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OBJECTIVES: To evaluate the efficacy and safety of avacopan in the subgroup of patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis receiving background induction therapy with rituximab in the phase 3 ADVOCATE trial. METHODS: Key efficacy outcomes were remission at week 26 and sustained remission at week 52. Additional outcomes included the Glucocorticoid Toxicity Index, estimated glomerular filtration rate, urinary albumin to creatinine ratio, health-related quality of life and safety. RESULTS: Of the 330 patients who received study medication, 214 (64.8%) received rituximab (once weekly for 4 weeks), with a mean age of 59.8 years; 163 (76.2%) had renal vasculitis and 125 (58.4%) were newly diagnosed. Remission at week 26 and sustained remission at week 52 were achieved by 83/107 (77.6%) and 76/107 (71.0%) patients in the avacopan group and 81/107 (75.7%) and 60/107 (56.1%) in the prednisone taper group, respectively. The relapse rate, recovery of renal function, speed of reduction in albuminuria and glucocorticoid toxicity favoured the avacopan group. Serious adverse events occurred in 34.6% and 39.3% of patients in the avacopan and prednisone taper groups, respectively. CONCLUSIONS: These data suggest that in patients with ANCA-associated vasculitis receiving rituximab, efficacy of treatment with avacopan compared with a prednisone taper was similar at week 26 and greater at week 52, with a favourable safety profile. In addition, avacopan was associated with improved renal outcomes and lower glucocorticoid toxicity. These results demonstrate the efficacy and safety of avacopan in patients receiving background induction therapy with rituximab. TRIAL REGISTRATION NUMBER: NCT02994927.
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Compostos de Anilina , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Imunossupressores , Ácidos Nipecóticos , Humanos , Pessoa de Meia-Idade , Rituximab/efeitos adversos , Imunossupressores/uso terapêutico , Prednisona , Glucocorticoides/efeitos adversos , Qualidade de Vida , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Indução de Remissão , Anticorpos Anticitoplasma de NeutrófilosRESUMO
Vaccines offer an effective strategy to prevent infectious diseases with minimal adverse effects. On rare occasions, vaccination can disrupt the immune response leading to induction of autoimmune diseases. We describe a case of new-onset lupus nephritis following COVID-19 vaccination with the first dose of the Pfizer vaccine. Her symptoms and lab values improved with steroids, hydroxychloroquine, and mycophenolate mofetil.
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COVID-19 , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Vacinas , Humanos , Feminino , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Vacinas contra COVID-19 , Quimioterapia Combinada , Lúpus Eritematoso Sistêmico/induzido quimicamente , Ácido Micofenólico/uso terapêuticoRESUMO
PURPOSE OF REVIEW: Pauci-immune crescentic glomerulonephritis is the hallmark finding in ANCA-associated vasculitis (AAV) when the kidneys are affected. The rationale for immunosuppression in AAV is based on the underlying autoimmune nature of the disease. Overall remission rates, kidney outcomes, and the burden of disease have greatly improved since the discovery of various immunosuppressive therapies, but relapses remain common, and a significant proportion of patients continue to progress to end-stage kidney disease. Here, we review the role of immunosuppressive therapies for the treatment of pauci-immune crescentic glomerulonephritis. RECENT FINDINGS: Besides the recognized role of B and T cells in the pathogenies of AAV, the focus on the contribution of inflammatory cytokines, neutrophil extracellular traps (NETs), and the complement system allowed the discovery of new therapies. Specifically, the C5a receptor blocker (avacopan) has been approved as a glucocorticoid-sparing agent. Additionally, based on observational data, more clinicians are now using combination therapies during the induction phase. There is also an evolving understanding of the role of plasma exchange in removing ANCA antibodies. Furthermore, the recent development of risk score systems provides physicians with valuable prognostic information that can influence decisions on immunosuppression, although future validation from larger cohorts is needed. The over-activation of various immune pathways plays a significant role in the pathogenesis of pauci-immune crescentic glomerulonephritis in AAV. Immunosuppression is, therefore, an important strategy to halt disease progression and improve overall outcomes. Relapse prevention while minimizing adverse events of immunosuppression is a major long-term goal in AAV management.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Imunossupressores , Humanos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Glomerulonefrite/imunologia , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/terapia , Imunossupressores/uso terapêutico , Terapia de Imunossupressão/métodos , Insuficiência Renal/etiologiaRESUMO
