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.

Key Words

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

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1 systemic lupus activity measure

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