Kidney nontumor
Glomerular disease
Membranous nephropathy
Primary membranous nephropathy
Author: Nikhil Sangle, M.D.
Topic Completed: 1 September 2014
Minor changes: 31 March 2021
Copyright: 2003-2021, PathologyOutlines.com, Inc.
PubMed Search: Membranous glomerulonephritis [title] "loattrfree full text"[sb]
Table of Contents
Definition / general | Pathophysiology | Clinical features | Treatment | Case reports | Microscopic (histologic) description | Microscopic (histologic) images | Immunofluorescence description | Immunofluorescence images | Electron microscopy images | Board review style question #1 | Board review style answer #1Cite this page: Sangle N. Primary membranous nephropathy. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneymemgn.html. Accessed June 19th, 2021.
Definition / general
- 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
- 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
- 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 antitubular 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
- 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
- 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)
- 54 year old woman with history of diabetes, presenting with nephrotic syndrome and found to have a 1 cm enhancing lower pole renal mass (Case of the Month #498)
- 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)
Microscopic (histologic) description
- 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
Microscopic (histologic) images
Rigid capillary tufts with visible fuchsinophilic deposits
Spikes and holes in MN on silver stain
Early stage MN on silver stain
Contributed by Nicole K. Andeen, M.D. (Case #498)
H&E
Jones stain
Images hosted on other servers:
Various images, including EM
Thickened glomerular capillary loops
Silver stain shows basement membrane spikes
Immunofluorescence description
- 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 for 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
Granular capillary loop staining for IgG in an idiopathic MN
Granular capillary loop staining for IgG in a lupus MN on IF
Contributed by Nicole K. Andeen, M.D. (Case #498)
Granular peripheral capillary wall staining for IgG
Images hosted on other servers:
Diffuse granular immunofluoresence for IgG
Electron microscopy images
Images hosted on Pathout server:
Subepithelial deposits in idiopathic MN
Subepithelial deposits in lupus MN
Images hosted on other servers:
Intramembranous deposits
Board review style question #1
What is the clinical utility of identifying anti-PLA2R antibodies in a patient with membranous nephropathy?
- It is characteristic of primary membranous nephropathy and evaluation for an underlying neoplasm or autoimmune disorder is not needed
- It suggests an underlying autoimmune disorder
- It suggests an underlying malignancy
- It supports a diagnosis of secondary membranous nephropathy
Board review style answer #1
A. It is characteristic of primary membranous nephropathy and evaluation for an underlying neoplasm or autoimmune disorder is not needed.
Comment Here
Reference: Primary membranous glomerulonephritis
Comment Here
Reference: Primary membranous glomerulonephritis
