Renal Digest
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    Fibrillary glomerulonephritis
     Key features:
 
Clinical: Variable presentation, but patients often have nephrotic-range proteinuria; the disease is invariably progressive
Clinical: Variable presentation, but patients often have nephrotic-range proteinuria; the disease is invariably progressive
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
Light microscopy: Diverse histologic patterns, most commonly membranoproliferative or mesangioproliferative; Congo red stain is negative
Light microscopy: Diverse histologic patterns, most commonly membranoproliferative or mesangioproliferative; Congo red stain is negative
Immunofluorescence: Polyclonal IgG reactivity
Immunofluorescence: Polyclonal IgG reactivity
Immunofluorescence: Polyclonal IgG reactivity
Electron microscopy: Randomly arranged, non-branching fibrils, 12-30 nm in diameter
Electron microscopy: Randomly arranged, non-branching fibrils, 12-30 nm in diameter
Electron microscopy: Randomly arranged, non-branching fibrils, 12-30 nm in diameter


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.
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.
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
Fibrillary glomerulopathy
Fibrillary glomerulopathy

Differential diagnosis:
Immunoglobulin A (IgA) nephropathy, mesangioproliferative type
Lupus nephritis, mesangioproliferative type (class II)
Membranoproliferative glomerulonephritis (MPGN), idiopathic, type I
Monoclonal immunoglobulin deposition disease (MIDD)
Immunotactoid glomerulopathy
Amyloidosis

Etiology:  
Unclear etiology; fibrillary GN is only rarely associated with B-cell neoplasias while the link is stronger in cases of immunotactoid glomerulopathy {1}
Unclear etiology; fibrillary GN is only rarely associated with B-cell neoplasias while the link is stronger in cases of immunotactoid glomerulopathy {1}
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
Occurs more commonly in older patients (very rare in children) and Caucasians
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
There is usually nephrotic range proteinuria; other presenting symptoms vary, including nephrotic syndrome, acute renal failure, rapidly progressive nephritis, chronic renal insufficiency
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}
Outcome may be dependent on histologic pattern of injury {2}
Outcome may be dependent on histologic pattern of injury {2}

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}
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}
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
Proliferative changes, such as increased endocapillary proliferation or crescent formation, are uncommon but occur
Proliferative changes, such as increased endocapillary proliferation or crescent formation, are uncommon but occur
Congo red stain is negative
Congo red stain is negative
Congo red stain is negative
Silver stain may reveal “moth eaten” appearance (non-reactive deposits admixed with reactive matrix)
Silver stain may reveal “moth eaten” appearance (non-reactive deposits admixed with reactive matrix)
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
Visceral epithelial cells: Focal, sometimes marked effacement of visceral epithelial cell foot processes
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 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 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
Glomerular endothelial cells: Show loss of fenestrations and other non-specific changes; they do not contain tubuloreticular structures
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
Mesangium: Usually expanded by matrix and organized fibrillary deposits
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 that present with nephrotic syndrome: Membranous nephropathy, amyloidosis, idiopathic focal and segmental glomerulosclerosis
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
Diseases with acute renal failure and rapidly progressive nephritis: Crescentic glomerulonephritides
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)
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)
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
Chronic thrombotic angiopathies
Chronic thrombotic angiopathies
Diabetic glomerulosclerosis
Diabetic glomerulosclerosis
Diabetic glomerulosclerosis
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Fibrillary glomerulopathy, with marked mesangial expansion and mildly increased cellularity. Some of the loops are thickened; H&E, 200x
Fibrillary glomerulopathy; marked mesangial expansion and thickening of some loops; H&E, 400x
Fibrillary glomerulopathy superimposed to advanced diabetic glomerulosclerosis; fibrillary deposits are seen in very expanded mesangium; EM, 25,000
Fibrillary glomerulopathy, EM, 20,000x
Low power electronmicrograph of fibrillary glomerulopathy; the deposits are present in the mesangium, while capillary loops are spared, EM, 2,000x
Mesangial deposits in fibrillary glomerulopathy, EM, 4,000x
Intramembranous and subepithelial fibrillary deposits in fibrillary glomerulopathy; EM, 4,000x
High power view of fibrillary GN; EM, 44,000x
Fibrillary glomerulopathy, with deposits made of non-branching, randomly arranged fibrils; EM, 50,000x
Capillary loop involvement in fibrillary glomerulopathy; EM, 6000x
Capillary loop involvement in fibrillary glomerulopathy; EM, 8,000x
Fibrillary glomerulopathy, with mesangial expansion and thickening of some loops. There is prominence of glomerular epithelial cells in some parts of the tuft; JMS stain, 200x
Cellular crescent in fibrillary glomerulonephritis; JMS stain, 200x
Fibrillary glomerulopathy; trichrome, 200x
Fibrillary glomerulonephritis, low power view; mesangial expansion, increased cellularity, and a cellular crescent in a single glomerulus; PAS, 100x
Fibrillary glomerulonephritis; there is a cellular crescent and segmental hypercellularity due to inflammatory infiltrate; PAS, 200x
Marked mesangial expansion and mild mesangial hypercellularity in fibrillary glomerulopathy; PAS, 400x
Thickened capillary loops and prominent mesangium in fibrillary glomerulopathy; JMS, 400x
Fibrillary glomerulopathy; PAS, 200x
Thickened capillary loops, expanded mesangium, and mesangial hypercellularity in fibrillary glomerulopathy; PAS, 400x
Fibrillary glomeruopathy; PAS, 400x
Negative Congo red stain in fibrillary glomerulopathy; Congo red, 400x
Fibrillary glomerulopathy; JMS, 100x
Fibrillary glomerulopathy, low magnification; PAS, 100x
Mesangial reactivity for IgG in fibrillary GN; IF, 200x
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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