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Despite prompt diagnosis and treatment with aggressive immunosuppression, a significant proportion of LN patients do not respond to treatment and are considered to have refractory LN. Several factors other than drug resistance, such as nonadherence to treatment, undertreatment with conventional drugs, the effects of accumulated chronic damage, and genetic factors, may contribute to a poor response to treatment and should be considered. We define refractory LN as no change in (or worsening of) proteinuria and\/or estimated glomerular filtration rate in response to 2 different standard\u2010of\u2010care induction regimens after 4\u20136 months in patients who are adherent to treatment. For patients who have LN that is truly refractory to standard of care, B cell\u2013targeted therapy, specifically rituximab (RTX), is the most common next step. There is limited evidence available on alternative rescue therapies that may be used when there is no response to RTX. 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