Mayer IgA Nephropathy Laboratories, Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; John Walls Renal Unit, University Hospitals of Leicester NHS Trust, Leicester, UK.
Northwell Health, New Hyde Park, NY; Glomerular Center at Northwell Health, Division of Kidney Diseases and Hypertension, Northwell Health, Great Neck, NY; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY.
Adv Kidney Dis Health. 2024 May;31(3):180-193. doi: 10.1053/j.akdh.2024.04.002.
Primary IgA nephropathy (IgAN) is a common glomerular disorder defined by predominant mesangial IgA deposition. Once thought to follow a progressive course in 10-20% of those diagnosed, emerging evidence now suggests most will progress to kidney failure over their lifetimes. Although the lack of safe and effective treatments to impede disease progression continues to present a challenge, the landscape of IgAN has dramatically evolved over the last 2 years. Driven by fundamental changes to accepted end points for IgAN clinical trials as well as fascinating new insights into the pathophysiology of IgAN, a swathe of novel and repurposed therapies are currently being evaluated. Already, two novel drugs, targeted-release formulation budesonide and sparsentan, have received conditional approvals for the treatment of IgAN, with sodium glucose co-transporter 2 inhibitors establishing themselves as further options. Soon to join this ensemble are likely to be treatments that modulate the complement system and B-cell activity; several are currently undergoing clinical trials in IgAN with promising interim results. In this review, we provide an overview of evolving epidemiological insights, disease mechanisms, emerging therapies, and contemporary challenges surrounding the management of IgAN.
原发性 IgA 肾病（IgAN）是一种常见的肾小球疾病，其特征是主要在系膜区沉积 IgA。过去认为，在诊断出的患者中，有 10-20%的患者会出现进行性疾病，但目前的新证据表明，大多数患者在其一生中都会进展为肾衰竭。尽管缺乏安全有效的治疗方法来阻止疾病进展仍然是一个挑战，但 IgAN 的治疗方法在过去 2 年中发生了巨大的变化。由于 IgAN 临床试验的终点接受了根本性的改变，以及对 IgAN 病理生理学的迷人新见解，目前正在评估一系列新的和重新利用的治疗方法。已经有两种新型药物，即靶向释放布地奈德制剂和 sparsentan，已被批准用于 IgAN 的治疗，而钠-葡萄糖共转运蛋白 2 抑制剂也成为了进一步的选择。很快，可能会有更多的治疗方法加入到这个治疗方案中，这些方法可以调节补体系统和 B 细胞的活性；目前有几种治疗方法正在 IgAN 中进行临床试验，中期结果很有前景。在这篇综述中，我们概述了 IgAN 管理方面不断发展的流行病学见解、疾病机制、新兴治疗方法和当代挑战。
