Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
Division of Nephrology and Hypertension, University of Minnesota, Minneapolis, Minnesota.
Kidney360. 2020 Jul 8;1(9):1002-1013. doi: 10.34067/KID.0002532020. eCollection 2020 Sep 24.
Fibrillary GN (FGN) is a rare glomerular disease that is diagnosed based on the presence of fibrils in glomeruli. The fibrils are typically noncongophilic, randomly oriented, and measure 12-24 nm. Traditionally, electron microscopy (EM) has been an important tool to aid in the diagnosis of FGN by identifying the fibrils and to distinguish it from other entities that could mimic FGN. However, recently DnaJ homolog subfamily B member 9 (DNAJB9) has emerged as both a specific and sensitive biomarker in patients with FGN. It allows prompt diagnosis and alleviates reliance on EM. DNAJB9 is a cochaperone of heat shock protein 70 and is involved in endoplasmic reticulum protein-folding pathways. But its role in the pathogenesis of FGN remains elusive. DNAJB9 may act as a putative antigen or alternatively it may secondarily bind to misfolded IgG in the glomeruli. These hypotheses need future studies to elucidate the role of DNAJB9 in the pathogenesis of FGN. The treatment regimen for FGN has been limited due to paucity of studies. Most patients receive combination immunosuppressive regimens. Rituximab has been studied the most in FGN and it may delay disease progression. Prognosis of FGN remains poor and 50% require dialysis within 2 years of diagnosis. Despite its poor prognosis in native kidneys, the rate of recurrence post-transplantation is low (20%) and patient as well as allograft outcomes are similar to patients without FGN.
纤维状肾小球肾炎 (FGN) 是一种罕见的肾小球疾病，其诊断依据是肾小球中存在纤维。这些纤维通常是非嗜刚果红的，随机定向的，大小为 12-24nm。传统上，电子显微镜 (EM) 一直是通过识别纤维并将其与可能模拟 FGN 的其他实体区分开来，从而协助 FGN 诊断的重要工具。然而，最近 DnaJ 同源物亚家族 B 成员 9 (DNAJB9) 已成为 FGN 患者的特异性和敏感性生物标志物。它可以实现快速诊断，减轻对 EM 的依赖。DNAJB9 是热休克蛋白 70 的共伴侣，参与内质网蛋白折叠途径。但其在 FGN 发病机制中的作用仍不清楚。DNAJB9 可能作为一种假定抗原发挥作用，或者它可能在肾小球中继发性地结合错误折叠的 IgG。这些假说需要进一步研究来阐明 DNAJB9 在 FGN 发病机制中的作用。由于研究较少，FGN 的治疗方案一直受到限制。大多数患者接受联合免疫抑制治疗方案。利妥昔单抗在 FGN 中的研究最多，它可能延缓疾病进展。FGN 的预后仍然较差，50%的患者在诊断后 2 年内需要透析。尽管在原肾中预后较差，但移植后复发率较低（20%），患者和移植物的结局与没有 FGN 的患者相似。
