Membranoproliferative Glomerulonephritis with Striated Ultrastructural Deposits with Significantly Elevated Fibrinogen and Fibronectin on Mass Spectrometry Analysis: A Case Report and Literature Review

Abstract

Glomerular diseases with organized deposits can be classified into various etiologies. A diagnostic algorithm based on clinical and pathological findings has been proposed. However, some cases cannot be diagnosed using existing algorithms. Here, we report the case of a 77-year-old man diagnosed with membranoproliferative glomerulonephritis (MPGN) with striated ultrastructural deposits, micro-filament-like substructures with straight bands arranged in parallel in the subendothelial space by two sequential renal biopsies. His examinations and clinical findings were incompatible with known glomerular diseases with organized deposits. Dialysis was initiated 10 months after the second biopsy procedure. Furthermore, we report the first mass spectrometry analysis of laser micro-dissected glomeruli with striated ultrastructural deposits, which revealed significant levels of fibrinogen and fibronectin. Immunostaining was positive for fibrinogen, fibrin, and fibronectin in the subendothelial space. These findings suggest that the deposits were composed of a fibrin-fibronectin complex and that accumulation of these fibrin-fibronectin complexes possibly induced endothelial injury, leading to MPGN. We also reviewed the literature on the clinical and pathological characteristics of the four cases with striated ultrastructural deposits. Our investigation showed that all patients had the MPGN pattern and striated ultrastructural deposits in the subendothelial space, and all underwent hemodialysis within 3 years of renal biopsy. Clinicians should be aware of the findings of glomerulonephritis with striated ultrastructural deposits since this disease may be a new entity and has a poor prognosis.

Keywords: Deposit; Fibrin; Fibrinogen; Fibronectin; Mass spectrometry; Membranoproliferative glomerulonephritis.

Fig. 1.

Renal histological findings. a–c Partial mesangial and endocapillary hypercellularity and double-contour formation were shown in the first biopsy (periodic acid-Schiff stain (a), periodic acid-methenamine-silver stain (b), Masson’s trichrome stain (c)). d–f Immunofluorescence revealed focal granular staining of IgM, C3, and fibrinogen in the mesangium and along the capillary wall. g–i Electron microscopy showed foot process effacement and organized deposits with striated ultrastructural deposits in the subendothelial space. The electron-dense bands were 10–12 nm wide and 20–30 nm from center to center. j–l Immunohistochemical staining for fibrin, fibronectin, and fibrinogen were all positive in subendothelial space. m–o The second biopsy revealed global mesangial and endocapillary hypercellularity and double-contour formation in almost all glomeruli (periodic acid-Schiff stain (m), periodic acid-methenamine-silver stain (n), Masson’s trichrome stain (o)). p–r EM from the second biopsy revealed marked expansion of the area occupied by the striated ultrastructural deposits. a–f, j–o Bars = 50 μm. g, p Bars = 10 μm. h Bar = 2 μm. q Bar = 5 μm. i, r Bars = 500 nm.

Fig. 2.

Mass spectrometry (MS) data. We present MS data in our case (a) and an additional case (case 1) (b). The MS result of the additional case was provided by National Hospital Organization Kyoto Medical Center. Each number of the right-most column corresponds to the number of tandem MS spectra associated with the protein in the samples, which is a surrogate measure of abundance. Proteins with five or more spectra were used for clinical interpretation. Fibrinogen and fibronectin were detected at high levels in both cases. Furthermore, we estimated the absolute protein amount by emPAI, which confirmed that fibrinogen and fibronectin are significantly detected.

Fig. 3.

A diagnostic algorithm for glomerular diseases with organized deposits.