Rheumatology International

, Volume 26, Issue 12, pp 1078–1083

Mycophenolate mofetil is effective in reducing lupus glomerulonephritis proteinuria

  • Eduardo F. Borba
  • Lissiane K. Guedes
  • Romy B. Christmann
  • Camille P. Figueiredo
  • Célio R. Gonçalves
  • Eloisa Bonfá
Original Article

Abstract

Mycophenolate mofetil (MMF) significantly reduces proteinuria in experimental model of human membranous nephropathy (Heymann nephritis). Twenty consecutive SLE patients with persistent isolated severe proteinuria and/or proteinuric flare were studied for 18 months of MMF therapy. All of them presented stable renal function and 12 had biopsy proven membranous glomerulonephritis (WHO class V). The starting daily dose for MMF was 1.5 g to a maximum of 3 g. Patients were divided into: partial response, ≥50% decrease of baseline proteinuria; complete response, normal proteinuria levels (less than 0.3 g/24 h); flare, increase of at least 50% of the mean baseline proteinuria. All 20 SLE patients (100%) presented a 50% reduction of baseline proteinuria which was achieved in 8.2±3.3 months of MMF therapy, at a mean daily dose of 2.3±0.5 g. A significant decrease in 24-h protein excretion was observed compared to entry (3.47±1.26 vs. 1.33±0.67 g, P<0.0001) as well as a correspondent increase of serum albumin (3.2±0.4 vs. 3.7±0.4 mg/dl, P=0.02) and reduction of prednisone dose (33.7±20.0 to 18.6±14.1 mg/day, P=0.01). Complete response was observed in 11 SLE patients (55%) in 12.2±3.0 months of therapy with a significant decrease in proteinuria (P<0.0001), prednisone dose (P<0.0001) and an increase of serum albumin (P=0.003). Interestingly, initial proteinuria or serum albumin levels did not identify patients with complete response and those with partial response at the end of the study (P=0.543 and 0.657, respectively). Our pilot prospective study suggests that MMF appears to be effective in reducing severe persistent proteinuria in lupus glomerulonephritis, even in patients unresponsive to other immunosuppressive treatments.

Keywords

Systemic lupus erythematosus Mycophenolate mofetil Proteinuria Membranous glomerulonephritis 

