Plasma-negative, Renal-limited Cryofibrinogen-associated Glomerulonephritis: A Unique Case Report

Abstract

Cryofibrinogen-associated glomerulonephritis is characterized by membranoproliferative glomerulonephritis without immunoglobulin deposition and unique ultrastructural features. This case report presents a 63-year-old man with renal-limited cryofibrinogen-associated glomerulonephritis, with negative plasma cryofibrinogen levels. His medical history included metallic aortic valve replacement and long-term anticoagulation therapy. Clinical examination revealed no cutaneous manifestations or thrombotic events. Initial laboratory investigations showed severe kidney dysfunction, but negative results for plasma cryofibrinogen, serum cryoglobulin, and a comprehensive autoimmune, infective, and malignancy panel. Kidney biopsy revealed mesangiocapillary glomerulonephritis with focal vasculitis and significant interstitial fibrosis, and electron microscopy identified double-walled microtubules consistent with cryofibrinogen. Our patient was managed without immunosuppressive therapy due to significant kidney scarring and absence of extra-renal manifestations. To our knowledge, this case describes the first report of cryofibrinogen-associated glomerulonephritis in the absence of detectable cryofibrinogen in serum, with diagnosis relying on ultrastructural findings. Differential diagnoses such as immunotactoid glomerulonephritis were considered but ruled out based on morphological characteristics. This case adds to the limited literature on renal-limited cryofibrinogen and emphasizes the necessity for thorough investigation including electron microscopy assessment of kidney biopsies to ascertain the diagnosis.

Keywords: Biopsy-proven; cryofibrinogen; glomerulonephritis.

Figure 1

A rounded eosinophilic deposit, resembling a “pseudothrombus,” was seen within a glomerular capillary loop on hemotoxylin and eosin (H&E) (A) and periodic acid–Schiff/methanamine silver staining (B). Endocapillary lesions formed by inflammatory cells and swollen endothelial cells plugging capillary loops were readily seen, as was focal mesangial hypercellularity (C, alcian blue/periodic acid–Schiff; D, H&E), with rare double contours (not pictured), indicating a membranoproliferative pattern of injury. A focus of acute vasculitis with intraluminal thrombus was also noted on H&E staining (E). Immunofluorescent labeling for fibrinogen, showing segmental glomerular capillary loop labeling (F). Immunoglobulins were effectively nonspecific weak to negative, while C3 showed weak granular labeling (not pictured).

Figure 2

Electron microscopy of deparaffinized tissue. Top panel: Low magnification view of a glomerular capillary loop occluded by endothelial proliferation and leukocytic infiltration. Abundant electron-dense material is present within the subendothelial margins. Middle panel: Higher magnification view of the subendothelial material. Bottom panel: Very high magnification reveals the tubular nature of the material. In cross-section, the tubules display single and double walls. These microtubules were approximately 100 nm in outer diameter, with a hollow core consistent with cryofibrinogen.