To summarize the therapeutic options for proliferative and membranous lupus nephritis that is resistant to conventional treatment.

Treatment trials in human lupus nephritis from years 1985 to 2005 that have been published in the English literature were searched by Medline using the keywords “lupus,” “nephritis,” “glomerulonephritis,” “renal,” “refractory,” “resistant,” “recalcitrant,” “cyclophosphamide,” “mycophenolate,” “cyclosporin,” “tacrolimus,” “leflunomide,” “intravenous immunoglobulin,” “apheresis,” “plasmapheresis,” “immunoadsorption,” “marrow transplantation,” “stem cell transplantation,” “immunoablative,” “rituximab,” and “biologics.” Laboratory, histological, and nonrenal lupus studies were excluded.

There is no universal definition of treatment resistance in lupus nephritis. Controlled trials in refractory lupus nephritis are largely unavailable. Open-labeled studies have reported success of newer immunosuppressive drugs, immunomodulatory therapies, and the biological agents such as mycophenolate mofetil (MMF), calcineurin inhibitors, leflunomide, intravenous immunoglobulin, immunoadsorption, and rituximab in the treatment of cyclophosphamide (CYC) resistant proliferative lupus nephritis. More aggressive CYC regimens have been used in lupus nephritis, but at the expense of more toxicities. For membranous lupus nephritis (MLN), a combination of corticosteroids with either azathioprine, chlorambucil, cyclosporin A, MMF, or CYC is initially effective in two-thirds of patients. More aggressive and costly regimens should be reserved for truly refractory disease with persistent nephrotic syndrome or declining renal function. Evidence regarding the efficacy of MMF in refractory MLN is conflicting and controlled trials are necessary to resolve the controversy.

The treatment of refractory lupus nephritis remains anecdotal. An international consensus in the renal response criteria should be developed and validated so that controlled trials can be performed to compare the efficacy of various treatment modalities.