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Cyclosporine (CsA) in lupus nephritis: assessing the evidence

2008; Oxford University Press; Volume: 24; Issue: 1 Linguagem: Inglês

10.1093/ndt/gfn565

1460-2385

Gabriella Moroni, Andrea Doria, Claudio Ponticelli,

Renal Transplantation Outcomes and Treatments

After more than 40 years since the first demonstration that high-dose corticosteroids can modify the relentless outcome of lupus nephritis [1], the ideal treatment of lupus nephritis is still far from being established. There is some agreement that the initial treatment should be aggressive, particularly in proliferative forms (so-called induction therapy) and should be followed by a maintenance regimen aimed at preventing flares of activity while minimizing the side effects of treatment. However, there are differing views on how to use the available immunomodulating drugs in the various phases of the disease. In particular, there is still much controversy about the current therapies for maintenance [2]. Notwithstanding the different approaches used, it should be noted that the treatment of systemic lupus erythematosus (SLE) nephritis relies on three main categories of drugs, i.e. corticosteroids, alkylating agents and inhibitors of purine synthesis. However, all these drugs have a narrow therapeutic index, and their prolonged administration can cause severe iatrogenic toxicity. In this review, we will try to assess whether cyclosporine (CsA), a drug that interferes with the immune response at levels different from those of corticosteroids and immunosuppressive drugs, may have a role to play in the therapeutic armamentarium of lupus nephritis. CsA is a pro-drug that gains pharmacological activity after binding to its specific cytoplasmic receptor cyclophylin. The complex CsA–cyclophylin interferes with a complex of phosphatases called calcineurin that has a key role in the immune response. Contact with the antigen-presenting cell generates a strong influx of calcium ions into the lympho-