Kidney nontumor
Primary glomerular diseases
Membranoproliferative glomerulonephritis

Author: Nikhil Sangle, M.D. (see Authors page)

Revised: 11 July 2018, last major update May 2012

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Membranoproliferative glomerulonephritis [title] "loattrfree full text"[sb]

Cite this page: Sangle, N. Membranoproliferative glomerulonephritis. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneymembranoprolif.html. Accessed July 20th, 2018.
Definition / general
  • Also called hypocomplementemic (C3), lobular or mesangiocapillary / mesangiopathic glomerulonephritis
  • Pattern of injury with alterations in basement membrane and proliferation of mesangial cells, due to subendothelial and mesangial deposition of immunoglobulins, caused by persistent antigenemia or circulating immune complexes
  • Either immunoglobulin mediated or complement mediated (although all types stain for C3)
  • Immunoglobulin mediated: due to chronic infections, autoimmune diseases, monoclonal gammopathy / dysproteinemias
  • Complement mediated: due to subendothelial and mesangial deposition of complement from dysregulation of alternative pathway; includes dense deposit disease (membranoproliferative glomerulonephritis type 2) and proliferative glomerulonephritis with C3 deposits; due to genetic mutations or development of autoantibodies to complement (Semin Nephrol 2011;31:341)
  • Intermittent remissions but overall downhill course
  • Diagnosis of MPGN I or MPGN II reduces overall primary allograft survival compared with other forms of glomerulonephritis (10 year graft survival drops from 65% to 56%, Am J Kidney Dis 2011;57:291)
Case reports
Microscopic (histologic) images

Images hosted on other servers:

Type I and type II (text and images)

Differential diagnosis
Type I: classical
Definition / general:
  • 5% of cases of glomerulonephritis affecting children and young adults; 2/3 of membranoproliferative glomerulonephritis cases
  • Immune complex deposition and activation of classical and alternative complement pathway
  • Typically presents with nephrotic syndrome and hypertension in patients 8 - 16 years old; less commonly nephritis
  • Also associated with Staphylococcus epidermidis infection with ventriculoatrial or ventriculojugular shunts
  • 2/3 have persistent decrease in serum C3 due to its hypercatabolism; also reduction in total hemolytic complement (CH) 50 levels and borderline / reduced levels of C1q, C4 and properdin
  • Secondary disease occurs with chronic immune complex disorders (SLE, hepatitis B / C, HIV, schistosomiasis), alpha-1-antitrypsin deficiency and malignancies
  • May cause high rates of nondiabetic end stage renal disease in Navajo Indians in US (Arch Pathol Lab Med 1989;113:158)


Case reports:
  • 16 year old girl with refractory disease and dramatic response to eculizumab, a monoclonal antibody to C5 (N Engl J Med 2012;366:1165)


Treatment:

Microscopic (histologic) description:
  • Large glomeruli with accentuation of lobules
  • Irregular thickening of glomerular basement membrane by interposition of mesangial cells between endothelium and basement membrane
  • Causes tram track / double contour appearance (PAS or silver stain), crescents in 20%
  • Neutrophils often present
  • May have hyaline aggregates of immune complexes in capillary lumina


Microscopic (histologic) images:

Images hosted on PathOut server:

C3 with mesangial rings on IF

Irregularly granular
capillary loop and
mesangial staining

Membranoproliferative lesions on PAS

Membrano-
proliferative lesions
on silver stain

Mesangioendocapillary
proliferation with
mesangial nodular
sclerosis



Images hosted on other servers:

Series of images including immunofluorescence and EM

Hypercellular glomeruli with accentuated lobules



Immunofluorescence (IF):
  • Lumpy bumpy (granular) for C3, IgG, early complement (C1q, C4); pattern is mesangial and subendothelial


Electron microscopy description:
  • Subendothelial and mesangial electron dense deposits, increased mesangial matrix, mesangialization of capillary loops and foot process fusion


Electron microscopy images:

Images hosted on PathOut server:

Subendothelial deposits

Subendothelial deposits with cellular interposition



Images hosted on other servers:

Splitting and reduplication of basement membrane

Large subendothelial electron dense
deposit along glomerular basement
membrane



Type II: dense deposit
Definition / general:
  • Essential diagnostic feature is not the membranoproliferative pattern but the presence of electron dense transformation of the glomerular basement membranes
  • Occurs in 1/3 of cases of membranoproliferative glomerulonephritis but some authors believe this entity is actually distinct from membranoproliferative glomerulonephritis (Mod Pathol 2007;20:605)
  • Familial or associated with partial lipodystrophy (loss of subcutaneous fat from fat and upper body)
  • Associated with uncontrolled activation of alternative complement pathway because of C3 nephritic factor (stabilizes C3 convertase; promotes C3 degradation)
  • Tends to present with nephritis more than nephrotic syndrome
  • Poorer prognosis than type I; 50% have renal failure in 10 years; 80 - 100% recur after renal transplant
  • Also deposits in basement membranes of spleen, choroid and Bruch membrane of retina
  • Rarely abnormalities in factor H (Hum Pathol 2011;42:1305, Iran J Kidney Dis 2012;6:149)


Microscopic (histologic) description:
  • Similar to type I but less prominent cellular proliferation
  • Eosinophilic, refractile and ribbon-like thickening of glomerular basement membrane and basement membrane of Bowman capsule and tubules
  • Strongly PAS+, stains red with trichrome but dense deposits are negative with silver stain


Microscopic (histologic) images:

Images hosted on PathOut server:

Mesangioendocapillary proliferation with lobular accentuation



Images hosted on other servers:

Type II



Immunofluorescence (IF):
  • Linear or double contoured C3 and properdin staining of glomerular capillary walls and bright nodular or ring-like reaction in mesangium, NOT in dense deposits
  • C3 staining also in mesangium, Bowman capsule and tubular basement membranes
  • Usually no immunoglobulins


Electron microscopy description:
  • Dense deposits in lamina densa of glomerular basement membrane, Bowman capsule; causes long ribbon of hazy material
  • Also nodular deposits of similar material in mesangium


Electron microscopy images:

Images hosted on other servers:

Ribbon-like dense
deposits within
glomerular basement
membrane



Additional references:
Type III: mixed
Definition / general:
  • Two rare morphologic subtypes (Burkholder and Anders) that are clinically similar to each other and to type I membranous glomerulonephritis
Type III: Burkholder variant
Definition / general:
  • Combined features of type I membranoproliferative glomerulonephritis and membranous glomerulonephritis
  • Associated with hepatitis C and HIV coinfection (J Am Soc Nephrol 1999;10:1566)


Microscopic (histologic) images:

Images hosted on other servers:

Series of images including immunofluorescence and EM



Electron microscopy description:
  • Subendothelial and subepithelial deposits and mesangial interposition associated with basement membrane spikes
Type III: Anders variant
General:
  • Hybrid of type I and II membranoproliferative glomerulonephritis


Electron microscopy description:
  • Massive accumulation of deposits within basement membrane with membranous disruption, highlighted by silver stain