Expert Perspective: An Approach to Refractory Lupus Nephritis

Systemic lupus erythematosus affects the kidneys in similar to 50% of all patients, and lupus nephritis (LN) is the most common manifestation of kidney involvement. 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-of-care induction regimens after 4-6 months in patients who are adherent to treatment. For patients who have LN that is truly refractory to standard of care, B cell-targeted 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. These include anti-CD38, leflunomide, intravenous immunoglobulin, plasma exchange, autologous stem cell transplantation, chimeric antigen receptor T cell therapy, anticomplement therapy, and interleukin-2 therapy.

Automated summary

Systemic lupus erythematosus affects the kidneys in about 50% of patients, with lupus nephritis being the most common manifestation of kidney involvement. Despite aggressive treatment, a significant proportion of patients are considered to have refractory lupus nephritis, with various factors contributing to poor treatment response.