Treatment of lupus nephritis: current paradigms and emerging strategies

Lupus nephritis is the most common organ-threatening manifestation of lupus and continues to result in end-stage renal disease. This review describes the contemporary treatment of lupus nephritis as well as emerging therapeutic strategies.

Lupus nephritis management consists of an initial (induction) phase and a maintenance (extended) phase in which steroids are used in combination with another immunosuppressive medication. Current treatments are incompletely effective and associated with substantial toxicity. Despite disappointing results of several recent trials, novel therapies targeting diverse immunologic pathways are being actively studied in lupus nephritis. Two promising strategies include the use of B-cell depletion therapy and multitarget therapy with calcineurin inhibitors. In parallel with the conduct of these trials, there are ongoing efforts to improve trial design. Two recent studies of outcome measures reported that a level of proteinuria of less than 0.7-0.8 g at 12 months is most predictive of good long-term renal outcome, and that the inclusion of urine red blood cells worsens the predictive value of proteinuria alone.

Improved understanding of lupus nephritis pathogenesis, development of novel therapies, and optimization of clinical trial design are leading the path forward for successful drug development in lupus nephritis. The ultimate goal of these efforts is to treat our patients in a more strategic, personalized manner that improves long-term outcomes.