What are MPGN/DDD/C3G – what your kidney
biopsy tells us
Dr Daniel Gale
Consultant Nephrologist
Introduction
• What is a kidney biopsy?
• How is it processed and looked at?
• What are the changes that lead to diagnosis of
MPGN or C3 glomerulopathy (DDD/C3GN)?
– How are these diseases classified?
• Why do these changes occur?
The biopsy procedure
Mrug and Bissler KI 2010
The kidney biopsy
Aviva medical
encyclopaedia
10-30 out of 1 million
glomeruli are looked at
Walker et al Mod Path 2004
How are biopsies
examined?
Walker et al Mod Path 2004
“Light microscopy”
• Fixed (pickled) in formalin
• Embedded in wax (paraffin)
• Sliced very thin (2 µm)
• Mounted on a slide
• Stained to show up cells and
proteins
Mrug and Bissler KI 2010
A normal glomerulus – light microscopy
www.unckidneycenter.org
Aviva medical encyclopaedia
The normal glomerulus
“Electron microscopy”
Urine
Blood
Urine
Supporting cells
Pierre Russo MD
The tubules
Normal kidney
Tubules
Tubules disappear when
the kidney is damaged
Tubule
Glomerulus
Glomeruli
Scarred
area
What do we see in MPGN/DDD/C3
glomerulopathy?
Normal
These appearances are
defined as MPGN
“Tram tracks”
www.unckidneycenter.org
http://library.med.utah.edu
Electron dense deposits in MPGN and C3GN
Normal capillary loop
Electron dense deposits on inside of membrane
www.unckidneycenter.org
Supporting cells creep into membrane
Electron dense
deposits can also be
seen in the outside of
the membrane
Dense Deposit Disease
Normal capillary loop
www.unckidneycenter.org
Compare with
MPGN
What is in these deposits?
• Special stains (“immuno”) reveals what they contain:
• Complement (C3) almost always present
• In MPGN (but not DDD/C3G) antibodies also present
How are these diseases classified?
MPGN
Antibodies and
complement
deposited
Complement but no
antibodies deposited
DDD
C3GN
C3 glomerulopathies
Complement links MPGN, DDD and C3
glomerulopathy
CFHRs
X
Regulators
C3NeF
antibody
Infection or
autoimmune
disease
Alternative
Pathway
Classical
Pathway
C1q
Antibody
production
Complement Factor H (CFH)
Complement Factor I
C5
C3
Terminal
Pathway
Damage to kidney
(MPGN)
Summary – what the kidney biopsy tells us
• What the disease is (MPGN, DDD or C3
glomerulonephritis)
• Whether this is likely to result from antibody
production (autoimmunity) or a change in a
complement regulating gene
• The amount of inflammation (number of cells) in
the kidney
• The amount of scarring in the kidney
Any questions?