Este documento presenta una revisión sobre la nefropatía lúpica. Incluye secciones sobre la epidemiología, biopsia renal, tratamiento de inducción y mantenimiento, rebiopsia, tratamiento de la nefropatía terminal y perspectivas futuras. El autor es un experto en enfermedades autoinmunes del Hospital Clínic de Barcelona.

2. NEFROPATÍA LÚPICA Dr. Ricard Cervera Servicio de Enfermedades Autoinmunes Hospital Clínic Barcelona

16. OBJETIVOS TERAPÉUTICOS 1975 Supervivencia en la fase aguda 19 90 Supervivencia a largo plazo con escasos efectos secundarios

18. Tratamiento secuencial 1. Pauta corta de CFM e.v. como tratamiento de inducción a la remisión (6 pulsos quincenales de 500 mg) 2. AZA como tratamiento de mantenimiento de la remisión « Euro-Lupus » Nephritis Trial

19. « Euro-Lupus » Nephritis Trial

20. « Euro-Lupus » Nephritis Trial

21. « Euro-Lupus » Nephritis Trial

22. « Euro-Lupus » Nephritis Trial

23. Micofenolato de Mofetilo

24. Micofenolato de Mofetilo

27. Comparison of the effects of MMF and of CYC in the induction of remission of severe LN 0.01 0.1 1 10 100 Complete remission Ginzler et al. (2005) Ong et al. (2005) Chan et al. (2005) Subtotal Partial remission Ginzler et al. (2005) Ong et al. (2005) Chan et al. (2005) Subtotal Overall remission Ginzler et al. (2005) Ong et al. (2005) Chan et al. (2005) Subtotal 3.89 (1.37, 11.05) 2.19 (0.06, 8.06) 0.98 (0.73, 1.32) 1.81 (0.70, 4.68) 1.20 (0.69, 2.07) 0.79 (0.35, 1.79) 1.07 (0.44, 2.61) 1.06 (0.71, 1.59) 1.71 (1.12, 2.61) 1.11 (0.65, 1.91) 1.00 (0.92, 1.09) 1.20 (0.85, 1.69) 16/71 5/19 24/33 45/123 21/71 6/19 8/33 35/123 37/71 11/19 32/33 80/123 4/69 3/25 23/31 30/125 17/69 10/25 7/31 34/125 21/69 13/25 30/31 64/125 30.0 25.0 45.0 100.0 54.7 24.5 20.8 100.0 28.7 22.6 48.7 100.0 Risk ratio (95% Cl) No. of events Control Treatment Weight % Risk ratio Favours CYC Favours MMF

28. 0 20 16 12 8 4 44 32 Azatioprina 135 Semanas Biopsia renal Metilprednisolona ev 750 mg x 3 Ciclofosfamida 500 mg cada 2 semanas MMF MMF ALMS

29. Micofenolato de Mofetilo Ensayo ALMS Appel GB et al. J Am Soc Nephrol 2009;20:1103–1112 Patients responding to treatment (%) Response rates of study population and by racial group 0 10 20 30 40 50 60 70 80 Overall Asia Caucasian Other Mycophenolate mofetil Intravenous cyclophosphamide

33. Gammaglobulinas e.v.

35. « Euro-Lupus» Nephritis Trial

37. 7 5 3 0 Proteinuria (g/24h) Duration of follow-up 6 4 1 MMF 3.0 2.0 1.0 0.0 Creatanine (mg/dl) Cr (CTX-AZA) Duration of follow-up 2.5 1.5 0.5 CrCl (CTX-AZA) Cr (MMF) CrCl (MMF) 120 100 80 60 40 20 0 Creatanine clearance (ml/mi) 2 CTX-AZA 0 1 2 3 4 5 6 7 0 1 2 3 4 5 6 7