SIGNIFICANCE STATEMENT: Most patients with anti-glomerular basement membrane (GBM) disease present with rapidly progressive glomerulonephritis, and more than half develop ESKD. Currently, no tools are available to aid in the prognostication or management of this rare disease. In one of the largest assembled cohorts of patients with anti-GBM disease (with 174 patients included in the final analysis), the authors demonstrated that the renal risk score for ANCA-associated vasculitis is transferable to anti-GBM disease and the renal histology is strongly predictive of renal survival and recovery. Stratifying patients according to the percentage of normal glomeruli in the kidney biopsy and the need for RRT at the time of diagnosis improves outcome prediction. Such stratification may assist in the management of anti-GBM disease. BACKGROUND: Prospective randomized trials investigating treatments and outcomes in anti-glomerular basement membrane (anti-GBM) disease are sparse, and validated tools to aid prognostication or management are lacking. METHODS: In a retrospective, multicenter, international cohort study, we investigated clinical and histologic parameters predicting kidney outcome and sought to identify patients who benefit from rescue immunosuppressive therapy. We also explored applying the concept of the renal risk score (RRS), currently used to predict renal outcomes in ANCA-associated vasculitis, to anti-GBM disease. RESULTS: The final analysis included 174 patients (out of a total of 191). Using Cox and Kaplan-Meier methods, we found that the RRS was a strong predictor for ESKD. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-risk, moderate-risk, and high-risk groups, respectively. The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD. The best predictor for renal recovery was the percentage of normal glomeruli, with a cut point of 10% normal glomeruli providing good stratification. A model with the predictors RRT and normal glomeruli ( N ) achieved superior discrimination for significant differences in renal survival. Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N ≥10%), 74.0% (no RRT, N <10%), 42.3% (RRT, N ≥10%), and 14.1% (RRT, N <10%), respectively. CONCLUSIONS: These findings demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Such stratification may assist in the management of anti-GBM disease. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_02_27_JASN0000000000000060.mp3.
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Doença Antimembrana Basal Glomerular , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Humanos , Estudos Retrospectivos , Estudos de Coortes , Estudos Prospectivos , Rim , Terapia de Substituição Renal , Medição de RiscoRESUMO
Immune deposits/complexes are detected in a multitude of tissues in autoimmune disorders, but no organ has attracted as much attention as the kidney. Several kidney diseases are characterised by the presence of specific configurations of such deposits, and many of them are under a 'shared care' between rheumatologists and nephrologists. This review focuses on five different diseases commonly encountered in rheumatological and nephrological practice, namely IgA vasculitis, lupus nephritis, cryoglobulinaemia, anti-glomerular basement membrane disease and anti-neutrophil cytoplasm-antibody glomerulonephritis. They differ in disease aetiopathogenesis, but also the potential speed of kidney function decline, the responsiveness to immunosuppression/immunomodulation and the deposition of immune deposits/complexes. To date, it remains unclear if deposits are causing a specific disease or aim to abrogate inflammatory cascades responsible for tissue damage, such as neutrophil extracellular traps or the complement system. In principle, immunosuppressive therapies have not been developed to tackle immune deposits/complexes, and repeated kidney biopsy studies found persistence of deposits despite reduction of active inflammation, again highlighting the uncertainty about their involvement in tissue damage. In these studies, a progression of active lesions to chronic changes such as glomerulosclerosis was frequently reported. Novel therapeutic approaches aim to mitigate these changes more efficiently and rapidly. Several new agents, such as avacopan, an oral C5aR1 inhibitor, or imlifidase, that dissolves IgG within minutes, are more specifically reducing inflammatory cascades in the kidney and repeat tissue sampling might help to understand their impact on immune cell deposition and finally kidney function recovery and potential impact of immune complexes/deposits.
