Terzolo Edoardo, Solfietti Laura, Ferro Michela, Barreca Antonella, Milan Massimo, Fenoglio Roberta, Sciascia Savino, Roccatello Dario
University Center of Excellence on Nephrologic, Rheumatologic and Rare Diseases (ERK-Net, ERN-Reconnect and RITA-ERN Member) with Nephrology and Dialysis Unit and Center of Immuno-Rheumatology and Rare Diseases (CMID), Coordinating Center of the Interregional Network for Rare Diseases of Piedmont and Aosta Valley, San Giovanni Bosco Hub Hospital ASL Città di Torino and Department of Clinical and Biological Sciences, 10154 Turin, Italy.
Division of Pathology, Città Della Salute e Della Scienza Hospital, University of Turin, 10154 Turin, Italy.
J Clin Med. 2025 Feb 28;14(5):1656. doi: 10.3390/jcm14051656.
: Cryofibrinogenemia, characterized by plasma cryoprecipitation of fibrinogen and related proteins, is a rare and often under-recognized entity that can present with significant renal involvement. : we describe a 66-year-old woman with progressive renal failure due to membranoproliferative glomerulonephritis driven by cryofibrinogen deposits. Her clinical course was marked by relapsing-remitting disease with limited response to high-dose corticosteroids but significant improvement following plasma exchange. Over seven years, she underwent three kidney biopsies, revealing progressive histopathological changes, including glomerular cryofibrinogen deposits and evolving chronicity. A detailed review of the literature identified 50 cases of cryofibrinogenemia, highlighting its association with monoclonal gammopathies, malignancies, and autoimmune diseases. : our case uniquely underscores the pathogenic interplay between cryofibrinogenemia and a monoclonal IgG-kappa paraprotein, which was found to directly stabilize fibrinogen and drive cryoprecipitation. This novel observation aligns cryofibrinogenemia with monoclonal gammopathy of renal significance, expanding the diagnostic and therapeutic landscape for this entity. : this report also highlights the pivotal role of kidney biopsy with electron microscopy in diagnosing cryofibrinogen-associated renal disease, particularly when conventional biomarkers are insufficient. Moreover, our findings emphasize the therapeutic utility of plasmapheresis and the potential need for therapies aimed at eliminating the pathogenetic monoclonal antibody in managing refractory cases. Enhanced awareness and further research into this rare entity are essential for advancing patient care and outcomes.
冷纤维蛋白原血症的特征是纤维蛋白原和相关蛋白在血浆中发生冷沉淀，是一种罕见且常未被充分认识的疾病，可伴有严重的肾脏受累。我们描述了一名66岁女性，因冷纤维蛋白原沉积导致的膜增生性肾小球肾炎而出现进行性肾衰竭。她的临床病程以复发-缓解型疾病为特征，对高剂量皮质类固醇反应有限，但血浆置换后有显著改善。在七年多的时间里，她接受了三次肾脏活检，显示出进行性的组织病理学变化，包括肾小球冷纤维蛋白原沉积和慢性病变的进展。对文献的详细回顾确定了50例冷纤维蛋白原血症病例，突出了其与单克隆丙种球蛋白病、恶性肿瘤和自身免疫性疾病的关联。我们的病例独特地强调了冷纤维蛋白原血症与单克隆IgG-κ副蛋白之间的致病相互作用，发现该副蛋白可直接稳定纤维蛋白原并驱动冷沉淀。这一新颖的观察结果将冷纤维蛋白原血症与具有肾脏意义的单克隆丙种球蛋白病联系起来，拓宽了该疾病的诊断和治疗视野。本报告还强调了肾活检及电子显微镜检查在诊断冷纤维蛋白原相关肾病中的关键作用，尤其是在传统生物标志物不足时。此外，我们的研究结果强调了血浆置换的治疗效用以及在治疗难治性病例中针对消除致病性单克隆抗体的潜在治疗需求。提高对这一罕见疾病的认识并进一步开展研究对于改善患者护理和治疗结果至关重要。