40. Prognoses of patients receiving MMF and those receiving AZA in maintenance therapy of severe LN 0.01 0.1 1 10 100 Complete remission Contreras et al. (2004) Chan et al. (2005) Subtotal ESRD Contreras et al. (2004) Chan et al. (2005) Subtotal Relapse Contreras et al. (2004) Chan et al. (2005) Subtotal 2.86 (0.12, 66.11) 0.19 (0.01, 3.77) 0.70 (0.05, 10.09) 0.50 (0.15, 1.66) 1.17 (0.60, 2.29) 0.89 (0.41, 1.94) 0.95 (0.06, 14.13) 0.63 (0.11, 3.50) 0.71 (0.17, 3.01) 1/20 0/33 1/53 3/16 11/24 14/40 1/20 2/33 3/53 0/19 2/31 2/50 6/16 9/23 15/39 1/19 3/31 4/50 48.4 51.6 100.0 32.2 67.8 100.0 28.9 71.1 100.0 Risk ratio (95% Cl) No. of events Control Treatment Weight % Risk ratio Favours MMF Favours AZA Scr double Contreras et al. (2004) Chan et al. (2005) Subtotal 2.86 (0.12, 66.11) 0.19 (0.01, 3.77) 0.70 (0.05, 10.09) 1/20 0/33 1/53 0/19 2/31 2/50 48.4 51.6 100.0

42. 0 20 16 12 8 4 44 32 Azatioprina 135 Semanas Biopsia renal Metilprednisolona ev 750 mg x 3 Ciclofosfamida 500 mg cada 2 semanas MMF Ciclofosfamida 500 mg cada 2 semanas « Euro-Lupus » Maintain NephritisTrial

43. 19% 25% Ann Rheum Dis 2010; 69: 2083-9

45. ALMS trial

46. Ann Rheum Dis 2010; 69: 2059-61

55. END-STAGE LUPUS NEPHRITIS At some point, the risk of treatment-related morbidities may outweigh the likelihood of good treatment outcomes. Thus, physicians treating LN must know when to quit J H Stone. Lupus 1998;7:654

57. LES Y TRASPLANTE RENAL LES 54% Pérdidas injerto 38% Control e s Stone JH et al. Arthritis Rheum 1998;41:1438-45 .

59. Renal transplantation for systemic lupus erythematosus : excellent long-term results with both living and cadaveric donors Magee JC,et al. Transplantation Proc 1998;30:1798

60. Outcome of renal transplantation among patients with end-stage renal disease caused by lupus nephritis Period : 1987-1994 ( median follow up : 5 years ) End points : Graft failure and patient mortality Group A :772 adults with ESRD caused by SLE 32.644 adults with ESRD caused by other causes who received a cadaveric renal transplantation Group B : 390 adults with ESRD caused by SLE 10.512 adults with ESRD by other causes after first living- related transplantation CONCLUSION : Graft and patient survival after first cadaveric and first living -related renal transplants are similar in patients with ESRD caused by lupus nephritis and patients with ESRD from other causes. Ward M M. Kidney Inter 2000; 57: 2136

63. Houssiau, Arthritis Rheum 2009 N = 90 Mortality 7 (8%) End Stage Renal Disease 6 (5%) Creatinine 87 (1.0mg/dl) Cancer 7 (8%) Cardiac event 7 (8%) Ongoig therapy Immunosuppressive Prednisolone 56% 73%

64. Ac Mo anti-linf. T-B

65. Ac Mo anti-linf. B

66. Ac Mo anti-linf. B

67. P P Prof. David Isenberg

72. EXPLORER

73. LUNAR

74. Ac Mo anti-CD20 humanizado Ocrelizumab

77. STOP TRIAL 31-10-2009

78. Ac Mo frente a linf. B

79. Ac Mo anti-BLyS (Belimumab)

80. Ac Mo anti-TACI (Atacicept)

81. Ac Mo frente a linf. B

82. Ac Mo anti-CD22 (Epratuzumab)

83. Estudios Clínicos y Registros

84. Mensajes finales