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Kidney non-tumor

Primary glomerular diseases

Membranous glomerulonephritis


Reviewers: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 25 February 2014, last major update July 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● Most common cause of nephrotic syndrome in adults (40%); 5% of cases in children
● Diffuse glomerular wall thickening due to in situ immune complexes (electron dense) in glomerular basement membrane but NOT in mesangium

Pathophysiology
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● 75% of adult and 20% of childhood cases are idiopathic autoimmune disease linked to HLA, caused by antibodies to a renal autoantigen (including α-enolase, J Proteomics 2011;74:2008 and others, Proteomics Clin Appl 2011;5:90)
● Considered the human model of Heymann nephritis, which in rats is produced by antibody to megalin antigen complex on basal surface of visceral epithelial cells (megalin is homologous to LDL receptor)
● Secondary cases are associated with cancer (lung, colon, melanoma), hepatitis B/C, malaria, schistosomiasis, drugs (penicillamine, captopril, gold, NSAID), heavy metals, lupus, diabetes, thyroiditis and angiofollicular lymph node hyperplasia (Arch Pathol Lab Med 1979;103:591)
● Proteinuria may be due to C5b-C9 (MAC complex of complement)
● Allograft recurrences represent idiopathic MGN due to IgG4, with different pathogenic mechanism than de novo MGN (Transplant Proc 2011;43:3743)

Clinical features
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● Insidious onset of nephrotic syndrome, occasionally hematuria and hypertension
● Must rule out and treat secondary causes
● 10% die or develop renal failure in 10 years (40% eventually develop renal failure)
● Rarely, tubulointerstitial nephritis due to anti-tubular basement membranes
● Hepatitis B cases resemble lupus nephritis class V, but are HepB+ and lack SLE’s extrarenal manifestations and autoantibodies (Mod Pathol 2000;13:166)

Variants of membranous glomerulonephritis (MGN):
● MGN with crescents
● MGN with antitubular basement membrane nephritis
● Transplant associated MGN
● MGN with superimposed renal vein thrombosis

Treatment
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● Variable course of disease makes it difficult to evaluate therapy
● Alternating steroids and chlorambucil or cyclophosphamide (Ponticelli protocol) for six months
● If no remission after protocol, consider cyclosporine, adrenocorticotropic hormone, mycophenolate mofetil, rituximab (J Biol Regul Homeost Agents 2012;26:135)
● Treatment is effective on post-transplant recurrences (Am J Transplant 2012;12:1029)

Case reports
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● 22 year old man with acute renal failure caused by Hodgkin's lymphoma (Ren Fail 2011;33:363)
● 24 year old woman with tuberculous peritonitis (J Infect Dev Ctries 2011;5:550)
● 27 year old man with syphilis (Nefrologia 2011;31:372)
● 43 year old man with C1q deposits followed by development of psoriasis (Nefrologia 2012;32:228)
● 45 year old woman with HIV infection and features of lupus nephritis (Lupus 2012;21:900)
● 55 year old man with pulmonary embolism (Case Report Med 2010;32:649)
● 60 year old woman with severe ankylosing spondylitis (Ann Pharmacother 2011;45:e62)
● HIV+ man (HJ Infect Public Health 2012;5:207)

Micro description
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● Early biopsies may be normal
● Later: uniform diffuse capillary wall thickening without hypercellularity, without mesangial sclerosis and without inflammatory cells
● Proximal convoluted tubules contain hyaline droplets, reflecting protein reabsorption
● With progression, get membrane thickening, narrow capillary lumina, mesangial sclerosis and glomerulosclerosis

Micro images
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Various images, including EM

       
Thickened glomerular capillary loops

       
Various images of fluourescence microscopy based on Hollande's fixative


Silver stain shows basement membrane spikes


Early stage MN on Silver stain


Rigid capillary tufts with visible fuchsinophilic deposits


Spikes and holes in MN on Silver stain

Immunofluorescence
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● Granular diffuse peripheral deposits, usually IgG and C3, also C5b-C9 and occasionally IgM or IgA
● C4d immunostaining may be diagnostic (Histol Histopathol 2011;26:1391)

Stages:
Stage I: LM - normal or slightly thickened BM, slight GMB vacuolization; IF - fine granular IgG, C3; EM - scattered small subepithelial electron dense deposits, no foot process effacement or spikes
Stage II: LM - moderately thickened BM with spikes and vacuolization; IF - moderate sized, granular IgG, C3; EM - diffuse spikes due to subepithelial deposits, diffuse foot process effacement
Stage III: LM - markedly thickened GBM, residual spikes and vacuoles, chain like appearance; IF - coarsely granular IgG, C3; EM - intramembranous deposits, spikes, neomembrane formation and diffuse foot process effacement
Stage IV: LM - markedly thickened GBM, few spikes, vacuoles and glomerulosclerosis; IF - focal IgG, C3; EM - sclerotic GBM, few deposits and lacunae

Immunofluorescence images
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Granular capillary loop staining for IgG in an idiopathic MN


Granular capillary loop staining for IgG in a lupus MN on IF


Diffuse granular immunofluoresence for IgG

Virtual slides
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Membranous glomerulonephritis

Electron microscopy images
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Intramembranous deposits


Stage I with electron dense deposits along glomerular basement membrane


Hepatitis B with subepithelial and mesangial electron dense deposits (M) and fusion of epithelial foot processes (arrows)


Subepithelial deposits in idiopathic MN


Subepithelial deposits in lupus MN

End of Kidney non-tumor > Primary glomerular diseases > Membranous glomerulonephritis

Ref Updated: 5/29/12


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