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Treatment of MPGN , What is the evidence?

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Evidence based treatment of MPGN based on latest KDIGO guidelines

Evidence based treatment of MPGN based on latest KDIGO guidelines

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  • 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)
  • 3. 1ry MPGN
  • 4. KDIGO www.kdigo.org
  • 5. Kidney Disease: Improving Global Outcomes (2) www.kdigo.org
  • 6. Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 7. Comprehensive clinical nephrology, 2010, P. 267-268 In Adults Asymptomatic Nephrotic syndrome RPGN with Non Nephrotic Or Impaired renal diffuse crescentsrange proteinuria functions Normal renal functions Pulse steroids and 6m CST Cyclophosphamides (Prednisone 1mg/kg BW/day) +/- plasmapheresisNo 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)
  • 8. 1ry MPGN• In children
  • 9. 2ry MPGN• Treatment of the cause.• We will concentrate on HBV, HCV associated MPGN.
  • 10. HBV Associated MPGN Comprehensive clinical nephrology, 2010, P. 268Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 11. 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. (4)
  • 15. HCV Associated MPGNand Cryoglobulinemia
  • 16. Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 17. Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 18. HCV genotypesHCV is classified into eleven major genotypes (designated 1-11), manysubtypes (designated a, b, c, etc.), and about 100 different strains (numbered1,2,3, etc.) based on the genomic sequence heterogeneity.89The 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 byPCR.89The genes coding for the envelope E1 and E2 glycoproteins are the mostvariable. Amino acid changes may alter the antigenic properties of theproteins, thus allowing the virus to escape neutralizing antibodies.89Genotypes 1-3 have a worldwide distribution. Types 1a and 1b are the mostcommon, accounting for about 60% of global infections. They predominate inNorthern Europe and North America, and in Southern and Eastern Europeand Japan, respectively. Type 2 is less frequently represented than type 1.Type 3 isendemic in south-east Asia and is variably distributed in differentcountries. Genotype 4 is principally found in the Middle East, Egypt, andcentral Africa. Type 5 is almost exclusively found in South Africa, andgenotypes 6-11 are distributed in Asia.39, 58, 94, 103
  • 19. PEGylation is the process of covalent attachment of polyethyleneglycol (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 hosts immunesystem (reduced immunogenicity and antigenicity), and increase thehydrodynamic 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.
  • 20. Contraindications to Treatment with Side Effects of Treatmetn with Interferon Alfa and Ribavirin Iterferon Alfa and Ribavirin
  • 21. Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 22. Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 23. 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
  • 24. Clinical Practice Guidelines forthe Diagnosis, Prevention and Management of Hepatitis C in CKD (5)
  • 25. Management
  • 26. (Int J Artif organs) March 2007Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 27. Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 28. Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 29. (6)
  • 30. Rituximab, the monoclonal anti-CD20 antibody that selectively targets the B cells, seems to be as least asefficient as cyclophosphamide. Because it is also bettertolerated, it should be preferred to cyclophosphamide. (7)
  • 31. Cases
  • 32. 1- 45 years old patient presented to renalclinic worried about what he read on theinternet about effect of HCV on his kidney,,,He has normal renal functions, normal urineanalysis, 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
  • 33. • Nothing• At least annual FU. Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 34. 2- 40 y old HCV +ve patient presented withmild LL edema, renal functions are normal,urinary protein/cr ratio 2gm/day, Rh factornegative, Cryo negative. What would you do for this patient? And what’s your evidence? Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 35. • Biopsy• Antiproteinuric• Antiviral treatment Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 36. • 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
  • 37. • Pulse steroids• Cyclophosphamide or Rituximab• Plasma exchange Kidney Disease: Improving Global Outcomes www.kdigo.org
  • 38. • 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
  • 39. • 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
  • 40. • Thank youKidney Disease: Improving Global Outcomes www.kdigo.org