Kidney nontumor
Primary glomerular diseases
Membranoproliferative glomerulonephritis

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

Revised: 25 September 2017, last major update May 2012

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

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

Cite this page: Sangle, N. Membranoproliferative glomerulonephritis. website. Accessed June 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)


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

proliferative lesions
on silver stain

proliferation with
mesangial nodular

Images hosted on other servers:

Series of images including immunofluorescence and EM

Hypercellular glomeruli with accentuated lobules

With hepatitis B related disease,
showing duplication of capillary
wall and tram track
appearance (silver stain)

Fluorescence microscopy shows
deposits corresponding to
immune complexes along
glomerular basement membrane

IgG in glomerular capillary loops

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

Foot processes of visceral epithelial cells show fusion

Large subendothelial electron dense
deposit along glomerular basement

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

Fluorescent ribbons of
variable thickness seen
along glomerular
capillary loops (arrows)

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

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
  • 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