References

  1. 1.
    Fulton B, Markham A (1996) Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs 51:278–298PubMedCrossRefGoogle Scholar
  2. 2.
    Allison AC, Eugui EM (2000) Mycophenolate mofetil and its mechanisms of action. Immunopharmacology 47:85–118PubMedCrossRefGoogle Scholar
  3. 3.
    Jayne D (1999) Non-transplant uses for mycophenolate mofetil. Curr Opin Nephrol Hypertens 8:563–567PubMedCrossRefGoogle Scholar
  4. 4.
    Sollinger HW (1995) Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. US Renal Transplant Mycophenolate Mofetil Study Group. Transplantation 60:225–232PubMedCrossRefGoogle Scholar
  5. 5.
    European Mycophenolate Mofetil Cooperative Study Group (1995) Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. Lancet 345:1321–1325Google Scholar
  6. 6.
    Mathew TH for the Tricontinental Mycophenolate Mofetil Renal Transplatation Study Group (1998) A blinded, long-term, randomized multicenter study of mycophenolate mofetil in cadaveric renal transplantation. Results of three years. Transplantation 65:1450–1454CrossRefGoogle Scholar
  7. 7.
    Gaubitz M, Schorat A, Schotte H, Kern P, Domschke W (1999) Mycophenolate mofetil for the treatment of systemic lupus erythematosus: an open pilot trial. Lupus 8:731–736PubMedCrossRefGoogle Scholar
  8. 8.
    Kingdon EJ, McLean AG, Psimenou E et al (2001) The safety and efficacy of MMF in lupus nephritis: a pilot study. Lupus 10:606–611PubMedCrossRefGoogle Scholar
  9. 9.
    Karin MY, Alba P, Cuadrado MJ, Abbs IC, D’Cruz DP, Khamashta MA, Hughes GRV (2002) Mycophenolate mofetil for systemic lupus erythematosus refractory to other immunosuppressive agents. Rheumatology 41:876–882CrossRefGoogle Scholar
  10. 10.
    Briggs WA, Choi MJ, Scheel PJ Jr (1998) Successful mycophenolate mofetil treatment of glomerular disease. Am J Kidney Dis 31:213–217PubMedCrossRefGoogle Scholar
  11. 11.
    Glicklich D, Acharya A (1998) Mycophenolate mofetil therapy for lupus nephritis refractory to intravenous cyclophosphamide. Am J Kidney Dis 32:318–322PubMedCrossRefGoogle Scholar
  12. 12.
    Dooley MA, Cosio FG, Nachman PH et al (1999) Mycophenolate mofetil therapy in lupus nephritis: clinical observations. J Am Soc Nephrol 10:833–839PubMedGoogle Scholar
  13. 13.
    Contreras G, Pardo V, Leclercq B, Lenz O, Tozman E, O’Nan P, Roth D (2004) Sequential therapies for proliferative lupus nephritis. N Engl J Med 350:971–980PubMedCrossRefGoogle Scholar
  14. 14.
    Ding L, Zhao M, Zou W, Liu Y, Wang H (2004) Mycophenolate mofetil combined with prednisone for diffuse proliferative lupus nephritis: a histopathological study. Lupus 13(2):113–118PubMedCrossRefGoogle Scholar
  15. 15.
    Chan TM, Li FK, Tang CS et al (2000) Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis. Hong Kong–Guangzhou Nephrology Study Group. N Engl J Med 34:1156–1162CrossRefGoogle Scholar
  16. 16.
    Ginzler EM, Aranow C, Buyon J, Dooley MA, Merril JT, Petri M, Appel G, Gilkeson G, Wallace D, Weisman M (2003) A multicenter study of mycophenolate mofetil (MMF) vs. intravenous cyclophosphamide (FYC) as induction therapy for severe lupus nephritis (LN) Preliminary results. Arthritis Rheum 48(9):S647Google Scholar
  17. 17.
    Goyal S, Nousari HC (2001) Treatment of resistant discoid lupus erythematosus of the palms and soles with mycophenolate mofetil. J Am Acad Dermatol 45(1):142–144PubMedCrossRefGoogle Scholar
  18. 18.
    Hanjani NM, Nousari CH (2002) Mycophenolate mofetil for the treatment of cutaneous lupus erythematosus with smoldering systemic involvement. Arch Dermatol 138(12):1616–1618PubMedCrossRefGoogle Scholar
  19. 19.
    Schanz S, Ulmer A, Rassner G, Fierlbeck G (2002) Successful treatment of subacute cutaneous lupus erythematosus with mycophenolate mofetil. Br J Dermatol 147(1):174–178PubMedCrossRefGoogle Scholar
  20. 20.
    Vasoo S, Thumboo J, Fong KY (2003) Refractory immune thrombocytopenia in systemic lupus erythematosus: response to mycophenolate mofetil. Lupus 12(8):630–632PubMedCrossRefGoogle Scholar
  21. 21.
    Alba P, Karim MY, Hunt BJ (2003) Mycophenolate mofetil as a treatment for autoimmune haemolytic anaemia in patients with systemic lupus erythematosus and antiphospholipid syndrome. Lupus 12(8):633–635PubMedCrossRefGoogle Scholar
  22. 22.
    Riskalla MM, Somers EC, Fatica RA, McCune WJ (2003) Tolerability of mycophenolate mofetil in patients with systemic lupus erythematosus. J Rheumatol 30(7):1508–1512PubMedGoogle Scholar
  23. 23.
    Bijl M, Horst G, Bootsma H, Limburg PC, Kallenberg CG (2003) Mycophenolate mofetil prevents a clinical relapse in patients with systemic lupus erythematosus at risk. Ann Rheum Dis 62(6):534–539PubMedCrossRefGoogle Scholar
  24. 24.
    Ginzler EM, Aranow C, Merril JT, Orloff K, Henry D (2003) Toxicity and tolerability of mycophenolate mofetil (MMF) vs. intravenous cyclophosphamide (IVC) in a multicenter trial as induction therapy for lupus nephritis. Arthritis Rheum 48(9):S586–S587Google Scholar