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Glomerulonefrite , Nefropatias , Nefrite Lúpica , Humanos , Rim/patologia , Nefropatias/diagnóstico , Nefropatias/etiologia , Nefrite Lúpica/patologia , Glomerulonefrite/patologia , Complexo Antígeno-AnticorpoRESUMO
OBJECTIVES: Severe infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors associated with severe infections in participants of the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial. METHODS: Data on 197 patients recruited into the RAVE trial were analysed. Participants received either rituximab (RTX) or cyclophosphamide (CYC), followed by azathioprine (AZA). Clinical and laboratory data of patients with and without severe infections (≥grade 3, according to the Common Terminology Criteria for Adverse Events version 3.0) were compared. Risk factors for severe infections were investigated using Cox-regression models. RESULTS: Eighteen of 22 (82%) severe infections occurred within 6 months after trial entry, most commonly respiratory tract infections (15/22, 68%). At baseline, lower absolute numbers of CD19+ cells were observed in patients with severe infections either receiving RTX or CYC/AZA at baseline, while CD5+B and CD3+T cells did not differ between groups. In Cox-regression analysis, higher baseline serum immunoglobulin M levels were associated with the risk of severe infections, whereby a higher baseline total CD19+B cell number and prophylaxis against Pneumocystis jirovecii with trimethoprim-sulfamethoxazole (TMP/SMX) with decreased risk of severe infections. Use of TMP/SMX was associated with lower risk of severe infections in both groups, receiving either RTX or CYC/AZA. CONCLUSIONS: The use of low-dose TMP/SMX is associated with reduced risk of severe infections in patients with AAV treated with either RTX or CYC/AZA. Reduced B cell subpopulations at start of treatment might be a useful correlate of reduced immunocompetence.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Combinação Trimetoprima e Sulfametoxazol , Humanos , Rituximab/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Anticorpos Monoclonais Murinos , Indução de Remissão , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Azatioprina/uso terapêutico , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVES: We investigated whether soluble immune checkpoints (sICPs) predict treatment resistance, relapse and infections in patients with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). METHODS: Plasma sICP concentrations from available samples obtained during conduct of the RAVE trial were measured by immunoabsorbent assays from patients with either proteinase 3 (PR3) or myeloperoxidase (MPO)-ANCA vasculitis and were correlated with clinical outcomes, a set of biomarkers and available flow cytometry analyses focusing on T cell subsets. Log-rank test was used to evaluate survival benefits, and optimal cut-off values of the marker molecules were calculated using Yeldons J. RESULTS: Analysis of 189 plasma samples at baseline revealed higher concentrations of sTim-3, sCD27, sLag-3, sPD-1 and sPD-L2 in patients with MPO-ANCA vasculitis (n=62) as compared with PR3-ANCA vasculitis (n=127). Among patients receiving rituximab induction therapy (n=95), the combination of lower soluble (s)Lag-3 (<90 pg/mL) and higher sCD27 (>3000 pg/mL) predicted therapy failure. Twenty-four out of 73 patients (32.9%) in the rituximab arm reaching remission at 6 months relapsed during follow-up. In this subgroup, high baseline values of sTim-3 (>1200 pg/mL), sCD27 (>1250 pg/mL) and sBTLA (>1000 pg/mL) were associated with both sustained remission and infectious complications. These findings could not be replicated in 94 patients randomised to receive cyclophosphamide/azathioprine. CONCLUSIONS: Patients with AAV treated with rituximab achieved remission less frequently when concentrations of sLag-3 were low and concentrations of sCD27 were high. Higher concentrations of sTim-3, sCD27 and sBTLA at baseline predicted relapse in patients treated with rituximab. These results require confirmation but may contribute to a personalised treatment approach of AAV.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Mieloblastina , Rituximab/uso terapêutico , Indução de Remissão , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , RecidivaRESUMO
The KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases represents the first update to this set of recommendations since the initial set of KDIGO guideline recommendations was published in 2012. The pace of growth in our molecular understanding of glomerular disease has quickened and a number of newer immunosuppressive and targeted therapies have been introduced since the original set of guideline recommendations, making such an update necessary. Despite these updates, many areas of controversy remain. In addition, further updates since the publication of KDIGO 2021 have occurred which this guideline does not encompass. With this commentary, the KDOQI work group has generated a chapter-by-chapter companion opinion article that provides commentary specific to the implementation of the KDIGO 2021 guideline in the United States.
