Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.
Keywords: MGUS; MPGN; cryofibrinogen; cryoprotein; fibrinogen kidney disease; kidney biopsy; membranoproliferative glomerulonephritis.