Calcineurin inhibitors in lupus nephritis

Abstract

Claudio Ponticelli: Retired from Ospedale Maggiore Milano. Maintenance immunosuppressive treatment of lupus nephritis is aimed at preventing flares and maintaining stable renal function. The combination of low-dose glucocorticoids and a purine synthesis inhibitor (azathioprine or mycophenolate) is currently considered as the standard of care. This therapeutic strategy improves clinical outcomes in patients with lupus nephritis, however it may not be sufficient to completely abrogate proteinuria in some cases. In addition, albeit displaying a favourable safety profile, such treatment may be burdened by gastrointestinal side-effects, hematologic toxicity and severe infections. Calcineurin inhibitors (CNI) also proved effective and well tolerated in the mid-term for lupus nephritis [1, 2]. In this issue, Argolini et al. compared the effects of cyclosporine (CsA), mycophenolate (MPA) and azathioprine (AZA) as maintenance treatment in 106 patients with lupus nephritis. The authors found no differences among treatments in maintaining stable kidney function and complete remission, although patients treated with CsA had significantly higher baseline proteinuria. After 8 years of follow-up, the authors observed a trend towards reduced frequency of renal flares in patients given CsA compared to those treated with MPA or AZA, even though the difference did not reach statistical significance. No difference in the number and severity of side effects was demonstrated among groups [3]. These data are intriguing and may spark renewed interest for the use of CNI in the long-term maintenance treatment of lupus nephritis, although concerns remain about their potential toxicity. A good knowledge of pharmacologic characteristics of CNI and their interactions with other drugs may considerably reduce the risk of side effects.

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