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1. Infection Related Glomerulopathy
Introduction – Rapid Overview
Mohammed Abdel Gawad
Nephrology Specialist
Alexandria – EGY
drgawad@gmail.com
Mansoura University – September 2014

3. At the beginning of the last century:
Postulated that the disease resulted
from antibodies that instead of having
beneficial effects were pathogenic, an
insight that constitutes a landmark
that opened the field of immune-mediated
renal disease.1
Clemens von Pirquet

5. • Post-streptococal GN
• Endocarditis associated GN
• Shunt nephritis

6. • Post-streptococal GN
• Endocarditis associated GN
• Shunt nephritis

7. Post-streptococcal Glomerulonephritis
Nephritogenic strains of group A Streptococcus pyogenes
Streptococcal
impetigo of M types
47, 49, 55, and 57
Throat infections with
streptococcus
types 1, 2, 4, and 12
4–6 weeks 7–15 days
Nephritis
Poynard T, Yuen MF, Ratziu V et al. Viral hepatitis C. Lancet 2003; 362:2095–2100.

8. Post-streptococcal Glomerulonephritis
Nephritogenic strains of group A Streptococcus pyogenes
Streptococcal
impetigo of M types
47, 49, 55, and 57
Throat infections with
streptococcus
types 1, 2, 4, and 12
4–6 weeks 7–15 days
Nephritis
Poynard T, Yuen MF, Ratziu V et al. Viral hepatitis C. Lancet 2003; 362:2095–2100.

9. Post-streptococcal Glomerulonephritis
Pathogenesis
Streptococcal
Infection
Streptococcal
proteinase
exotoxin B (SPEB)
Development of
circulating
immune complexes
Deposited
subendothelial and
mesangial locations
Initiate an inflammation
(local complement activation
and the recruitment of
neutrophils and monocytes
macrophages)
Cationic antigens or
dissociation of immune
complexes into the
outer aspect of the
glomerular basement
membrane

10. Post-streptococcal Glomerulonephritis
Pathogenesis
Streptococcal
Infection
Streptococcal
proteinase
exotoxin B (SPEB)
Nephritis-associated
plasmin
receptor (NAPLr)
A local direct mechanism of glomerular inflammatory damage
it is not co-localized with complement or immunoglobulin
Development of
circulating
immune complexes

11. Post-streptococcal Glomerulonephritis
Complement Activation
Low C3 / Normal or slightly low C4
NAPLr
C3Nef IgG
antibodies
in sera

12. Post-streptococcal Glomerulonephritis
Pathology
Diffuse endocapillary GN with proliferation
of mesangial and endothelial cells

13. Post-streptococcal Glomerulonephritis
Pathology
Glomerular immune deposits of C3
(100% of the cases), IgG (62%), IgM (76%)

14. Post-streptococcal Glomerulonephritis
Management

15. Post-streptococcal Glomerulonephritis
Management

16. Post-streptococcal Glomerulonephritis
Important Clinical Points
If decreased C3 levels lasted for more than a month (suggests
lupus or hypocomplementemic MPGN)
Mild proteinuria (<500 mg/day) and microscopic
hematuria may persist for up to 1 year

17. • Post-streptococal GN
• Endocarditis associated GN
• Shunt nephritis

18. Endocarditis-Associated Glomerulonephritis
Pathogenesis
Deposition of immune complexes containing
bacterial antigens in glomeruli, a mechanism
similar to that proposed for PSGN.

19. Endocarditis-Associated Glomerulonephritis
Complement Activation
Low C3 / low C4

20. Endocarditis-Associated Glomerulonephritis
Pathology
Less commonly: focal GN, MN, and MPGN type I may be found.

21. Endocarditis
Renal Presentation (other than GN)
Infective
Endocarditis
High Cr at presentation,
which improves on
antibiotics
Proteinuria/Hematuria
Low complement
+ve RF and cryoglobulins
GN
Increased Cr
over time with
antibiotic use
Acute interstitial
nephritis
Toxic ATN
Acute unilateral
flank pain /
frank hematuria
Renal emboli

22. Endocarditis-Associated Glomerulonephritis
Management

23. • Post-streptococal GN
• Endocarditis associated GN
• Shunt nephritis

24. Shunt Nephritis
Infected atrioventricular shunts; this
may occur 2 months to many years after
insertion
- S. Epidermidis and S. aureus
- Less frequently Propionibacterium acnes,
diphtheroids, Pseudomonas, or Serratia.
ventriculoperitoneal shunts are rarely
complicated with GN.

