Karam Sabine, Haidous Mohamad, Royal Virginie, Leung Nelson
Division of Nephrology and Hypertension, University of Minnesota, Minneapolis, Minnesota, USA.
Department of Medicine, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA.
Kidney Int. 2023 Mar;103(3):473-484. doi: 10.1016/j.kint.2022.10.028. Epub 2022 Dec 9.
Amyloid A amyloidosis is thought to be the second most common form of systemic amyloidosis behind amyloidosis secondary to monoclonal Ig. It is the result of deposition of insoluble fibrils in the extracellular space of tissues and organs derived from the precursor protein serum amyloid A, an acute phase reactant synthesized excessively in the setting of chronic inflammation. The kidney is the most frequent organ involved. Most patients present with proteinuria and kidney failure. The diagnosis is made through tissue biopsy with involvement of the glomeruli in most cases, but also often of the vessels and the tubulointerstitial compartment. The treatment usually targets the underlying etiology and consists increasingly of blocking the inflammatory cascade of cytokines with interleukin-1 inhibitors, interleukin-6 inhibitors, and tumor necrosis factor-α inhibitors to reduce serum amyloid A protein formation. This strategy has also shown efficacy in cases where an underlying etiology cannot be readily identified and has significantly improved the prognosis of this entity. In addition, there has been increased interest at developing effective therapies able to clear amyloid deposits from tissues, albeit with mitigated results so far.
淀粉样蛋白A淀粉样变性被认为是继单克隆Ig继发性淀粉样变性之后第二常见的系统性淀粉样变性形式。它是不溶性纤维在组织和器官细胞外空间沉积的结果,这些纤维源自前体蛋白血清淀粉样蛋白A,这是一种在慢性炎症情况下过度合成的急性期反应物。肾脏是最常受累的器官。大多数患者表现为蛋白尿和肾衰竭。诊断通过组织活检进行,在大多数情况下累及肾小球,但血管和肾小管间质部分也常受累。治疗通常针对潜在病因,越来越多地包括使用白细胞介素-1抑制剂、白细胞介素-6抑制剂和肿瘤坏死因子-α抑制剂阻断细胞因子的炎症级联反应,以减少血清淀粉样蛋白A的形成。这种策略在无法轻易确定潜在病因的情况下也显示出疗效,并显著改善了该疾病的预后。此外,人们对开发能够清除组织中淀粉样沉积物的有效疗法的兴趣日益增加,尽管迄今为止结果有限。