Treatment options for proliferative lupus nephritis: an update of clinical trial evidence

Systemic lupus erythematosus involves the kidney in up to 60% of patients, and if untreated, may result in complete loss of kidney function. In this article, we review meta-analyses and clinical trial data on the therapeutic options for proliferative lupus nephritis, and complete a meta-analysis of the use of mycophenolate mofetil (MMF) compared with cyclophosphamide-based regimens. Clinical trials have found that cyclophosphamide-based regimens result in a decreased risk of end-stage renal disease, but are associated with significant toxicity in lupus nephritis. Even though the survival advantage of the US National Institutes of Health and Euro-Lupus regimens based on intravenous and oral cyclophosphamide has not been established, these approaches are broadly adopted in proliferative lupus nephritis. Recent studies have confirmed the therapeutic equivalence and potential comparative superiority of MMF and cyclophosphamide in induction of remission in patients with lupus nephritis. Use of MMF resulted in a lower incidence of infection and loss of gonadal function compared with cyclophosphamide regimens. Cyclophosphamide plus corticosteroids could represent the induction agents of choice in patients with severe lupus nephritis, whereas MMF could be used as an induction agent in patients with mild disease, patients who wish to preserve fertility and those at high risk of infections. However, given the complexity of disease activity in patients with lupus nephritis, the initial treatment options need to be individualized and altered based on the subsequent treatment response. Ongoing clinical trials will provide further evidence.