Lupusnephritis - Fortschritt durch neue immunsuppressive Therapiekonzepte?

Zusammenfassung

30-50 % aller Patienten, die an einem systemischen Lupus erythematodes leiden, entwickeln eine Glomerulonephritis. Die Therapie richtet sich nach dem vorliegenden Schweregrad der Erkrankung: So profitieren Patienten mit einer proliferativen Lupusnephritis am stärksten von einer immunsuppressiven Therapie. Bei leichter ausgeprägten Formen des systemischen Lupus erythematodes (WHO-Grad I und II) oder auch bei der membranösen Lupusnephritis (WHO-Grad V) ist der Wert solcher Therapiestrategien jedoch umstritten. Als Therapiestandard gilt momentan die Cyclophosphamid-Puls-Therapie mit einer geringeren Kumulativdosis. Da Cyclophosphamid jedoch erhebliche und schwer wirkende Nebenwirkungen auslösen kann (Sekundärinfektionen, Myelotoxizität, Gonadentoxizität), wird momentan nach neuen Therapieoptionen gesucht, mit denen die Cyclophosphamiddosis reduziert werden kann. Bereits nach sechs Monaten ist eine Umstellung der Behandlung auf eine Erhaltungstherapie - z.B. mit Azathioprin - möglich, wenn die Patienten auf die Therapie ansprechen (renale Remission). Besser zu eignen scheint sich Mykophenolatmofetil, insbesondere, da die Substanz auch im Vergleich zum Azathioprin eine relativ geringe Nebenwirkungsrate aufweist. Das einzige kurative Behandlungskonzept, die Stammzelltransplantation, ist leider mit einer hohen Mortalitätsrate behaftet. Daher sollte dieses Konzept jungen Patienten mit einem hoch aktiven Lupus erythematodes und einem Multiorganversagen vorbehalten bleiben.

Summary

30-50 % of all patients suffering from systemic lupus erythematosus (SLE) develop glomerulonephritis. Treatment is determined by the severity of the condition: patients with a proliferative systemic lupus erythematosus benefit most from immunosuppressive therapy. In the case of less severe forms of SLE (WHO grades I and II) or membranous lupus nephritis (WHO grade IV), however, the value of such therapeutic strategies is controversial. Currently, the standard treatment protocol is pulse cyclophosphamide at a low cumulative dose. Since, however, cyclophosphamide may trigger appreciable and even severe side effects (secondary infections, myelosuppression, loss of gonadal function), new treatments are currently being sought with the aim of reducing the cyclophosphamide dose. Already after six months, conversion to maintenance treatment - for example, with azathioprine - is possible in patients who respond to this treatment (renal remission). A more suitable option appears to be mycophenolate mofetil, in particular since the substance has a lower rate of side effects, also in comparison with azathioprine. The sole curative treatment concept, namely stem cell transplantation, is, unfortunately, associated with a high mortality rate, so that this concept should be restricted to young patients with highly active systemic lupus erythematosus and multiorgan failure.

systemic lupus erythematosus - glomerulonephritis - pulse cyclophosphamide treatment - stem cell transplantation - immunosuppresive agents

