Lupus nephritis leads to significant morbidity and mortality in patients with systemic lupus erythematous. Immunosuppressive agents are recommended in management of Class III, IV and V lupus nephritis. The goals of therapy are to control the disease and to prevent relapse while minimizing side-effects of therapy. Most of the evidences in managements of Class III and IV lupus nephritis comes from randomized controlled trials using intravenous cyclophosphamides, oral mycophenolate mofetil and oral azathioprine. In Class V lupus nephritis, there are few studies available and they have assessed the use of intravenous cyclophsophamide, oral mycophenolates mofetil and oral cyclosporine. In this review article, we have summarized the major randomized controlled trials in managements of Class III, IV and V lupus nephritis and offer an interpretation of the evidence to date.
Weening, J.J., D’Agati, V.D., Schwartz, M.M., Seshan, S.V., Alpers, C.E., Appel, G.B., Balow, J.E., Bruijn, J.A., Cook, T., Ferrario, F., Fogo, A.B., Ginzler, E.M., Hebert, L., Hill, G., Hill, P., Jennette, J.C., Kong, N.C., Lesavre, P., Lockshin, M., Looi, L.M., Makino, H., Moura, L.A. and Nagata, M. (2004) The classification of glomerulonephritis in systemic lupus erythematosus revisited. Journal of the American Society of Nephrology, 15, 241-250. doi:10.1097/01.ASN.0000108969.21691.5D
Illei, G.G., Austin, H.A., Crane, M., Collins, L., Gourley, M.F., Yarboro, C.H., Vaughan, E.M., Kuroiwa, T., Danning, C.L., Steinberg, A.D., Klippel, J.H., Balow, J.E. and Boumpas, D.T. (2001) Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis. Annals of Internal Medicine, 135, 248-257.
Houssiau, F.A., Vasconcelos, C., D’Cruz, D., Sebastiani, G.D., Garrido Ed, E.R., Danieli, M.G., Abramovicz, D., Blockmans, D., Mathieu, A., Direskeneli, H., Galeazzi, M., et al. (2002) Immunosuppressive therapy in lupus nephritis: The Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis & Rheumatism, 46, 2121-2131. doi:10.1002/art.10461
Houssiau, F.A., Vasconcelos, C., D’Cruz, D., Sebastiani, G.D., de Ramon, G.E., Danieli, M.G., Abramovicz, D., Blockmans, D., Cauli, A., Direskeneli, H., Galeazzi, M., Gul, A., Levy, Y., Petera, P., Popovic, R., Petrovic, R., Sinico, R.A., Cattaneo, R., Font, J., Depresseux, G., Cosyns, J.P. and Cervera, R. (2010) The 10-year follow-up data of the Euro-Lupus Nephritis Trial comparing low-dose and high-dose intravenous cyclophosphamide. Annals of the Rheumatic Diseases, 69, 61-64. doi:10.1136/ard.2008.1025
Chan, T.M., Tse, K.C., Tang, C.S., Mok, M.Y. and Li, F.K. (2005) Long-term study of mycophenolate mofetil as continuous induction and maintenance treatment for diffuse proliferative lupus nephritis. Journal of the American Society of Nephrology , 16, 1076-1084. doi:10.1681/ASN.2004080686
Ong, L.M., Hooi, L.S., Lim, T.O., Goh, B.L., Ahmad, G., Ghazalli, R., Teo, S.M., Wong, H.S., Tan, S.Y., Shaariah, W., Tan, C.C. and Morad, Z. (2005) Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Nephrology, 10, 504-510. doi:10.1111/j.1440-1797.2005.00444.x
Ginzler, E.M., Dooley, M.A., Aranow, C., Kim, M.Y., Buyon, J., Merrill, J.T., Petri, M., Gilkeson, G.S., Wallace, D.J., Weisman, M.H. and Appel, G.B. (2005) Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis. The New England Journal of Medicine, 353, 2219-2228. doi:10.1056/NEJMoa043731