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Nefropatias , Humanos , Nefropatias/diagnóstico , Nefropatias/terapia , Estados UnidosRESUMO
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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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Síndrome de Churg-Strauss , Glomerulonefrite , Granulomatose com Poliangiite , Falência Renal Crônica , Poliangiite Microscópica , Humanos , Anticorpos Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite/terapia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Poliangiite Microscópica/terapia , Glomerulonefrite/tratamento farmacológico , Falência Renal Crônica/etiologia , Falência Renal Crônica/terapiaRESUMO
BACKGROUND: Treatment of end-stage kidney disease (ESKD) with hemodialysis requires surgical creation of an arteriovenous (AV) vascular access-fistula (AVF) or graft (AVG)-to avoid (or limit) the use of a central venous catheter (CVC). AVFs have long been considered the first-line vascular access option, with AVGs as second best. Recent studies have suggested that, in older adults, AVGs may be a better strategy than AVFs. Lacking evidence from well-powered randomized clinical trials, integration of these results into clinical decision making is challenging. The main objective of the AV Access Study is to compare, between the two types of AV access, clinical outcomes that are important to patients, physicians, and policy makers. METHODS: This is a prospective, multicenter, randomized controlled trial in adults ≥ 60 years old receiving chronic hemodialysis via a CVC. Eligible participants must have co-existing cardiovascular disease, peripheral arterial disease, and/or diabetes mellitus; and vascular anatomy suitable for placement of either type of AV access. Participants are randomized, in a 1:1 ratio, to a strategy of AVG or AVF creation. An estimated 262 participants will be recruited across 7 healthcare systems, with average follow-up of 2 years. Questionnaires will be administered at baseline and semi-annually. The primary outcome is the rate of CVC-free days per 100 patient-days. The primary safety outcome is the cumulative incidence of vascular access (CVC or AV access)-related severe infections-defined as access infections that lead to hospitalization or death. Secondary outcomes include access-related healthcare costs and patients' experiences with vascular access care between the two treatment groups. DISCUSSION: In the absence of studies using robust and unbiased research methodology to address vascular access care for hemodialysis patients, clinical decisions are limited to inferences from observational studies. The goal of the AV Access Study is to generate evidence to optimize vascular access care, based on objective, age-specific criteria, while incorporating goals of care and patient preference for vascular access type in clinical decision-making. TRIAL REGISTRATION: This study is being conducted in accordance with the tenets of the Helsinki Declaration, and has been approved by the central institutional review board (IRB) of Wake Forest University Health Sciences (approval number: 00069593) and local IRB of each participating clinical center; and was registered on Nov 27, 2020, at ClinicalTrials.gov (NCT04646226).
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Fístula Arteriovenosa , Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica , Humanos , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Derivação Arteriovenosa Cirúrgica/métodos , Diálise Renal/métodos , Falência Renal Crônica/terapia , Estudos Retrospectivos , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
The management of immunosuppression utilized in glomerular diseases requires highly nuanced care. Timely recognition and management of these disorders is essential to mitigate the extent of kidney damage. This involves being cognizant of the various classes of immunosuppression, which includes alkylating agents, antimetabolites, calcineurin inhibitors, anti-CD20 therapy, complement inhibitors, corticosteroids, and intravenous immunoglobulin. The mechanisms of action of these drugs, along with associated pharmacokinetics and pharmacodynamics, facets of monitoring, and adverse effects are important aspects with which nephrologists are required to be well versed. In addition, an understanding of therapeutic decisions such as induction and maintenance regimens in the setting of glomerular disease and alteration based on trajectory of disease and subsequent response is imperative. The overarching principle of these strategies of immunosuppression is to achieve a balance of disease mitigation without exposure to inadvertent harm. Special groups such as pregnant women, elderly patients, and patients treated with dialysis are especially susceptible to immunosuppression and thus need highly weighed therapeutic strategies and enhanced surveillance of adverse effects.
