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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)? - PowerPoint PPT Presentation
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What are MPGN/DDD/C3G – what your kidney biopsy tells us
Dr Daniel GaleConsultant 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
Aviva medical encyclopaedia
The kidney biopsy
Walker et al Mod Path 2004
10-30 out of 1 million glomeruli are looked at
How are biopsies examined?
“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
Walker et al Mod Path 2004
A normal glomerulus – light microscopy
www.unckidneycenter.org
Aviva medical encyclopaedia
The normal glomerulus
Pierre Russo MD
Supporting cells
Blood
Urine
Urine
“Electron microscopy”
The tubules
Glomeruli
Tubules
Glomerulus
Tubule
Scarred area
Tubules disappear when the kidney is damagedNormal kidney
What do we see in MPGN/DDD/C3 glomerulopathy?
www.unckidneycenter.org http://library.med.utah.edu
“Tram tracks”
These appearances are defined as MPGNNormal
Electron dense deposits in MPGN and C3GN
www.unckidneycenter.org
Electron dense deposits can also be
seen in the outside of the membrane
Electron dense deposits on inside of membrane
Supporting cells creep into membrane
Normal capillary loop
Dense Deposit Disease
Compare with MPGN
Normal capillary loop www.unckidneycenter.org
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
DDD C3GN
MPGNAntibodies and complement deposited
Complement but no antibodies deposited
How are these diseases classified?
C3 glomerulopathies
Complement links MPGN, DDD and C3 glomerulopathy
Y Y
Y
Antibody production
Alternative Pathway
Terminal PathwayC3
Damage to kidney (MPGN)
Complement Factor H (CFH)Complement Factor I
Regulators
C1q
CFHRs
C5Classical Pathway
YC3NeF antibody X
YYY
Infection or autoimmune disease
CFHRs
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?