Mycophenolate Mofetil In Relapsing Lupus Nephritis

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Mycophenolate Mofetil In Relapsing Lupus Nephritis

  1. 1. MYCOPHENOLATE MOFETIL IN RELAPSING LUPUS NEPHRITIS Chow YW, Yahya R, Visvanathan R Department of Nephrology, Kuala Lumpur Hospital
  2. 2. Introduction <ul><li>Induction therapy </li></ul><ul><li>Intensive immunosuppressives </li></ul><ul><li>Objectives : to halt injury, </li></ul><ul><li>: recover renal function </li></ul><ul><li>: induce remission by controlling immunologic activity </li></ul><ul><li>Maintenance therapy </li></ul><ul><li>Longer period </li></ul><ul><li>Less intensive to reduce complication </li></ul><ul><li>Objectives : Consolidate remission </li></ul><ul><li> : Prevent flares </li></ul>
  3. 3. MYCOPHENOLATE MOFETIL IN LUPUS NEPHRITIS <ul><li>Induction </li></ul><ul><ul><li>Chan, NEJM 2000, 343 (16): 1156 </li></ul></ul><ul><ul><li>Ginzler E, Appel G, NEJM 2005(353:21):2219 </li></ul></ul><ul><ul><li>LM Ong, LS Hooi, Nephrology 2005(10) :504-510 </li></ul></ul><ul><li>Maintenance </li></ul><ul><ul><li>Contreras, NEJM 2004, 350(10): 971 </li></ul></ul><ul><ul><li>Chan et al, JASN 2005(16):1076-1084 </li></ul></ul>
  4. 4. 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
  5. 5. Objective <ul><li>Significant proportion of patients with lupus nephritis </li></ul><ul><ul><li>poor renal response to induction and maintenance pulse intravenous cyclophosphamide (CyP). </li></ul></ul><ul><li>This study reports our experience with Mycophenolate Mofetil (MMF) in treatment of relapsing lupus nephritis. </li></ul>
  6. 6. Design & Methods <ul><li>Six patients </li></ul><ul><li>Mean age of 25.67 + 5.18 years </li></ul><ul><li>WHO Class IV </li></ul><ul><ul><li>4 patients </li></ul></ul><ul><li>WHO Class V </li></ul><ul><ul><li>2 patients </li></ul></ul><ul><li>Relapsing lupus nephritis </li></ul><ul><ul><li>Previously treated with </li></ul></ul><ul><ul><li>Intravenous CyP 0.75-1g/m2 </li></ul></ul><ul><ul><li>(12-21 doses with cumulative dose of 13.23 + 2.4g) </li></ul></ul><ul><ul><li>Azathioprine (2.07 + 0.16 mg/kg body weight) </li></ul></ul><ul><li>Treated with at least six months of MMF were included in the analysis </li></ul>
  7. 7. Design & Methods <ul><li>24 hour Urine Protein, </li></ul><ul><li>Serum Albumin, </li></ul><ul><li>Serum Creatinine, </li></ul><ul><li>Estimated GFR (eGFR) </li></ul><ul><li>Serum cholesterol </li></ul><ul><ul><li>1, 3 and 6 months </li></ul></ul>
  8. 8. Definitions <ul><li>Complete remission </li></ul><ul><li>Urinary protein excretion less than 0.3g/24hours and </li></ul><ul><li>Normal serum albumin (>30g/L) and </li></ul><ul><li>Improved or stable renal function </li></ul><ul><li>Partial remission </li></ul><ul><li>Urinary protein excretion reduced by > 50% with range of 0.3-3.0g/24hours and </li></ul><ul><li>Serum albumin > 30g/L </li></ul>
  9. 9. Definitions <ul><li>Progressive renal impairment </li></ul><ul><li>Rise in serum creatinine > 50umol/l or </li></ul><ul><li>Decrease in creatinine clearance exceeding 15% of baseline </li></ul><ul><li>Treatment failure </li></ul><ul><li>Persistent urinary protein excretion > 3g/24hours or </li></ul><ul><ul><ul><li>Progressive renal impairment within 12 months of starting therapy </li></ul></ul></ul><ul><ul><ul><li>or </li></ul></ul></ul><ul><li>Permanent discontinuation of therapy as a result of drug side effects. </li></ul>
  10. 10. 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
  11. 11. 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
  12. 12. 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
  13. 13. Result <ul><li>Mean dose of MMF </li></ul><ul><ul><li>1.83 + 0.41 g/d </li></ul></ul><ul><li>Mean duration of therapy </li></ul><ul><ul><li>14.17 + 7.39 months. </li></ul></ul><ul><li>Mean time to response </li></ul><ul><ul><li>6.00 + 1.58 months </li></ul></ul><ul><li>24 hour urine protein </li></ul><ul><ul><li>1.62 + 0.89 to 0.86 + 1.22g/24 hours </li></ul></ul><ul><li>Serum albumin </li></ul><ul><ul><li>23.00 + 5.13 to 31.17 + 10.89g/L </li></ul></ul>
  14. 14. Result <ul><ul><li>Serum cholesterol </li></ul></ul><ul><ul><ul><li>7.87 + 3.61 to 5.65 + 2.00mmol/L </li></ul></ul></ul><ul><ul><li>Renal function </li></ul></ul><ul><ul><ul><li>92.67 + 40.14 to 84.17 + 14.28umol/L </li></ul></ul></ul><ul><ul><li>eGFR </li></ul></ul><ul><ul><ul><li>81.41 + 38.98 to 83.39 + 17.25mls/min/ 1.73m2 </li></ul></ul></ul><ul><ul><li>Serum complement component C3 </li></ul></ul><ul><ul><ul><li>0.35 + 0.19 to 0.64 + 0.49g/L </li></ul></ul></ul>
  15. 15. Result: 24 hour urine protein 1.62 + 0.89 to 0.86 + 1.22g/24 hours
  16. 16. Result- Serum albumin 23.00 + 5.13 to 31.17 + 10.89g/L
  17. 17. Result- Serum cholesterol 7.87 + 3.61 to 5.65 + 2.00mmol/L
  18. 18. Result- Renal function 92.67 + 40.14 to 84.17 + 14.28umol/L
  19. 19. Results- eGFR 81.41 + 38.98 to 83.39 + 17.25mls/min/ 1.73m2
  20. 20. Results - C3 0.35 + 0.19 to 0.64 + 0.49g/L
  21. 21. Adverse Events <ul><li>2 patients had diarrhea </li></ul><ul><li>1 patient had nausea during initial MMF therapy which disappeared with time. </li></ul>
  22. 22. Conclusion <ul><li>MMF is an effective therapy for relapsing lupus nephritis and is well tolerated. </li></ul>
  23. 23. Discussion
  24. 24. MYCOPHENOLATE MOFETIL IN LUPUS NEPHRITIS <ul><li>Induction </li></ul><ul><ul><li>Chan, NEJM 2000, 343 (16): 1156 </li></ul></ul><ul><ul><li>Ginzler E, Appel G, NEJM 2005(353:21):2219 </li></ul></ul><ul><ul><li>LM Ong, LS Hooi, Nephrology 2005(10) :504-510 </li></ul></ul><ul><li>Maintenance </li></ul><ul><ul><li>Contreras, NEJM 2004, 350(10): 971 </li></ul></ul><ul><ul><li>Chan et al, JASN 2005(16):1076-1084 </li></ul></ul>

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