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Nefropatias , Ácido Micofenólico , Idoso , Currículo , Feminino , Humanos , Terapia de Imunossupressão , Imunossupressores/efeitos adversos , Nefropatias/induzido quimicamente , Ácido Micofenólico/uso terapêutico , GravidezRESUMO
There continues to be rapid advancement in our understanding of the pathogenesis of immune-mediated kidney disease. This progress has culminated in the development of multiple therapeutic agents that have consistently improved renal and patient outcomes. The focus of this review is to discuss these recent advancements in immune-mediated kidney disease via the lens of direct and indirect immune-mediated mechanisms. In the direct immune-mediated disease, recently described antigens in anti-glomerular basement membrane (GBM) disease and membranous nephropathy are discussed, along with new therapeutic regimens in membranous nephropathy and focal segmental glomerulosclerosis. From an indirect immune-mediated disease standpoint, recent pivotal trials in antineutrophil cytoplasmic antibody vasculitis, lupus nephritis, and IgA nephropathy are examined from a real-world practice perspective. New molecular pathways in various disorders of alternate complement pathway are described, which in turn have led to development of various experimental therapies. In addition, pivotal and ongoing therapeutic trials in the aforementioned diseases are presented.
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Doença Antimembrana Basal Glomerular , Glomerulonefrite por IGA , Glomerulonefrite Membranosa , Nefrite Lúpica , Doença Antimembrana Basal Glomerular/terapia , Glomerulonefrite por IGA/patologia , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/patologia , Humanos , Rim/patologia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologiaRESUMO
Patients with systemic lupus erythematosus (SLE) are at an elevated risk for certain cancers compared to the population at large. Cancers seen at higher rates in the SLE population include hematologic malignancies, such as non-Hodgkin lymphoma, and cancers of the lung and thyroid. SLE patients also have a decreased risk for certain malignancies, such as breast cancer, melanoma, and prostate cancer. We review the literature on risk factors for malignancy in patients with SLE and discuss the exogenous and innate factors that are thought to contribute to the unique pattern of cancer risk observed in this patient population. These risk factors are important for providers of SLE patients to understand in order to maintain high clinical suspicion and detect malignancy as soon as possible. Further research is needed to determine the most effective guidelines on counseling patients on cancer screening and prevention.
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Lúpus Eritematoso Sistêmico , Neoplasias , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Neoplasias/epidemiologia , Neoplasias/etiologia , Fatores de RiscoRESUMO
A dysregulated immune response plays a critical role in systemic lupus erythematosus (SLE) pathogenesis. Environmental factors such as viruses, including coronavirus 2 (COVID-19), have been described to play a role in SLE presentation and exacerbation. These viruses trigger a host's humoral and cellular immunities typically essential in elimination of the viral infection. We present a case of a Hispanic male who developed new-onset lupus nephritis class II after a COVID-19 infection.
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COVID-19 , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , COVID-19/complicações , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Nefrite Lúpica/complicações , MasculinoRESUMO
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.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Poliangiite Microscópica , Humanos , Ácido Micofenólico/uso terapêutico , Anticorpos Anticitoplasma de Neutrófilos , Peroxidase , Imunossupressores/uso terapêutico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Indução de RemissãoRESUMO
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.
