Division of Nephrology, Department of Medicine, Stanford University, Stanford, California, USA.
Division of Nephrology, Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.
Am J Nephrol. 2018;47 Suppl 1:43-52. doi: 10.1159/000481636. Epub 2018 May 31.
Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis and has clinical associations with a wide range of inflammatory and infectious diseases. There is a substantial variation in clinical course and outcomes, with many patients not diagnosed until they present with sequelae, which may include gross hematuria, hypertension, renal insufficiency, and/or significant proteinuria. Treatment options are currently limited and directed mainly toward control of these sequelae and have limited ability to reduce the incidence of end-stage renal disease or treat the primary IgA defect.
Growing knowledge about the pathogenesis of IgA nephropathy and research into its genetic basis are helping to elucidate the course of this widely variable disease. IgA accumulation in the kidneys is thought to be the result of a number of different pathways in a "multi-hit" process that includes an initial traumatic trigger (often infection related) and subsequent memory responses that are amplified in those with a genetic predisposition to the disease and lead to an inflammatory response in susceptible individuals. Genome-wide association studies are providing new insights into the genetic variance of this autoimmune disease and are yielding information that may address both its causes and consequences. Key Messages: New treatment approaches are urgently required for the management of patients with IgA nephropathy. Novel interventions based around its inflammatory nature and "multi-hit" pathogenesis are being investigated to potentially limit disease progression.
免疫球蛋白 A（IgA）肾病是原发性肾小球肾炎中最常见的一种形式，与多种炎症和感染性疾病有临床关联。其临床病程和结局存在很大差异，许多患者直到出现血尿、高血压、肾功能不全和/或大量蛋白尿等后遗症时才被诊断出来。目前的治疗选择有限，主要针对控制这些后遗症，并且减少终末期肾病的发生率或治疗原发性 IgA 缺陷的能力有限。
对 IgA 肾病发病机制的不断深入了解和对其遗传基础的研究，有助于阐明这种广泛存在差异的疾病的病程。IgA 在肾脏中的积累被认为是“多打击”过程中许多不同途径的结果，其中包括初始创伤性触发（通常与感染有关）和随后的记忆反应，这些反应在具有疾病遗传易感性的人群中被放大，并导致易感个体发生炎症反应。全基因组关联研究为这种自身免疫性疾病的遗传变异提供了新的见解，并提供了可能解决其病因和后果的信息。
迫切需要新的治疗方法来管理 IgA 肾病患者。正在研究基于其炎症性质和“多打击”发病机制的新干预措施，以潜在地限制疾病进展。
