Objective: To review the literature available regarding treatment of lupus nephritis (LN) refractory to cyclophosphamide, mycophenolate mofetil, azathioprine, and glucocorticoids. Data Sources: PubMed-MEDLINE and SCOPUS databases were searched through June 2013 using the terms lupus nephritis, refractory, induction, systemic lupus erythematosus, diffuse proliferative glomerulonephritis, rituximab, cyclosporine, tacrolimus, leflunomide, mizoribine, intravenous immunoglobulin, and belimumab. Study Selection and Data Extraction: Included studies were limited to human studies that evaluated clinical efficacy and English language articles. Articles assessing treatment with first-line agents such as glucocorticoids, cyclophosphamide, mycophenolate, and azathioprine were excluded from this review. Data Synthesis: There are an increasing number of medications being used in refractory LN, making the selection of an appropriate agent more difficult. Thirty studies evaluating the treatment of LN with alternative agents were identified. Although rituximab and calcineurin inhibitors have demonstrated the ability to induce remission in approximately 60 of patients with LN, large randomized trials have not confirmed these results. Leflunomide, mizoribine, and intravenous immunoglobulin have revealed potential benefits in some patient populations; however, there is not enough data to support the regular use of these agents for refractory LN. Conclusions: Rituximab and calcineurin inhibitors have the most evidence to support their use and should be the preferred agents in the treatment of refractory LN at this time. Further studies may elucidate the efficacy of other agents for refractory LN.
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