  25. 25.
    Kolasinski SL, Chung JB, Albert DA (2002) What do we know about lupus membranous nephropathy? An analytic review. Arthritis Rheum 47(4):450–455PubMedCrossRefGoogle Scholar
  26. 26.
    Balow JE, Austin HA III (2003) Therapy of membranous nephropathy in systemic lupus erythematosus. Semin Nephrol 23(4):386–391PubMedCrossRefGoogle Scholar
  27. 27.
    Austin HA, Illei GG (2005) Membranous lupus nephritis. Lupus 14(1):65–71PubMedCrossRefGoogle Scholar
  28. 28.
    Penny MJ, Boyd RA, Hall M (1998) Mycophenolate mofetil prevents the induction of active Heymann nephritis: association with Th2 cytokine inhibition. J Am Soc Nephrol 9:2272–2282PubMedGoogle Scholar
  29. 29.
    Blume C, Heise G, Hess A, Waldner C, Grabensee B, Schroer K, Heering P (2005) Different effect of cyclosporine A and mycophenolate mofetil on passive Heymann nephritis in the rat. Nephron Exp Nephrol 100(2):104–112CrossRefGoogle Scholar
  30. 30.
    Zhao M, Chen X, Chen Y, Liu Z, Liu Y, Lu F, Zhang Y, Wang H (2003) Clinical observations of mycophenolate mofetil therapy in refractory primary nephrotic syndrome. Nephrology 8:105–109PubMedCrossRefGoogle Scholar
  31. 31.
    Miller G, Zimmerman R III, Radhakrishnan J, Appel G (2000) Use of mycophenolate mofetil in resistant membranous nephropathy. Am J Kidney Dis 36(2):250–256PubMedCrossRefGoogle Scholar
  32. 32.
    Kapitsinou PP, Boletis JN, Skopouli FN, Boki KA, Moutsopoulos HM (2004) Lupus nephritis: treatment with mycophenolate mofetil. Rheumatology 43:377–380PubMedCrossRefGoogle Scholar
  33. 33.
    Spetie DN, Tang Y, Rovin BH, Nadasdy T, Nadasdy G, Pesavento TE, Hebert LA (2004) Mycophenolate therapy of SLE membranous nephropathy. Kidney Int 66:2411–2415PubMedCrossRefGoogle Scholar
  34. 34.
    Pasquali S, Banfi G, Zucchelli A, Moroni G, Ponticelli C, Zucchelli P (1993) Lupus membranous nephropathy: long-term outcome. Clin Nephrol 39(4):175–182PubMedGoogle Scholar
  35. 35.
    Sloan RP, Schwartz MM, Korbet SM, Borok RZ (1996) Long-term outcome in systemic lupus erythematosus membranous glomerulonephritis. Lupus Nephritis Collaborative Study Group. J Am Soc Nephrol 7(2):299–305PubMedGoogle Scholar
  36. 36.
    Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277PubMedCrossRefGoogle Scholar
  37. 37.
    Churg J, Sobin LH (1982) Renal disease: classification and atlas of glomerular disease. Igaku-Shoin, TokyoGoogle Scholar
  38. 38.
    Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH (1992) Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 35:630–640PubMedCrossRefGoogle Scholar
  39. 39.
    Buratti S, Szer IS, Spencer CH, Bartosh S, Reiff A (2001) Mycophenolate mofetil treatment of severe renal disease in pediatric onset systemic lupus erythematosus. J Rheumatol 28(9):2103–2108PubMedGoogle Scholar
  40. 40.
    Wilmer WA, Rovin BH, Hebert CJ et al (2003) Management of glomerular proteinuria: a commentary. J Am Soc Nephrol 14:3217–3232PubMedCrossRefGoogle Scholar
  41. 41.
    Praga M, Gutierrez E, Gonzales E et al (2003) Treatment of IgA nephropathy with ACE inhibitors: a randomized and controlled trial. J Am Soc Nephrol 14:1578–1583PubMedCrossRefGoogle Scholar
  42. 42.
    Radhakrishnan J, Kunis CL, D’Agati V, Appel GB (1994) Cyclosporine treatment of lupus membranous nephropathy. Clin Nephrol 42:147–154PubMedGoogle Scholar
  43. 43.
    Hallegua D, Wallace DJ, Metzger AL, Rinaldi RZ, Klinenberg JR (2000) Cyclosporine for lupus membranous nephritis: experience with ten patients and review of the literature. Lupus 9:241–251PubMedCrossRefGoogle Scholar
  44. 44.
    Chan TM, Li FK, Hao WK et al (1999) Treatment of membranous lupus nephritis with nephrotic syndrome by sequential immunosupression. Lupus 8:545–551PubMedCrossRefGoogle Scholar
  45. 45.
    Moroni G, Macario M, Banfi G, Quaglini S, Ponticelli C (1998) Treatment of membranous lupus nephritis. Am J Kidney Dis 31:681–686PubMedCrossRefGoogle Scholar
  46. 46.
    Ginzler EM, Aranow C (2005) Mycophenolate mofetil in lupus nephritis. Lupus 14(1):59–64PubMedCrossRefGoogle Scholar
  47. 47.
    Reichert LJ, Koene RA, Wetzels JF (1998) Prognostic factors in idiopathic membranous nephropathy. Am J Kidney Dis 31:1–11PubMedCrossRefGoogle Scholar
  48. 48.
    Denton MD, Galvanek EG, Singh A, Sayegh MH (2001) Membranous lupus nephritis in a renal allograft: response to mycophenolate mofetil therapy. Am J Transplant 1(3):288–292PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Eduardo F. Borba
    • 1
  • Lissiane K. Guedes
    • 1
  • Romy B. Christmann
    • 1
  • Camille P. Figueiredo
    • 1
  • Célio R. Gonçalves
    • 1
  • Eloisa Bonfá
    • 1
  1. 1.Rheumatology Division, Faculdade de Medicina USPUniversity of São PauloSão PauloBrazil

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