Department of Medicine, MedStar Georgetown University Hospital, Washington, DC, United States.
National Kapodistrian University of Athens Medical School, Athens, Greece.
Autoimmun Rev. 2023 Jun;22(6):103327. doi: 10.1016/j.autrev.2023.103327. Epub 2023 Mar 28.
The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased over the past decades, imposing a growing socioeconomic burden on healthcare systems globally. Most of the morbidity and mortality related to IBD is typically attributed to gut inflammation and its complications; yet the disease is characterized by various extraintestinal manifestations that can be severe. Glomerulonephritis (GN) is of particular interest since a significant proportion of patients evolve into end-stage kidney disease, requiring kidney replacement therapy and associated with high morbidity and mortality. Herein, we review the GN landscape in IBD and define the clinical and pathogenic associations reported to date in the literature. Underlying pathogenic mechanisms suggest either the initiation of antigen-specific immune responses in the inflamed gut that cross react with non-intestinal sites, such as the glomerulus, or that extraintestinal manifestations are gut-independent events that occur due to an interaction between common genetic and environmental risk factors. We present data associating GN with IBD either as a bona fide extraintestinal manifestation or reporting it as an extraneous co-existing entity, involving various histological subtypes, such as focal segmental glomerulosclerosis, proliferative GN, minimal change disease, crescentic GN, but most emphatically IgA nephropathy. Supporting the pathogenic interplay between gut inflammation and intrinsic glomerular processes, enteric targeting the intestinal mucosa with budesonide reduced IgA nephropathy-mediated proteinuria. Elucidating the mechanisms at play would provide insight not only into IBD pathogenesis but also into the gut's role in the development of extraintestinal diseases, such as glomerular diseases.
过去几十年中，炎症性肠病（IBD）的发病率和患病率有所增加，给全球医疗保健系统带来了日益增长的社会经济负担。IBD 相关的大多数发病率和死亡率通常归因于肠道炎症及其并发症；然而，该疾病的特征是各种严重的肠道外表现。肾小球肾炎（GN）尤其受到关注，因为相当一部分患者会发展为终末期肾病，需要肾脏替代治疗，并且伴有高发病率和死亡率。本文综述了 IBD 中的 GN 情况，并定义了迄今为止文献中报道的与临床和发病机制相关的关联。潜在的发病机制表明，要么是在炎症肠道中启动了针对抗原的特异性免疫反应，这些反应与非肠道部位（如肾小球）发生交叉反应，要么是肠道外表现是与肠道无关的事件，是由于常见遗传和环境危险因素之间的相互作用而发生的。我们提出了将 GN 与 IBD 相关联的证据，要么作为真正的肠道外表现，要么报告为同时存在的无关实体，涉及各种组织学亚型，如局灶节段性肾小球硬化、增生性 GN、微小病变性肾病、新月体性 GN，但最强调的是 IgA 肾病。肠道炎症和固有肾小球过程之间的致病相互作用得到了支持，用布地奈德靶向肠道黏膜可以减少 IgA 肾病介导的蛋白尿。阐明其中的机制不仅可以深入了解 IBD 的发病机制，还可以深入了解肠道在发展肠道外疾病（如肾小球疾病）中的作用。
