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.

Discontinuing Hemodialysis through Corticosteroid Treatment in a Patient with Cryofibrinogen-associated Glomerulonephritis

“…However, in our case, the characteristic formation of large subendothelial fibrils was a limited finding and was only detected in the second kidney biopsy, in contrast to the global glomerular changes. Notably, some cases exhibit a segmental pattern of fibrinogen staining, similar to our case, despite the overall glomerular changes observed in those cases (2,4,5). The contribution of thrombotic vasculopathy by cryofibrinogen (7) was also unclear in our case of Cry-oFiGN.…”

“…Although we were unable to confirm the presence of cryofibrinogen in our patient's plasma, we diagnosed the patient with CryoFiGN based on the clinical presentation, MPGN-like glomerulonephritis without immunoglobulin depositions but with fibrinogen depositions, absence of electron-dense deposits, presence of subendothelial large fibrils with tubular structures, and evidence of fibrinogen depositions by LC-MS/MS. Immunotactoid glomerulonephritis also shows large microtubular substructures, but their diameters are up to 90 nm, and large tubular structures in CryoFiGN have diameters ranging from 40 to 50, 60, or 121 to 220 nm with multilamellar tubular structures similar to those in our case (2,(4)(5)(6). Awareness of the differential diagnosis of CryoFiGN in patients with MPGN-like glomerulonephritis without immunoglobulin deposition is important.…”

“…Foot-process effacement was observed in Because there were no electron-dense deposits, immune complex-mediated glomerulonephritis and C3 nephropathy were ruled out. Given the clinical presentation and MPGNlike glomerulonephritis with non-immunoglobulin deposition and subendothelial large fibrils with microtubular structures, CryoFiGN was suspected (2,4). Laser microdissection and liquid chromatography-tandem mass spectrometry (LC-MS/ MS) of glomeruli from paraffin sections were performed ( 5), revealing increased levels of IgG1, IgG2, immunoglobulin κ and λ, complement 3 and 4, fibronectin, and fibrinogen α, β, and γ chains (Fig.…”

Cryofibrinogen-associated glomerulonephritis accompanied by advanced gastric cancer

“…In our patient, organized deposits were small tubular-like and had relatively thinner diameter. In the electronic microscope, settled protein in plasma shows the tubular structure, which is similar to those observed in the glomerulus [3,15], although we could not assess it. In plasma, the settlement of fibrinogen might be facilitated when fibronectin connects fibrin and fibrinogen [16].…”

“…Approximately 10% of patients with cryofibrinogenemia had some renal disease [7,11]. However, its detailed pathological assessments remain unreported [3,[12][13][14][15]. Sethi and colleagues reported two cases as cryofibrinogen-associated glomerulonephritis [3].…”