Evidence based treatment of MPGN based on latest KDIGO guidelines

1. TREATMENT
OF MPGN
What is the evidence?
by
Mohamed Essam

2. Before we start
• MPGN may be either 1ry or 2ry
• All patient should be treated with standard
supportive antiproteinuric and
antihypertensive measures including ACEi
and ARBs.
• 1ry MPGN incidence rate is declining as
reported by a systematic review of literature
published in NDT 2011 where it was found to
be 0.2/100,000 population/year.(1)

4. 1ry MPGN

5. KDIGO
www.kdigo.org

6. Kidney Disease: Improving Global Outcomes (2)
www.kdigo.org

7. Kidney Disease: Improving Global Outcomes
www.kdigo.org

8. Comprehensive clinical nephrology, 2010, P. 267-268
In Adults
Asymptomatic Nephrotic syndrome RPGN with
Non Nephrotic Or Impaired renal diffuse crescents
range proteinuria functions
Normal renal
functions Pulse steroids and
6m CST Cyclophosphamides
(Prednisone 1mg/kg BW/day) +/- plasmapheresis
No specific treatment +/- Cytotoxic drugs
Close FU / 3m
Considerable reduction If no response
of proteinuria within 3m
Continue CST at the Stop CST
minimal effective dose R with Cyclosp, Tac or MMF(3)

9. 1ry MPGN
• In children

10. 2ry MPGN
• Treatment of the cause.
• We will concentrate on HBV, HCV associated MPGN.

11. HBV Associated MPGN
Comprehensive clinical nephrology, 2010, P. 268
Kidney Disease: Improving Global Outcomes
www.kdigo.org

12. Kidney Disease: Improving Global Outcomes
www.kdigo.org

13. Kidney Disease: Improving Global Outcomes
www.kdigo.org

14. Kidney Disease: Improving Global Outcomes
www.kdigo.org

15. (4)

17. HCV Associated MPGN
and Cryoglobulinemia

18. Kidney Disease: Improving Global Outcomes
www.kdigo.org

19. Kidney Disease: Improving Global Outcomes
www.kdigo.org

20. HCV genotypes
HCV is classified into eleven major genotypes (designated 1-11), many
subtypes (designated a, b, c, etc.), and about 100 different strains (numbered
1,2,3, etc.) based on the genomic sequence heterogeneity.89
The variability is distributed throughout the genome. However, the non-
coding regions at either end of the genome (5'-UTR and 3'-UTR; UTR-
untranslated region) are more conserved and suitable for virus detection by
PCR.89
The genes coding for the envelope E1 and E2 glycoproteins are the most
variable. Amino acid changes may alter the antigenic properties of the
proteins, thus allowing the virus to escape neutralizing antibodies.89
Genotypes 1-3 have a worldwide distribution. Types 1a and 1b are the most
common, accounting for about 60% of global infections. They predominate in
Northern Europe and North America, and in Southern and Eastern Europe
and Japan, respectively. Type 2 is less frequently represented than type 1.
Type 3 isendemic in south-east Asia and is variably distributed in different
countries. Genotype 4 is principally found in the Middle East, Egypt, and
central Africa. Type 5 is almost exclusively found in South Africa, and
genotypes 6-11 are distributed in Asia.39, 58, 94, 103

21. PEGylation is the process of covalent attachment of polyethylene
glycol (PEG) polymer chains to another molecule, normally a drug or
therapeutic protein.. The covalent attachment of PEG to a drug or
therapeutic protein can "mask" the agent from the host's immune
system (reduced immunogenicity and antigenicity), and increase the
hydrodynamic size (size in solution) of the agent which prolongs its
circulatory time by reducing renal clearance. PEGylation can also
provide water solubility to hydrophobic drugs and proteins.

22. Contraindications to Treatment with
Side Effects of Treatmetn with
Interferon Alfa and Ribavirin
Iterferon Alfa and Ribavirin

23. Kidney Disease: Improving Global Outcomes
www.kdigo.org

24. Kidney Disease: Improving Global Outcomes
www.kdigo.org

25. Pegasys 135,180 mcg
Peg IF alpha 2a
(Roche)
PegIntron 50 mcg/0.5ml
(REDIPEN) 80,120,150
Peg IF alpha 2b
(Merck)
Copegus 200mg tab
(Roche)
Kidney Disease: Improving Global Outcomes
www.kdigo.org

26. Clinical Practice Guidelines for
the Diagnosis, Prevention and
Management of Hepatitis C in
CKD
(5)

27. Management

29. (Int J Artif organs)
March 2007
Kidney Disease: Improving Global Outcomes
www.kdigo.org

30. Kidney Disease: Improving Global Outcomes
www.kdigo.org

31. Kidney Disease: Improving Global Outcomes
www.kdigo.org

33. (6)

34. Rituximab, the monoclonal anti-CD20 antibody that
selectively targets the B cells, seems to be as least as
efficient as cyclophosphamide. Because it is also better
tolerated, it should be preferred to cyclophosphamide.
(7)

37. Cases

38. 1- 45 years old patient presented to renal
clinic worried about what he read on the
internet about effect of HCV on his kidney,,,
He has normal renal functions, normal urine
analysis, Not diabetic or hypertensive.
USS reveals normal kidney,,,
What would you do for this patient?
And what’s your evidence?
Kidney Disease: Improving Global Outcomes
www.kdigo.org

39. • Nothing
• At least annual FU.
Kidney Disease: Improving Global Outcomes
www.kdigo.org

40. 2- 40 y old HCV +ve patient presented with
mild LL edema, renal functions are normal,
urinary protein/cr ratio 2gm/day, Rh factor
negative, Cryo negative.
What would you do for this patient?
And what’s your evidence?
Kidney Disease: Improving Global Outcomes
www.kdigo.org

41. • Biopsy
• Antiproteinuric
• Antiviral treatment
Kidney Disease: Improving Global Outcomes
www.kdigo.org

42. • 43 y old male patient presented with HTN,
rash on LL, edema +++, oliguria
• Ix: Cr was 5 (with previous history Cr 1
since 2 month done on routine check)
• Urine revealed hematuria, proteinuria
(active sediment)
What would you do for this patient?
And what’sGlobal Outcomes
Kidney Disease: Improving
your evidence?
www.kdigo.org

43. • Pulse steroids
• Cyclophosphamide or Rituximab
• Plasma exchange
Kidney Disease: Improving Global Outcomes
www.kdigo.org

44. • 42 years old female patient presented with
2+ LL edema , renal impairment Cr 2.5,
• Urinary proteins 4 gm/day. She had HCV
diagnosed 2 years ago
What would you do for this patient?
And what’s your evidence?
Kidney Disease: Improving Global Outcomes
www.kdigo.org

45. • Area of debate.
• Antiviral for sure with dose modification.
• ??? Immunosuppression or not
• May be :
Antiviral ……. And if non responder :
Rituximab ???!!!
Kidney Disease: Improving Global Outcomes
www.kdigo.org

46. • Thank you
Kidney Disease: Improving Global Outcomes
www.kdigo.org