| Fibrillary glomerulonephritis
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Key features:
 | Clinical: Variable presentation, but patients often have nephrotic-range proteinuria; the disease is invariably progressive | | Light microscopy: Diverse histologic patterns, most commonly membranoproliferative or mesangioproliferative; Congo red stain is negative | | Immunofluorescence: Polyclonal IgG reactivity | | Electron microscopy: Randomly arranged, non-branching fibrils, 12-30 nm in diameter |
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Definition:  | Fibrillary glomerulopathy is characterized by progressive clinical course, variable histologic patterns (most commonly membranoproliferative or mesangioproliferative), with extracellular deposition of Congo red negative material, ultrastructurally consisting of non-branching, randomly arranged microfibrils 12-30 nm in diameter, usually with polyclonal IgG4 immunofluorescence reactivity. |
Synonym: | Fibrillary glomerulopathy |
Differential diagnosis:
Etiology: | Unclear etiology; fibrillary GN is only rarely associated with B-cell neoplasias while the link is stronger in cases of immunotactoid glomerulopathy {1} |
Clinical: | Occurs more commonly in older patients (very rare in children) and Caucasians | | There is usually nephrotic range proteinuria; other presenting symptoms vary, including nephrotic syndrome, acute renal failure, rapidly progressive nephritis, chronic renal insufficiency | | Outcome may be dependent on histologic pattern of injury {2}. The disease is associated with significant risk of ESKD {3} |
Histopathology: | Commonly, there is mesangial expansion with increased mononuclear inflammatory cells and matrix and peripheral capillary loop thickening (MPGN-like pattern of injury); sometimes, the predominant pattern is mesangioproliferative (if the deposition is not involving capillary loops) or even less commonly, membranous, diffuse proliferative, or sclerosing patterns may be seen {2} | | Proliferative changes, such as increased endocapillary proliferation or crescent formation, are uncommon but occur | | Congo red stain is negative | | Silver stain may reveal “moth eaten” appearance (non-reactive deposits admixed with reactive matrix) |
Immunofluorescence:
There is polyclonal deposition of IgG (most often IgG1 or IgG4) and C3 in the mesangium and along the peripheral capillary loops; in less than 10% of cases, the reactivity will be of monoclonal IgG; in very rare cases there will be no immunoglobulin reactivity.
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Electron microscopy: | Visceral epithelial cells: Focal, sometimes marked effacement of visceral epithelial cell foot processes | | Glomerular basement membranes: Usually marked thickening of the membranes with extensive fibrillary deposits; the deposition extends to subepithelial, subendothelial, and paramesangial spaces. The fibrils are non-branching, randomly oriented, 12-30 nm in diameter | | Glomerular endothelial cells: Show loss of fenestrations and other non-specific changes; they do not contain tubuloreticular structures | | Mesangium: Usually expanded by matrix and organized fibrillary deposits |
Clinical differential diagnosis: | Diseases that present with nephrotic syndrome: Membranous nephropathy, amyloidosis, idiopathic focal and segmental glomerulosclerosis | | Diseases with acute renal failure and rapidly progressive nephritis: Crescentic glomerulonephritides |
Pathologic differential diagnosis: | Immune complex-mediated glomerulonephritides with MPGN-pattern of injury; these include idiopathic MPGN, autoimmune diseases (lupus class IV, MCTD, RA, SS, etc.) and chronic infections (hepatitis B and C, hepatitis C-related cryoglobulinemia, endocarditis, shunt infections, parasitic infections) | | Chronic thrombotic angiopathies | | Diabetic glomerulosclerosis |
|  Please click here to comment | | | References : | | 1. Bridoux F, Hugue V, Coldefy O, Goujon JM, Bauwens M, Sechet A, Preud´HommeJL, Touchard G. Fibrillary glomerulonephritis and immunotactoid (microtubular) glomerulopathyare associated with distinct immunologic features.Kidney Int. 2002 Nov;62(5):1764-75. PUBMED | | 2. Rosenstock JL, Markowitz GS, Valeri AM, Sacchi G, Appel GB, D´Agati VD. Fibrillary and immunotactoid glomerulonephritis: Distinct entities withdifferent clinical and pathologic features.Kidney Int. 2003 Apr;63(4):1450-61. PUBMED | | 3. PUBMED |
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