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

Aviva medical encyclopaedia The kidney biopsy Walker et al Mod Path 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 Aviva medical encyclopaedia

The normal glomerulus Pierre Russo MD Supporting cells Blood Urine “Electron microscopy”

The tubules Glomeruli Tubules Glomerulus Tubule Scarred area Tubules disappear when the kidney is damaged Normal kidney

What do we see in MPGN/DDD/C3 glomerulopathy? “Tram tracks” These appearances are defined as MPGN Normal

Electron dense deposits in MPGN and C3GN 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

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 MPGN Antibodies 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 Pathway C3 Damage to kidney (MPGN) Complement Factor H (CFH) Complement Factor I Regulators C1q CFHRs C5 Classical Pathway Y C3NeF antibody X Y Y Y 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?