Kidney nontumor / medical renal

Glomerular disease

Membranous nephropathy

Primary membranous nephropathy



Last author update: 21 March 2022
Last staff update: 21 March 2022

Copyright: 2003-2023, PathologyOutlines.com, Inc.

PubMed Search: Primary membranous nephropathy[TIAB] review[PT]

Ana Belén Larqué, M.D., Ph.D.
Page views in 2022: 8,537
Page views in 2023 to date: 804
Cite this page: Larqué AB. Primary membranous nephropathy. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneymemgn.html. Accessed January 28th, 2023.
Definition / general
Essential features
  • Idiopathic autoimmune glomerular disease
  • Nephrotic syndrome
  • Thickening of glomerular basement membrane and subepithelial deposition of immune complexes (silver stain, spike)
  • Anti-PLA2R autoantibodies
Terminology
  • Membranous glomerulopathy
  • Membranous glomerulonephritis
ICD coding
  • ICD-10:
    • N00-N08 - glomerular diseases
    • N00.2 - acute nephritic syndrome with diffuse membranous glomerulonephritis
    • N03.2 - chronic nephritic syndrome with diffuse membranous glomerulonephritis
Epidemiology
Sites
  • Kidney (glomerular disease)
Pathophysiology
  • Circulating autoantibodies bind to an autoantigen on the surface of the podocytes resulting in in situ immune complex formation that activates the lectin complement pathway and causes podocyte injury and proteinuria
  • 2 major target antigens are now firmly recognized: the M type phospholipase A2 receptor 1 (PLA2R) (~70%) and the thrombospondin type 1 domain containing 7A (THSD7A) (2 - 5%) (J Am Soc Nephrol 2017;28:421)
Etiology
  • Idiopathic autoimmune disease with a predisposition to autoimmunity conferred by HLA genes and an environmental trigger (J Am Soc Nephrol 2013;24:525)
Clinical features
  • Nephrotic syndrome
  • 20% with nonnephrotic proteinuria
  • Less frequent: hematuria (usually microscopic), hypertension, thrombotic and thromboembolic events (Clin J Am Soc Nephrol 2017;12:983)
Diagnosis
  • Nephrotic syndrome with serum anti-PLA2R antibody (Clin J Am Soc Nephrol 2017;12:983)
  • Demonstration of subepithelial deposition of immune complexes by renal biopsy and immunofluorescence
  • Positive PLA2R staining in glomeruli by immunohistochemistry
Laboratory
  • Positive serum anti-PLA2R antibody
  • High antibody levels (before and after treatment) correlate with proteinuria, response to therapy and (after therapy) long term outcomes (Clin J Am Soc Nephrol 2017;12:983)
Prognostic factors
Case reports
Treatment
Microscopic (histologic) description
Microscopic (histologic) images

Contributed by Ana Belén Larqué, M.D., Ph.D.

Glomerular basement membrane thickened

Subepithelial spikes


Granular staining for IgG4

Granular staining for PLA2R

Immunofluorescence description
Immunofluorescence images

Contributed by Ana Belén Larqué, M.D., Ph.D.

Granular staining for IgG



Images hosted on other servers:
Missing Image

Diffuse granular
immunofluoresence
for IgG

Positive stains
Electron microscopy description
Electron microscopy images

Contributed by Ana Belén Larqué, M.D., Ph.D. and Jonathan E. Zuckerman, M.D., Ph.D.

Subepithelial deposits

Intramembranous deposits

Membranous nephropathy, stage I


Membranous nephropathy, stage II

Membranous nephropathy, stage III

Membranous nephropathy, stage IV



Images hosted on other servers:
Missing Image

Intramembranous deposits

Genetics
Sample pathology report
  • Right kidney, biopsy:
    • Membranous nephropathy; minimal chronic changes (see comment)
      • Adequacy: adequate (cortex 85%, medulla 15%)
      • Microscopic description: 18 glomeruli, 1 of these with global sclerosis. Thickening of the glomerular capillary wall. Presence of spikes and internal vacuolizations of the glomerular basement membrane evaluated by silver stain. No evidence of hypercellularity, crescent or necrosis. Fibrosis occupying < 10% of the interstitium.
      • Immunofluorescence microscopy:
        • Number of glomeruli: 4
        • Diffuse granular staining of the glomerular basement membrane for IgG (+++) and C3 (++); there were no deposits of IgA, IgM, C1q or fibrin.
      • Immunohistochemistry: diffuse and strong granular positivity of glomerular basement membrane for PLA2R and IgG4
      • Comment: positivity for anti-PLA2R and IgG4 favor the diagnosis of primary membranous glomerulopathy
Differential diagnosis
Board review style question #1

Which of the following is true about primary membranous nephropathy?

  1. Active periglomerular inflammation and rupture of Bowman capsule
  2. Little or no immunoglobulin or complement deposits by immunofluorescence
  3. Most common cause of idiopathic nephrotic syndrome in nondiabetic adults worldwide
  4. Significant mesangial or endocapillary hypercellularity
Board review style answer #1
C. Most common cause of idiopathic nephrotic syndrome in nondiabetic adults worldwide

Comment Here

Reference: Primary membranous nephropathy
Board review style question #2

Which of the following findings favors primary membranous nephropathy over secondary forms?

  1. Glomerular basement membrane spikes by PAS and silver stains
  2. Intense global and granular PLA2R and IgG4 staining of glomerular basement membrane
  3. Nephrotic range proteinuria
  4. Thickening of the glomerular capillary wall
Board review style answer #2
B. Intense global and granular PLA2R and IgG4 staining of glomerular basement membrane

Comment Here

Reference: Primary membranous nephropathy
Back to top
Image 01 Image 02