Treatment of MPGN , What is the evidence?

TREATMENT OF MPGNWhat is the evidence?

byMohamed Essam

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)

1ry MPGN

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KDIGO

Kidney Disease: Improving Global Outcomes

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(2)


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In Adults

Asymptomatic Non

Nephrotic range

proteinuriaNormal renal

functionsNo specific treatment

Close FU / 3m

Nephrotic syndrome

Or Impaired renal functions

6m CST(Prednisone 1mg/kg BW/day)

+/- Cytotoxic drugs

Considerable reduction of proteinuria

Continue CST at the minimal effective dose

If no response within 3m

Stop CSTR with Cyclosp, Tac or

MMF(3)

RPGN with diffuse crescents

Pulse steroids and Cyclophosphamides+/- plasmapheresis

Comprehensive clinical nephrology, 2010, P. 267-268

1ry MPGN• In children

2ry MPGN

• Treatment of the cause.• We will concentrate on HBV, HCV associated

MPGN.


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HBV Associated MPGN

Comprehensive clinical nephrology, 2010, P. 268


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HCV Associated MPGN and Cryoglobulinemia


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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

http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index7.html#g

http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index7.html#g

http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index8.html#89

http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index7.html#v


http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index7.html#p

http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index7.html#a

http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index7.html#a


http://www.who.int/csr/disease/hepatitis/whocdscsrlyo2003/en/index7.html#e





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.

http://en.wikipedia.org/wiki/Polyethylene_glycol

http://en.wikipedia.org/wiki/Polyethylene_glycol

http://en.wikipedia.org/wiki/Immunogenicity

http://en.wikipedia.org/wiki/Antigenicity

http://en.wikipedia.org/wiki/Renal

http://en.wikipedia.org/wiki/Hydrophobic

Contraindications to Treatment with

Iterferon Alfa and Ribavirin

Side Effects of Treatmetn with Interferon Alfa and

Ribavirin


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Pegasys 135,180 mcgPeg IF alpha 2a

(Roche)

PegIntron 50 mcg/0.5ml(REDIPEN) 80,120,150

Peg IF alpha 2b(Merck)

Copegus 200mg tab(Roche)

Clinical Practice Guidelines for the Diagnosis, Prevention and Management of Hepatitis C in

CKD

(5)

Management


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(Int J Artif organs) March 2007


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Rituximab, the monoclonal anti-CD20 antibody thatselectively targets the B cells, seems to be as least as

efficient as cyclophosphamide. Because it is also bettertolerated, it should be preferred to cyclophosphamide.

(7)


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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?


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• Nothing• At least annual FU.


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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.




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• Biopsy• Antiproteinuric• Antiviral treatment


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• 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)




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• Pulse steroids• Cyclophosphamide or Rituximab• Plasma exchange


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• 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




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• Area of debate.• Antiviral for sure with dose modification.• ??? Immunosuppression or not • May be :

Antiviral ……. And if non responder :

Rituximab ???!!!


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• Thank you

Treatment of MPGN , What is the evidence?

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