25. Shunt Nephritis
Complement Activation
Low C3 / low C4

26. Shunt Nephritis
Pathology
IgM, IgG, and C3 deposits are present in the glomerular capillary
and mesangium.

27. Shunt Nephritis
Management
prompt removal of the infected atrioventricular
shunt, which is usually replaced by
a ventriculoperitoneal shunt.

29. Viral Infection Related Glomerulopathy
General Pathogenesis
Pathogenetic
mechanisms
deposition
of
exogenous
immune
complexes
in situ
formation
of immune
complexes
autoantibody
formation
directed to
endogenous
antigen
modified by
viral injury
virus-induced release
of proinflammatory
cytokines, chemokines,
adhesion molecules,
and growth factors; and
direct cytopathic effects
of viral proteins

30. Hepatitis B Virus–Associated Renal
Disease
HBV & The
Kidney
Membranous
Nephropathy
MPGN
Mesangial
Proliferative
GN
Polyarteritis
Nodosa

31. Hepatitis B Virus–Associated Renal
Disease
HBV & The
Kidney
Membranous
Nephropathy
• MN may occur in chronic HBV carriers
Mesangial
• Nephrotic
Proliferative
Polyarteritis
MPGN
• Often have impaired Glomerulonep
renal function
Nodosa
• Clinically apparent liver hritis
disease
• C3 and C4 levels are decreased in 20% to 50%
• Mesangial immune deposits may also be
present

32. Hepatitis B Virus–Associated Renal
Disease
HBV & The
Kidney
Membranous
Nephropathy
MPGN
• Type 1 MPGN
• the most common glomerular
Mesangial
Proliferative
Glomerulonep
hritis
Polyarteritis
Nodosa
lesion in adult HBV carriers
• Cryoglobulinemia
• Chronic liver disease (may be
clinically asymptomatic)
• Nephrotic or non nephrotic
proteinuria, often associated
with microhematuria

33. Hepatitis B Virus–Associated Renal
Disease
HBV & The
Kidney
Membranous
Nephropathy
MPGN
Mesangial
Proliferative
GN
Polyarteritis
Nodosa
• IgA Deposits
• It is a consequence of chronic
liver disease with impaired
clearance of IgA circulating
immune complexes

34. Hepatitis C Virus–Associated Renal
Disease
HCV & The Kidney
MPGN
with or
without
cryoglobu
linemia
MN
fibrillary
GN
FSGS
(especially in
African
Americans)
TMA with
anticardiolipin
antibodies

35. Hepatitis C Virus–Associated Renal
Disease
HCV & The Kidney
MPGN
with or
without
cryoglobu
linemia
MN
fibrillary
GN
FSGS
(especially in
African
Americans)
TMA with
anticardiolipin
antibodies

36. Hepatitis C Virus–Associated Renal
Disease

37. Hepatitis C Virus–Associated Renal Disease
Complement Activation
Low C3 / low C4

38. MPGN Classification
According to TYPE of deposits
Algorithm source: Sanjeev Sethi et al. N Engl J Med 2012;366:1119-31.

39. MPGN Classification
According to TYPE of deposits
Algorithm source: Sanjeev Sethi et al. N Engl J Med 2012;366:1119-31.
No C3
no Ig
chronic
phase of
TMA

40. MPGN Classification
According to TYPE of deposits
Algorithm source: Sanjeev Sethi et al. N Engl J Med 2012;366:1119-31.
No C3
no Ig
chronic
phase of
TMA
Always check the possibility of Infection

42. Always suspect
infection whatever the
type of the deposits

44. Suspect any organism
as a cause of post
infectious MPGN
whenever there is an
evidence of infection

46. Thank You
Mohammed Abdel Gawad