纤维性肾小球肾炎(FGN)是一种罕见的免疫介导的肾小球疾病,传统上以淀粉样蛋白样蛋白的存在为特征,随机对齐,毛细血管壁中的纤维沉积,测量直径约20nm,由多克隆IgG组成。FGN通常是原发疾病,没有病理学临床或实验室发现。不止这些,关于光学显微镜评估,它可以接受各种组织学模式,使其诊断无法区分。然而,通过免疫组织化学鉴定一种新的生物标志物,DNA-J热休克蛋白家族成员B9(DNAJB9),即使在没有电子显微镜的情况下,也为FGN诊断创造了一个新时代。通常,大多数患者表现出不同程度的肾功能不全,高血压,镜下血尿,蛋白尿,偶尔会出现弗兰克肾病综合征。预后通常是严重的,进展为终末期肾病(ESKD)是规则,鉴于到目前为止还没有具体的治疗方法,尽管在小型研究中,基于利妥昔单抗的治疗似乎可以减轻严重程度并改善疾病进展。在这里,我们报告了一个63岁的高加索人,他的高血压不受控制,头痛,呼吸急促,下肢水肿。诊断评估显示肾功能轻度恶化,肾病范围蛋白尿,血清和尿液免疫固定中微弱的IgGκ单克隆带。经过对继发性肾病综合征病因的细致调查,患者接受了肾活检.活检样本在光学显微镜下显示两个肾小球系膜扩张和肾小球基底膜(GBM)增厚,一种伪装成膜性肾病III-IV期的模式,而在免疫荧光中,IgG和C3在GBM和系膜上为1-2+。在电子显微镜上发现带有原纤维的加厚GBM,而DNAJB9在免疫组织化学中呈阳性,确认FGN。一旦诊断出FGN,在患者接受标准抗高血压治疗时,开始了类固醇与利妥昔单抗的联合治疗,同时与钠-葡萄糖协同转运蛋白2(SGLT2)抑制剂。12个月的随访显示,蛋白尿减少了约85%,同时肾功能稳定和血压正常化。因此,在这篇文章中,我们的目的是强调DNAJB9相关的FGN可能在光学显微镜下模拟膜性肾小球病III-IV期,特别是当检查GBM原纤维广泛累及的少量肾脏样本时。此外,我们强调了以下事实:超显微镜检查在肾小球沉积疾病的鉴别诊断中至关重要,而DNAJB9在免疫组织化学中的鉴定是FGN诊断中一个革命性且可靠的生物标志物.
Fibrillary glomerulonephritis (FGN) is a rare immune-mediated glomerular disease traditionally characterized by the presence of amyloid-like, randomly aligned, fibrillary deposits in the capillary wall, measuring approximately 20 nm in diameter and composed of polyclonal IgG. FGN is usually a primary disease with no pathognomonic clinical or laboratory findings. More than that, on light microscopic evaluation, it can receive various histological patterns, rendering its diagnosis indistinguishable. However, the identification by immunohistochemistry of a novel biomarker, DNA-J heat-shock protein family member B9 (DNAJB9), has created a new era in FGN diagnosis even in the absence of electron microscopy. Typically, most patients manifest various degrees of renal insufficiency, hypertension, microscopic hematuria, proteinuria, and occasionally frank nephrotic syndrome. The prognosis is usually severe and progression to end-stage kidney disease (ESKD) is the rule, given that no specific treatment is available until now, despite the fact that in small studies rituximab-based therapy seems to alleviate the severity and improve the disease progression. Herein, we report the case of a 63-year-old Caucasian man presenting with uncontrolled hypertension, headache, shortness of breath, and lower limb edema. Diagnostic evaluation revealed mild deterioration of kidney function, nephrotic range proteinuria, and faint IgGκ monoclonal bands in serum and urine immunofixation. After negative meticulous investigation for secondary nephrotic syndrome causes, the patient underwent a kidney biopsy. Biopsy sample showed two glomeruli with mesangial expansion and thickened glomerular basement membrane (GBM) on light microscopy, a pattern masquerading as membranous nephropathy stage III-IV, while IgG and C3 were 1-2+ on GBM and mesangium in immunofluorescence. Thickened GBM with fibrils on electron microscopy were found, while DNAJB9 in immunohistochemistry was positive, confirming FGN. Once diagnosis of FGN was made, a combination of steroids with rituximab was initiated while the patient was receiving the standard anti-hypertensive therapy, simultaneously with a sodium-glucose cotransporter-2 (SGLT2) inhibitor. The 12-month follow-up showed approximately 85% decrease in proteinuria alongside stabilization of kidney function and blood pressure normalization. Hence, in this article, we aim to highlight that DNAJB9-associated FGN may mimic membranous glomerulopathy stage III-IV on light microscopy, especially when a small kidney sample with extensive involvement by fibrils of GBM is examined. Moreover, we underscore the fact that ultramicroscopic examination is of crucial importance in the differential diagnosis of glomerular deposition diseases and that DNAJB9 identification on immunohistochemistry consists of a revolutionary and robust biomarker in FGN diagnosis.