ࡱ;   Root Entry F{K8CompObjaWordDocumentFObjectPoolTK8TK8 4@   FDocumento Microsoft Word 6 MSWordDocWord.Document.6;  Oh+'0$ H l   D hP:\APLIPC\WINWORD\NORMAL.DOTEWPSLE Informtica Informtica@ܥe= eF ppppppp  1"sT0p pppppppp-EWPSLE EURO-LUPUS NEPHRITIS TRIAL INTRODUCTION The Euro-Lupus Nephritis Trial : a multicenter controlled trial comparing two intravenous cyclophosphamide regimens. About half of the patients with systemic lupus erythematosus (SLE) suffer from nephritis characterized by proteinuria, nephrotic syndrome and/or kidney failure (1). Although glucocorticoids still remain the cornerstone treatment for lupus nephritis, the long-term use of steroids is associated with severe side-effects that contribute to the so-called "late-onset" morbidity and mortality currently associated with lupus. In the last 15 years, several clinical trials concluded that addition of immunosuppressive drugs such as azathioprine or cyclophosphamide (CPM) had a steroid-sparing effect and reduced the risk of impaired renal function and end-stage renal disease (ESRD) in patients with lupus nephritis. A major step forward was gained from the National Institutes of Health prospective trials demonstrating that patients given steroid therapy combined with intermittent intravenous (IV) pulses of CPM had a lower risk of impaired renal function in the long-term compared to patients given steroid therapy alone (2-4). Therefore, combined therapy with glucocorticoids and intermittent IV pulses of CPM - usually prescribed for a 30 month-period - is the current standard treatment for lupus nephritis. However, this long course IV CPM regimen increases the risk of severe infections and of permanent gonadal failure, a dire consequence for young female patients. Among the alternative approaches, the clinical experience gained by some investigators suggests that a short course IV CPM - a few weeks or months instead of 30 months - followed by azathioprine, a much less toxic immunosuppressive drug, also preserves renal function of lupus nephritis patients and is associated with a low toxicity and no risk of premature menopause (5, 6). However, no controlled studies have been designed thus far to validate this approach. References 1. Cervera R, Khamashta MA, Font J, Sebastiani GD, Gil A, Lavilla P, Domnech I, Aydintug AO, Jedryka-Goral A, de Ramon E, Galeazzi M, Haga H-J, Mathieu A, Houssiau F, Inguelmo M, Hughes GRV, and the European Working Party on Systemic Lupus Erythematosus. Systemic lupus erythematosus: clinical and immunologic patterns of disease expression in a cohort of 1,000 patients. Medicine 72 : 113-124, 1993. 2. Austin HA, Klippel JH, Balow JE, le Riche NGH, Steinberg AD, Plotz PH, Decker JL. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med 314 : 614-619, 1986. 3. Steinberg AD, Steinberg SC. Long-term preservation of renal function in patients with lupus nephritis receiving treatment that includes cyclophosphamide versus those treated with prednisone only. Arthritis Rheum 34 : 945-950, 1991. 4. Boumpas DT, Austin HA, Vaughn EM, Klippel JH, Steinberg AD, Yarboro CH, Balow JE. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 340 : 741-745, 1992. 5. Houssiau FA, D'Cruz D, Haga H-J, Hughes GRV. Short course of weekly low-dose intravenous pulse cyclophosphamide in the treatment of lupus nephritis : a preliminary study. Lupus 1 : 31-35, 1991. 6. Cuadrado MJ, D'Cruz D, Lloyd ME, Mujic F, Taub N, Khamashta MA, Hughes GRV. Immunosuppressive therapy in lupus nephritis: five year follow-up. Arthritis Rheum 37 : S180, 1994. .Aࡱ; SummaryInformation(K8@@K8@F#Microsoft Word 6.01ࡱ; 2 u ^cIccI UcIUc#$12 } ~ H I 67 !8!h8!h8!h8!h8!h8!h8!h8!h8!h8!8!8!8!8!8!8!8!8!8!8!8!8!8!8!8!8!  0 _hK@Normala(A@(Fuente de prrafo predeter. !! h  - InformticaC:\WEBS\EWPSLE\TEXT\NEFINT.HTM@Epson Stylus COLOR IILPT1:EPST2Epson Stylus COLOR II @Dn- 4dhhA= Epson Stylus COLOR II @Dn- 4dhhA=  1Times New Roman Symbol &Arial"&&Y0EWPSLE Informtica Informticaࡱ;