Appel, G.B., Contreras, G., Dooley, M.A., Ginzler, E.M., Isenberg, D., Jayne, D., Li, L.S., Mysler, E., Sanchez-Guerrero, J., Solomons, N. and Wofsy, D. (2009) Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. Journal of the American Society of Nephrology , 20, 1103-1112. doi:10.1681/ASN.2008101028
Contreras, G., Pardo, V., Leclercq, B., Lenz, O., Tozman, E., O’Nan, P. and Roth, D. (2004) Sequential therapies for proliferative lupus nephritis. The New England Journal of Medicine, 350, 971-980. doi:10.1056/NEJMoa031855
Miyasaka, N., Kawai, S. and Hashimoto, H. (2009) Efficacy and safety of tacrolimus for lupus nephritis: A placebo-controlled double-blind multicenter study. Modern Rheumatology, 19, 606-615. doi:10.1007/s10165-009-0218-5
Chen, W., Tang, X., Liu, Q., Chen, W., Fu, P., Liu, F., Liao, Y., Yang, Z., Zhang, J., Chen, J., Lou, T., Fu, J., Kong, Y., Liu, Z., Fan, A., Rao, S., Li, Z. and Yu, X. (2011) Short-term outcomes of induction therapy with tacrolimus versus cyclophosphamide for active lupus nephritis: A multicenter randomized clinical trial. American Journal of Kidney Diseases, 57, 235-244. doi:10.1053/j.ajkd.2010.08.036
Lewis, E.J., Hunsicker, L.G., Lan, S.P., Rohde, R.D. and Lachin, J.M. (1992) A controlled trial of plasmapheresis therapy in severe lupus nephritis. New England Journal of Medicine, 326, 1373-1379. doi:10.1056/NEJM199205213262101
Melander, C., Sallee, M., Trolliet, P., Candon, S., Belenfant, X., Daugas, E., Remy, P., Zarrouk, V., Pillebout, E., Jacquot, C., Boffa, J.J., Karras, A., Masse, V., Lesavre, P., Elie, C., Brocheriou, I., Knebelmann, B., Noel, L.H. and Fakhouri, F. (2009) Rituximab in severe lupus nephritis: Early B-cell depletion affects long-term renal outcome. Clinical Journal of the American Society of Nephrology, 4, 579-587. doi:10.2215/CJN.04030808
Bosch, X. (2010) Inflammation: Rituximab in ANCA vasculitis and lupus: Bittersweet results. Nature Reviews Nephrology, 6, 137-139. doi:10.1038/nrneph.2010.13
Jayne, D., Passweg, J., Marmont, A., Farge, D., Zhao, X., Arnold, R., Hiepe, F., Lisukov, I., Musso, M., Ou-Yang, J., Marsh, J., Wulffraat, N., Besalduch, J., Bingham, S.J., Emery, P., Brune, M., Fassas, A., Faulkner, L., Ferster, A., Fiehn, C., Fouillard, L., Geromin, A., Greinix, H., Rabusin, M., Saccardi, R., Schneider, P., Zintl, F., Gratwohl, A. and Tyndall, A. (2004) Autologous stem cell transplantation for systemic lupus erythematosus. Lupus, 13, 168-176. doi:10.1191/0961203304lu525oa
Burt, R.K., Traynor, A., Statkute, L., Barr, W.G., Rosa, R., Schroeder, J., Verda, L., Krosnjar, N., Quigley, K., Yaung, K., Villa, B.M., Takahashi, M., Jovanovic, B., Oyama, Y. (2006) Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus erythematosus. Journal of the American Medical Association, 295, 527-535. doi:10.1001/jama.295.5.527
Austin III, H.A., Illei, G.G., Braun, M.J., Balow, J.E. (2009) Randomized, controlled trial of prednisone, cyclophosphamide, and cyclosporine in lupus membranous nephropathy. Journal of the American Society of Nephrology, 20, 901-911. doi:10.1681/ASN.2008060665
Radhakrishnan, J., Moutzouris, D.A., Ginzler, E.M., Solomons, N., Siempos, I.I. and Appel, G.B. (2010) Mycophenolate mofetil and intravenous cyclophosphamide are similar as induction therapy for class V lupus nephritis. Kidney International, 77, 152-160. doi:10.1038/ki.2009.412
Clark, W.F. and Sontrop, J.M. (2008) What have we learned about optimal induction therapy for lupus nephritis (III through V) from randomized, controlled trials? Clinical Journal of the American Society of Nephrology, 3, 895-898. doi:10.2215/CJN.00170108