Characteristic electron-microscopic features of cryofibrinogen-associated glomerulonephritis: a case report

Abstract

Background: Cryofibrinogenemia is a rare disorder that mainly affects the skin and occasionally the kidney. However, there are few published reports of cryofibrinogenemia-associated renal pathology. We therefore report a patient with cryofibrinogen-associated glomerulonephritis. Samples from this patient were examined by electron microscopy, laser microdissection, and liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Case presentation: A 78-year-old Japanese man presented with declining renal function, proteinuria, and gross hematuria. Kidney biopsy showed a membranoproliferative pattern with crescent formation and dominant C3c deposition in which subendothelial deposits with uniquely organized electron-microscopic features were observed. Additional ultrastructural analysis of cryoprecipitates extracted from plasma revealed similar structures of the glomerular subendothelial deposits. LC-MS/MS identified an increase in fibrinogen α, β, and γ chains, fibronectin, filamin-A, and C3. The glomerular lesions were diagnosed as cryofibrinogen-associated glomerulonephritis on the basis of these findings.

Conclusions: Although there are few reports of cryofibrinogen-associated glomerulonephritis, we believe that accurate diagnosis can be achieved by performing LC-MS/MS and ultrastructural analysis.

Keywords: Cryofibrinogen; Cryofibrinogen-associated glomerulonephritis; Membranoproliferative glomerulonephritis; Microtubular structure; Organized deposit.

Fig. 1

Light microscopy and immunofluorescence microscopy findings. a–c Membranoproliferative glomerulonephritis with crescent formation. Neutrophils are present in the capillary lumens. (a: hematoxylin and eosin stain, b: periodic acid-Schiff stain, c: periodic acid methenamine silver stain); d–f staining for C3 (d), IgM (e) and weak staining for fibrinogen (f). (a–e: original magnification, 40×)

Fig. 2

Patient’s serum (A) and EDTA plasma (B) were stored for 48 h at 4 °C, after which they were stored for 18 h at 37 °C (A, B). Cryoprotein was precipitated from plasma but not from serum. The cryoprecipitate redissolved at 37 °C

Fig. 3

Electron microscopy. a, b Subendothelial deposits in glomeruli. Unique deposits characterized by randomly arranged large fibrils with large central bores and double layer structures are apparent. (c) Cryoprecipitate. Similar structures to the subendothelial deposits in glomeruli are apparent. (Original magnification, a: 4000×, b: 12,000×, c: 8000×)

Fig. 4

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) using Mascot and Scaffold database identified increased fibrinogen α, β, and γ chains, fibronectin, filamin-A, and C3

Fig. 5

Treatment and progress of kidney function. S-Cr, serum creatinine level