Kidney nontumor
Glomerular disease
Membranoproliferative glomerulonephritis (MPGN) and complement related diseases
Dense deposit disease

Editorial Board Member: Nicole K. Andeen, M.D.
Editor-in-Chief: Debra Zynger, M.D.
Ana Belén Larqué, M.D., Ph.D.

Topic Completed: 24 September 2020

Minor changes: 24 September 2020

Copyright: 2020, PathologyOutlines.com, Inc.

PubMed Search: Dense deposit disease [title] pathology

Ana Belén Larqué, M.D., Ph.D.
Page views in 2020 to date: 102
Cite this page: Larqué AB. Dense deposit disease. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/kidneydensedepdisease.html. Accessed September 30th, 2020.
Definition / general
Essential features
  • Rare C3 related glomerulonephritis affecting mostly children and older people
  • Clinical syndrome of glomerulonephritis with low level of serum C3, related to abnormalities of alternative complement pathway
  • Varied glomerular pathology by light microscopy with predominant C3 and little or no immunoglobulin deposition by immunofluorescence
  • Hyperdense intramembranous deposits in the glomerular basement membrane by electron microscopy (pathognomonic)
  • Recurs in almost all renal allografts
Terminology
  • Membranoproliferative glomerulonephritis, type II
ICD coding
  • ICD-10: N00-N08 - glomerular diseases
Epidemiology
Sites
  • Kidney (glomerular disease)
Pathophysiology
  • Chronic activation of alternative complement pathway by precipitant factors / autoantibodies / genetic predisposition, resulting in the accumulation of complement components in the tissue, recruitment of leukocytes and inflammatory damage of glomerulus (Pediatr Nephrol 2017;32:43)
Etiology
  • Autoantibodies: C3 nephritic factor, autoantibodies to complement factor H, factor B or C3
  • Genetic predisposition in complement component genes: CFH, CFI, C3, CFHR5 and factor H
  • Precipitating factors: infection, post chemotherapy for breast cancer, monoclonal gammopathy
  • Reference: Clin Exp Nephrol 2017;21:541
Clinical features
Diagnosis
  • Clinical syndrome of glomerulonephritis
  • Light microscopy: varied glomerular pathology
  • Immunofluorescence microcsopy: C3 dominant glomerular staining and little or no immunoglobulin deposition (C3 staining intensity ≥ 2 orders of magnitude more than any other immune reactant on a scale of 0 - 3+) (Kidney Int 2013;84:1079)
  • Electron microscopy: hyperdense intramembranous deposits in the glomerular basement membrane (pathognomonic)
Laboratory
Prognostic factors
Case reports
Treatment
Microscopic (histologic) description
  • Varied glomerular pathology (Mod Pathol 2007;20:605):
    • Mesangial proliferation (30 - 50%)
    • Membranoproliferative glomerulonephritis (25 - 45%)
    • Acute exudative glomerulonephritis (10 - 20%)
    • Crescentic glomerulonephritis (10 - 20%)
Microscopic (histologic) images

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

Glomeruli with membranoproliferative pattern

  

Glomerulus with mesangial pattern

Glomerular basement membrane thickening

Double contour capillary walls

Immunofluorescence description
  • Predominant C3 staining (ribbon-like [garland] pattern) in glomerular basement membranes with or without railroad track or double contour pattern along glomerular basement membranes; coarse mesangial spherules or ring-like deposits
  • Focal Ig deposits in minority (almost always 2 levels of fluorescence intensity less than C3)
  • Reference: Colvin: Diagnostic Pathology - Kidney Diseases, 2nd Edition, 2015
Immunofluorescence images

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

Granular C3 deposits

Positive stains
Electron microscopy description
  • Accumulation in the glomerular basement membrane of uniquely electron dense material in a continuous, elongated, ribbon-like pattern or in small nodular aggregates within the irregularly thickened lamina densa; these dense deposits usually involve long segments of basement membrane but occasionally only a few loops are involved (sausage string pattern)
  • Same type of deposit is characteristically also present in the mesangium, Bowman capsule, tubular basement membranes and occasionally in the walls of arterioles and peritubular capillaries
  • Similar dense deposits have been noted in splenic sinusoidal basement membranes and in the eye involving the choriocapillaris basement membranes and Bruch membrane
  • Podocyte injury eventually occurs
  • Reference: Dickersin: Diagnostic Electron Microscopy - A Text/Atlas, 2nd Edition, 2000
Electron microscopy images

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

Linear electron dense deposits

Genetics
Videos

Membranoproliferative GN

Sample pathology report
  • Right kidney, biopsy:
    • Dense deposit disease with C3 membranoproliferative glomerulonephritis pattern
    • Adequacy: adequate (cortex 80%, medulla 20%)
    • Microscopic description:
      • 23 glomeruli, 4 of these with global sclerosis
      • Majority of glomeruli showed a diffusely thick glomerular basement membrane and mesangial hypercellularity with increased mesangial matrix
      • Some glomerular basement membrane showed double contour
      • Fibrosis occupying 15% of the interstitium with minimal lymphoplasmacytic infiltrate
    • Immunofluorescence microscopy:
      • Number of glomeruli: 4
      • All glomeruli showed granular C3 (+++) deposits in mesangium and capillary walls
      • There were no deposits of IgA, IgM, IgG, C1q or fibrin
    • Ultrastructural study:
      • A glomerulus was evaluated that showed a preserved general structure with thickening of the basement membranes due to deposits in the lamina densa of glomerular basement membrane
      • These deposits were extensive, of different thickness and showed a very electron dense appearance
    • These morphological findings are characteristic of dense deposit disease
Differential diagnosis
Board review style question #1

Which of the following is true about dense deposit disease?

  1. Predominant IgG staining by immunofluorescence
  2. Recurs in almost all renal allografts
  3. Spontaneous remissions are common
  4. There is universally effective treatment
  5. Ultrastructural findings are not specific
Board review answer #1
B. Recurs in almost all renal allografts

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Reference: Dense deposit disease
Board review style question #2
The final diagnosis of dense deposit disease is established based on

  1. Clinical symptoms alone
  2. Combination of clinical symptoms and light microscopy
  3. Electron microscopy
  4. Light microscopy alone
  5. Low C3 levels alone
Board review answer #2
C. Electron microscopy

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Reference: Dense deposit disease
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