{"title":"Kidney Failure in Pauci-immune Crescentic Glomerulonephritis: Rationale for Immunosuppression to Improve Kidney Outcome.","authors":"Faten Aqeel, Duvuru Geetha","doi":"10.1007/s11926-024-01150-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p>","PeriodicalId":10761,"journal":{"name":"Current Rheumatology Reports","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Rheumatology Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11926-024-01150-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
综述的目的:当肾脏受到影响时,帕奇免疫新月体肾小球肾炎是 ANCA 相关性血管炎(AAV)的标志性发现。对 AAV 进行免疫抑制的依据是该病潜在的自身免疫性质。自发现各种免疫抑制疗法以来,总体缓解率、肾脏预后和疾病负担已大大改善,但复发仍很常见,相当一部分患者会继续发展为终末期肾病。在此,我们回顾了免疫抑制疗法在治疗贫免疫性新月体肾小球肾炎中的作用:除了公认的 B 细胞和 T 细胞在新月体肾小球肾炎病因中的作用外,炎性细胞因子、中性粒细胞胞外捕获物(NET)和补体系统的作用也受到了关注,这使得新疗法的发现成为可能。具体而言,C5a 受体阻断剂(avacopan)已被批准作为一种糖皮质激素节约剂。此外,根据观察数据,现在越来越多的临床医生在诱导阶段使用联合疗法。人们对血浆置换在清除 ANCA 抗体中的作用的认识也在不断发展。此外,最近开发的风险评分系统为医生提供了有价值的预后信息,可以影响免疫抑制的决策,但未来还需要更大规模的队列验证。各种免疫途径的过度激活在 AAV 贫免疫性新月体肾小球肾炎的发病机制中起着重要作用。因此,免疫抑制是阻止疾病进展和改善总体预后的重要策略。预防复发,同时尽量减少免疫抑制的不良反应,是 AAV 治疗的一个主要长期目标。
期刊介绍:
This journal aims to review the most important, recently published research in the field of rheumatology. By providing clear, insightful, balanced contributions by international experts, the journal intends to serve all those involved in the care and prevention of rheumatologic conditions.
We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas such as the many forms of arthritis, osteoporosis and metabolic bone disease, and systemic lupus erythematosus. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also occasionally provided.