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Mycophenolate Mofetil In Relapsing Lupus Nephritis
 

Mycophenolate Mofetil In Relapsing Lupus Nephritis

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MSN 2007 Abstract Presentation

MSN 2007 Abstract Presentation

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    Mycophenolate Mofetil In Relapsing Lupus Nephritis Mycophenolate Mofetil In Relapsing Lupus Nephritis Presentation Transcript

    • MYCOPHENOLATE MOFETIL IN RELAPSING LUPUS NEPHRITIS Chow YW, Yahya R, Visvanathan R Department of Nephrology, Kuala Lumpur Hospital
    • Introduction
      • Induction therapy
      • Intensive immunosuppressives
      • Objectives : to halt injury,
      • : recover renal function
      • : induce remission by controlling immunologic activity
      • Maintenance therapy
      • Longer period
      • Less intensive to reduce complication
      • Objectives : Consolidate remission
      • : Prevent flares
    • MYCOPHENOLATE MOFETIL IN LUPUS NEPHRITIS
      • Induction
        • Chan, NEJM 2000, 343 (16): 1156
        • Ginzler E, Appel G, NEJM 2005(353:21):2219
        • LM Ong, LS Hooi, Nephrology 2005(10) :504-510
      • Maintenance
        • Contreras, NEJM 2004, 350(10): 971
        • Chan et al, JASN 2005(16):1076-1084
    • Relapse Rate with current standard care Median: 38 months 39 38 Standard CYC & pulse MP Cortes-Hernandez 2003 Varied treatment Low dose steroid with Azathioprine Pulse CYC, pulse MP or combination Corticosteroid & immunosupressive Treatment Within 18 months 59 91 Mosca 2002 Mean : 40 months to first flare 37 46 El Hachmi 2003 CR: median 36 mths PR: median 18 mths 45 92 Illei 2002 Within 103 months 51 211 Beji 2005 Duration % n Publications
    • Objective
      • Significant proportion of patients with lupus nephritis
        • poor renal response to induction and maintenance pulse intravenous cyclophosphamide (CyP).
      • This study reports our experience with Mycophenolate Mofetil (MMF) in treatment of relapsing lupus nephritis.
    • Design & Methods
      • Six patients
      • Mean age of 25.67 + 5.18 years
      • WHO Class IV
        • 4 patients
      • WHO Class V
        • 2 patients
      • Relapsing lupus nephritis
        • Previously treated with
        • Intravenous CyP 0.75-1g/m2
        • (12-21 doses with cumulative dose of 13.23 + 2.4g)
        • Azathioprine (2.07 + 0.16 mg/kg body weight)
      • Treated with at least six months of MMF were included in the analysis
    • Design & Methods
      • 24 hour Urine Protein,
      • Serum Albumin,
      • Serum Creatinine,
      • Estimated GFR (eGFR)
      • Serum cholesterol
        • 1, 3 and 6 months
    • Definitions
      • Complete remission
      • Urinary protein excretion less than 0.3g/24hours and
      • Normal serum albumin (>30g/L) and
      • Improved or stable renal function
      • Partial remission
      • Urinary protein excretion reduced by > 50% with range of 0.3-3.0g/24hours and
      • Serum albumin > 30g/L
    • Definitions
      • Progressive renal impairment
      • Rise in serum creatinine > 50umol/l or
      • Decrease in creatinine clearance exceeding 15% of baseline
      • Treatment failure
      • Persistent urinary protein excretion > 3g/24hours or
          • Progressive renal impairment within 12 months of starting therapy
          • or
      • Permanent discontinuation of therapy as a result of drug side effects.
    • Result 30 2.0 IV M 27 Pt 6 10 2.0 IV F 30 Pt 5 27 2.0 IV F 28 Pt 4 6 2.0 IV F 17 Pt 3 18 1.0 V F 24 Pt 2 22 2.0 V F 28 Pt 1 F/up (mth) MMF dose WHO Class Sex Age
    • Result R 1.5 15.4 Skin, Jt Pt 6 R 1.5 14.6 Skin, Jt Pt 5 R 1.5 13.0 Skin, Jt Pt 4 R 2.0 13.4 Hemato, CNS Pt 3 R 2.4 12.0 CNS, Skin Pt 2 R 2.0 12.3 Hemato, Skin Pt 1 MMF Indi Aza (mg/kg) CYC (g) SLE Criteria
    • Result PR Losartan 100mg dly -- Pt 6 CR -- Perindopril 8mg dly Pt 5 PR -- Perindopril 8mg dly Pt 4 NR -- Enalapril 10mg BD Pt 3 NR* Telmisartan 80mg dly Perindopril 8mg dly Pt 2 CR Losartan 100mg dly Perindopril 8mg dly Pt 1 Response ARB ACEI
    • Result
      • Mean dose of MMF
        • 1.83 + 0.41 g/d
      • Mean duration of therapy
        • 14.17 + 7.39 months.
      • Mean time to response
        • 6.00 + 1.58 months
      • 24 hour urine protein
        • 1.62 + 0.89 to 0.86 + 1.22g/24 hours
      • Serum albumin
        • 23.00 + 5.13 to 31.17 + 10.89g/L
    • Result
        • Serum cholesterol
          • 7.87 + 3.61 to 5.65 + 2.00mmol/L
        • Renal function
          • 92.67 + 40.14 to 84.17 + 14.28umol/L
        • eGFR
          • 81.41 + 38.98 to 83.39 + 17.25mls/min/ 1.73m2
        • Serum complement component C3
          • 0.35 + 0.19 to 0.64 + 0.49g/L
    • Result: 24 hour urine protein 1.62 + 0.89 to 0.86 + 1.22g/24 hours
    • Result- Serum albumin 23.00 + 5.13 to 31.17 + 10.89g/L
    • Result- Serum cholesterol 7.87 + 3.61 to 5.65 + 2.00mmol/L
    • Result- Renal function 92.67 + 40.14 to 84.17 + 14.28umol/L
    • Results- eGFR 81.41 + 38.98 to 83.39 + 17.25mls/min/ 1.73m2
    • Results - C3 0.35 + 0.19 to 0.64 + 0.49g/L
    • Adverse Events
      • 2 patients had diarrhea
      • 1 patient had nausea during initial MMF therapy which disappeared with time.
    • Conclusion
      • MMF is an effective therapy for relapsing lupus nephritis and is well tolerated.
    • Discussion
    • MYCOPHENOLATE MOFETIL IN LUPUS NEPHRITIS
      • Induction
        • Chan, NEJM 2000, 343 (16): 1156
        • Ginzler E, Appel G, NEJM 2005(353:21):2219
        • LM Ong, LS Hooi, Nephrology 2005(10) :504-510
      • Maintenance
        • Contreras, NEJM 2004, 350(10): 971
        • Chan et al, JASN 2005(16):1076-1084
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    •  
    •