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?