Mayer IgA Nephropathy Laboratories, Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.
Front Immunol. 2020 Oct 6;11:572754. doi: 10.3389/fimmu.2020.572754. eCollection 2020.
IgA nephropathy (IgAN) is the commonest biopsy-reported primary glomerulonephritis worldwide. It has an incidence which peaks among young adults, and 30 to 40% of patients' progress to end stage kidney disease within twenty years of diagnosis. Ten-year kidney survival rates have been reported to be as low as 35% in some parts of the world. The successful management of IgAN is limited by an incomplete understanding of the pathophysiology of IgAN and a poor understanding of how pathophysiology may vary both from patient to patient and between patient groups, particularly across races. This is compounded by a lack of rigorously designed and delivered clinical trials in IgAN. This is slowly changing, with a number of Phase 2 and 3 clinical trials of novel therapies targeting a number of different putative pathogenic pathways in IgAN due to report in the next 5 years. From our current, albeit limited, understanding of the pathophysiology of IgAN it is unlikely a single therapy will be effective in all patients with IgAN. The successful management of IgAN in the future is, therefore, likely to be reliant on targeted therapies, carefully selected based on an individualized understanding of a patient's risk of progression and underlying pathophysiology. The potential role of biomarkers to facilitate personalization of prognostication and treatment of IgAN is immense. Here we review the progress made over the past decade in identifying and validating new biomarkers, with a particular focus on those that reflect immunological responses in IgAN.
IgA 肾病(IgAN)是全球最常见的经活检证实的原发性肾小球肾炎。其发病率在年轻人中达到高峰,30%至 40%的患者在诊断后 20 年内进展为终末期肾病。据报道,在世界某些地区,10 年肾脏生存率低至 35%。由于对 IgAN 的病理生理学了解不完整,以及对病理生理学如何在患者之间以及患者群体之间(尤其是在不同种族之间)存在差异的理解不足,成功管理 IgAN 受到限制。这是由于缺乏经过严格设计和实施的 IgAN 临床试验所导致的。这种情况正在慢慢改变,由于有一些针对 IgAN 中许多不同假定致病途径的新型治疗方法的 2 期和 3 期临床试验即将在未来 5 年内报告,这种情况正在慢慢改变。从我们目前对 IgAN 病理生理学的有限了解来看,不太可能有一种单一的疗法对所有 IgAN 患者都有效。因此,未来成功管理 IgAN 可能依赖于基于对患者进展风险和潜在病理生理学的个体化理解而精心选择的靶向治疗。生物标志物在促进 IgAN 的预后和治疗个体化方面具有巨大的潜力。在这里,我们回顾了过去十年在鉴定和验证新的生物标志物方面所取得的进展,特别关注那些反映 IgAN 中免疫反应的生物标志物。