Management of Refractory Lupus Nephritis

Abstract

Despite the significant advances in the field, up to one-third of lupus nephritis (LN) patients still do not respond adequately to initial immunosuppressive treatment. This group of patients is heterogeneous in terms of clinical presentation (deterioration of glomerular filtration rate, variable degrees of persistent proteinuria, active urine sediment) and the potential for reversion (ongoing kidney inflammation versus irreversible damage due to scarring and fibrosis). A repeat kidney biopsy can be highly informative in this regard and should be strongly considered. High-quality evidence regarding the treatment of refractory LN is lacking, and management is largely based on observational studies and expert opinion. Options include switching between mycophenolate mofetil (MMF) and cyclophosphamide (CYC), using rituximab as monotherapy or add-on therapy, or combining MMF with a calcineurin inhibitor in cases of persistent proteinuria. Renal response can be maintained with MMF or prolonged pulses of intravenous CYC administered bimonthly or quarterly. The efficacy of novel biological agents and those under development in refractory forms of LN remains to be determined. Tight control of cardiovascular risk factors, use of hydroxychloroquine, immunisations, and osteoporosis prophylaxis are important adjunctive measures. For the future, we anticipate that research efforts for the identification of accurate biomarkers together with accumulating data from observational and controlled studies will assist therapeutic decisions and improve outcomes in patients with refractory LN.