Literatur

• 1 Anolik JH, Campbell D, Felgar RE. et al. . The relationship of FCgammaRIIIa genotype to degree of B cell depletion by rituximab in the treatment of SLE.  Arthritis Rheum. 2003;  48 455-459
• 2 Austin HA, Klippel JH, Balow JE. et al. . Therapy of lupus nephritis: controlled trial of prednisone and cytotoxic drugs.  N Engl J Med. 1986;  314 614-619
• 3 Austin HA, Vaughan EM, Boumpas DT. et al. . Lupus membranous nephropathy: controlled trial of prednisone, pulse cyclophosphamide and cyclosporine [abstract].  J Am Soc Nephrol. 2000;  11
• 4 Bansal VK, Beto KA. Treatment of lupus nephritis: a meta analysis of clinical trials.  Am J Kid Dis. 1997;  21 239-250
• 5 Barlow JE, Austin HA 3rd. Progress in the treatment of proliferative lupus nephritis.  Curr Opin Nephrol Hypertens. 2000;  9 107-115
• 6 Boumpas DT, Austin HA, Vaughn EM. et al. . Controlled trial of methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis.  Lancet. 1992;  240 741-745
• 7 Braun N, Erley C, Klein R. et al. . Immunoadsorption onto protein A induces remission in severe systemic lupus erythematodes.  Nephrol Dial Transplant. 2000;  15 1367-1372
• 8 Danieli MG, Palmieri C, Salvi A. et al. . Synchronised therapy and high-dose cyclophosphamide in proliferative lupusnephritis.  J Clin Apheresis. 2002;  17 72-77
• 9 Donadio JV, Glassock RJ. Immunosuppressive therapy in lupus nephritis.  Am J Kid Dis. 1993;  21 239-250
• 10 Donadio JV, Hart GM, Bergstralh EJ, Holley KE. Prognostic determinants in lupus nephritis: a long-term clinico pathologic study.  Lupus. 1995;  4 109-115
• 11 Dooley MA, Cosio FG, Nachman PH. et al. . MMF therapy in lupus nephritis: clinical observations.  J Am Soc Nephrol. 1999;  10 833-839
• 12 Favre H, Miescher PA, Yuang YP. et al. . Cyclosporine in the treatment of lupusnephritis.  Am J Nephrol. 1989;  91 573-580
• 13 Hallegua D, Wallace DJ, Metzger AL. et al. . Cyclosporine for lupus membranous nephritis: experience with ten patients and review of the literature.  Lupus. 2000;  9 241-251
• 14 Haubitz M, Schellong S, Gobel U. et al. . Intravenous pulse administration of cyclophosphamide versus daily oral treatment in patients with antineutrophil cytoplasmic antibody-associated vasculitis and renal involvement: a prospective, randomized study.  Arthritis Rheum. 1998;  41 1835-1844
• 15 Hejaili FF, Louise MM, Clark WF. Treatment of lupus nephritis.  Drugs. 2003;  63 257-263
• 16 Hoisseau FA, Vasconcelos C, D'Cruz D. et al. . Immunosuppressive therapy in lupus nephritis: the Euro-Lupus-Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide.  Arthritis Rheum. 2002;  46 2121-2131
• 17 Hu W, Liu Z, Chen H. et al. . Mycophenolate mofetil vs. cyclophosphamide therapy for patients with diffuse proliferative lupus nephritis.  Chin Med J Engl. 2002;  115 705-709
• 18 Ioannidis JP, Boki KA, Katsorida ME. et al. . Remission, relaps and re-remission of proliferative lupus nephritis treated with cyclophosphamide.  Kidney Int. 1998;  57 258-264
• 19 Karim MY, Alba P, Coadrad MJ. et al. . MMF for SLE refractory to other immunosuppressive agents.  Rheumatology. 2002;  41 876-882
• 20 Kneitz C, Wilhelm M, Tony HP. Effective B cell depletion with rituximab in the treatment of autoimmune disease.  Immunobiology. 2002;  206 519-527
• 21 Leandro MJ, Edwards JC, Cambridge G. et al. . An open study of B lymphocyte depletion in systemic lupus erythematodes.  Arthritis Rheum. 2002;  46 2673-2677
• 22 Mac JR Gowan, Ellis S, Griffiths M, Isenberg DA. Retroperspective analysis of outcome in a cohort of patients with lupus nephritis treated between 1977 and 1999.  Rheumatology. 2002;  41 981-987
• 23 Mageed RA, Prud'homme GJ. Immunopathology and the gene therapy of lupus.  Gene Therapy. 2003;  10 861-874
• 24 Najafi CC, Korbet SM, Lewis EJ. et al. . Lupus prognosis in severe lupus glomerulonephritis: Significance of histological patterns of glomerular injury upon long-term prognosis in severe lupus glomerulonephritis.  Kidney Int. 2001;  59 2156-2163
• 25 Nikolov DG, Pandeva SM, Kumchev EP. et al. . Treatment for immunenephropathies with high doses of immunoglobulins.  Folia Med. 2003;  42 10-13
• 26 Nossent HC, Koldingsnes W. Long term efficacy of azathioprine treatment for proliferative lupus nephritis.  Rheumatology. 2000;  39 396-374
• 27 Schneider M, Gaubitz M, Perniok A. Immunadsorption in systemic connective tissue diseases and primary vasculitis.  Ther Apher. 1997;  1 117-120
• 28 Smith RE, Bryant J, DeCillis A, Andersson S. National surgical breast and bowel project experience.  J Clin Oncol. 2003;  21 1195-1204
• 29 Traynor AE, Barr WG, Rosa RM. et al. . Hematopoetic stem cell transplantation for severe and refractory lupus. Analysis after five years and fifteen patients.  Arthritis Rheum. 2002;  46 2917-2923
• 30 Tricontintal Mycophenolate mofetil Renal Transplantation Study Group . A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation.  Transplantation. 1996;  61 1029-1037

1 systemic lupus activity measure

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