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Vacinas contra COVID-19 , Nefropatias , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , Humanos , Nefropatias/tratamento farmacológico , Nefropatias/imunologia , Ácido Micofenólico/uso terapêutico , Rituximab/uso terapêuticoRESUMO
BACKGROUND/OBJECTIVES: Early response to immunosuppressive therapy predicts good renal outcome in lupus nephritis (LN). The purpose of this study was to assess the effect of mycophenolate mofetil (MMF) on the timing of urine protein-to-creatinine ratio reaching 200 mg or less after starting MMF as initial therapy for class III, IV, or V in immunosuppressant-naive patients with LN. METHODS: Patients who had a diagnosis of biopsy-proven LN were included in this cohort study. The initial dose of MMF was 1000 mg twice daily. If no improvement, it was increased to 1500 mg twice daily after 1 month. For statistical analysis, exact binomial distribution 95% confidence intervals were calculated. RESULTS: Nine patients were identified. There were 3 patients with class III, 3 with class IV, 1 with class III to V, 1 with class II to V, and 1 with class V lupus nephritis. The majority were African Americans (70%). At baseline, proteinuria ranged between 0.41 and 4 g, and 88% had normal estimated glomerular filtration rate. Forty-four percent of patients reached 0.28 g of proteinuria within 8 weeks of starting MMF (95% confidence interval, 14%-79%), all of which maintained the same level of response and normal estimated glomerular filtration rate at 12 months. Thirty-three percent of patients achieved the American College of Rheumatology complete response at 8 weeks. CONCLUSIONS: This study demonstrates that only a minority of immunosuppressant-naive LN patients achieved the American College of Rheumatology complete response at 8 weeks after initiation of MMF. A rapid decline in the proteinuria to 0.28 g within the first 8 weeks of the treatment correlated strongly with achieving the same level of response at 12 months.
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Nefrite Lúpica , Ácido Micofenólico , Estudos de Coortes , Creatinina , Ciclofosfamida , Humanos , Imunossupressores , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/tratamento farmacológico , Indução de Remissão , Resultado do TratamentoRESUMO
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.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Nefropatias/epidemiologia , Pneumopatias/epidemiologia , Dermatopatias/epidemiologia , Tromboembolia Venosa/epidemiologia , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Europa (Continente)/epidemiologia , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Rim/imunologia , Nefropatias/imunologia , Pulmão/imunologia , Pneumopatias/imunologia , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Razão de Chances , Análise de Regressão , Estudos Retrospectivos , Pele/imunologia , Dermatopatias/imunologia , Tromboembolia Venosa/imunologiaRESUMO
PURPOSE OF REVIEW: There is ongoing debate concerning the classification of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. That is, whether classification should be based on the serotype (proteinase 3 (PR3)- or myeloperoxidase (MPO)-ANCA) or on the clinical phenotype (granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)). To add clarity, this review focused on integration of the most recent literature. RECENT FINDINGS: Large clinical trials have provided evidence that a serology-based risk assessment for relapses is more predictive than distinction based on the phenotype. Research conducted in the past decade indicated that a serology-based approach more closely resembles the genetic associations, the clinical presentation (i.e., lung involvement), biomarker biology, treatment response, and is also predicting comorbidities (such as cardiovascular death). Our review highlights that a serology-based approach could replace a phenotype-based approach to classify ANCA-associated vasculitides. In future, clinical trials and observational studies will presumably focus on this distinction and, as such, translate into a "personalized medicine."
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Poliangiite Microscópica , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/classificação , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos , Humanos , Mieloblastina , Peroxidase , FenótipoRESUMO
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of disorders characterized by inflammation and destruction of small- and medium-sized blood vessels and the presence of circulating ANCA. Clinical disease phenotypes include granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, and renal-limited vasculitis. Serologic classification of AAV into proteinase 3-ANCA disease and myeloperoxidase-ANCA disease correlates with a number of disease characteristics. AAV has a predilection for the kidney, with >75% of patients having renal involvement characterized by rapidly progressive glomerulonephritis. The cause and pathogenesis of AAV are multifactorial and influenced by genetics, environmental factors, and responses of the innate and adaptive immune system. Randomized controlled trials in the past 2 decades have refined the therapy of AAV and transformed AAV from a fatal disease to a chronic illness with relapsing course and associated morbidity. This article in AJKD's Core Curriculum in Nephrology series provides a detailed review of the epidemiology, pathogenesis, diagnosis, and advances in the management of AAV.