe SLE, plasma C4d levels in relation to C4 levels is useful for longitudinal monitoring after RTX+BLM treatment to reflect amelioration of classical complement activation by ICx as well as proteinuria.
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| 7. |
- Kronbichler, Andreas, et al.
(författare)
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Recommendations for the use of COVID-19 vaccines in patients with immune-mediated kidney diseases
- 2021
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Ingår i: Nephrology, Dialysis and Transplantation. - : OXFORD UNIV PRESS. - 0931-0509 .- 1460-2385. ; 36:7, s. 1160-1168
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 8. |
- Mirioglu, Safak, et al.
(författare)
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Management of adult patients with podocytopathies: an update from the ERA Immunonephrology Working Group
- 2024
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Ingår i: Nephrology, Dialysis and Transplantation. - : OXFORD UNIV PRESS. - 0931-0509 .- 1460-2385. ; 39:4, s. 569-580
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Tidskriftsartikel (refereegranskat)abstract
- 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. 10.1093/ndt/gfae025 Video Watch the video of this contribution at https://academic.oup.com/ndt/pages/author_videos gfae025Media1 6346336829112
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| 9. |
- Moura, Marta Casal, et al.
(författare)
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Management of antineutrophil cytoplasmic antibody–associated vasculitis with glomerulonephritis as proposed by the ACR 2021, EULAR 2022 and KDIGO 2021 guidelines/recommendations
- 2023
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Ingår i: Nephrology Dialysis Transplantation. - : OXFORD UNIV PRESS. - 0931-0509 .- 1460-2385. ; 38:11, s. 2637-2651
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 10. |
- Stevens, Kate I., et al.
(författare)
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Perspective on COVID-19 vaccination in patients with immune-mediated kidney diseases : consensus statements from the ERA-IWG and EUVAS
- 2022
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Ingår i: Nephrology Dialysis Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 37:8, s. 1400-1410
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Forskningsöversikt (refereegranskat)abstract
- 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 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.
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