Management of refractory lupus nephritis: challenges and solutions

Refractory lupus nephritis, broadly defined as failure to attain clinical remission after appropriate induction immunosuppressive therapy, is associated with an increased risk of progression to end-stage kidney disease and mortality. This is a challenging issue in clinical practice, as modern induction therapy despite proven efficacy can still be associated with treatment failure. Moreover, newer therapies have failed in recent years to displace or even match existing protocols for effective induction of remission. Refractory disease is generally assessed on the basis of clinical parameters, which may be unreliable, and renal biopsy, which is often not performed in a standard or timely fashion. Persisting histological inflammation in 30%–50% of patients who have attained clinical remission highlights the disparity between clinical and immunological response to therapy. The lack of an international consensus regarding what constitutes refractory lupus nephritis compounds clinician indecision regarding optimal management for these patients. Moreover, non-adherence to prescribed therapy versus primary treatment failure can be challenging to discriminate, and the time point at which non-response becomes treatment failure is unclear. In this review, we assess the key published evidence for the treatment of refractory lupus nephritis and provide practical recommendations based around the use of adjunctive therapies. These agents include rituximab and calcineurin inhibitors, with evidence consisting largely of observational or uncontrolled studies, as well as some of the biologic therapies currently under investigation through prospective clinical trials. The poor prognosis of refractory lupus nephritis demands regular review of patient response and the flexibility to switch or augment therapy.