Progress in the treatment of proliferative lupus nephritis

Lupus nephritis is often well developed at the time of diagnosis. High-dose corticosteroids are universally accepted as the initial approach to the co ntrol of severe inflammation in the kidney. Long-term disease control and t he minimization of iatrogenic risk usually require adjunctive therapies tha t target the more fundamental immunoregulatory disturbances of lymphoid cel ls. Of the available cytotoxic drugs, cyclophosphamide is currently among t he most effective, although it cannot be considered ideal in terms of effic acy or toxicity. New prospects for the treatment of proliferative lupus nep hritis include novel immunosuppressive agents (e,g, mycophenolate, cyclospo rine, fludarabine), combination chemotherapy (e.g. cyclophosphamide plus fl udarabine), and sequential chemotherapy (e.g, cyclophosphamide-azathioprine ), immunological reconstitution using intensive cytoreductive chemotherapy (with or without stem cell rescue), co-stimulatory molecule inhibition (e.g . humanized anti-CD154 monoclonal antibody, CTLA4-Ig). Gene therapy remains an attractive prospect, but its feasibility clearly depends on the further definition of lupus-promoting genes and the availability of methods to est ablish stable expression of disease-corrective genes in the appropriate lym phoid cells. Curr Opin Nephrol Hypertens 9:107-115. (C) 2000 Lippincott Wil liams & Wilkins.