#2-13E. Lupus Nephritis Management: The Shift to Multi-Agent Continuous Therapy (Nat Rev Dis Primers, 2025)

How should clinicians optimize treatment strategies to combat irreversible kidney failure in patients with systemic lupus erythematosus? Lupus Nephritis (LN) is a prevalent and severe complication of SLE, affecting 25–60% of patients and often leading to irreversible chronic kidney disease. This comprehensive Primer details the disease pathobiology, emphasizing complex immune dysregulation driven by pathways such as Type I interferon signaling and calcineurin activation. The most crucial clinical development is the paradigm shift towards multi-agent regimens—integrating newer targeted therapies like belimumab, voclosporin, or obinutuzumab with standard immunosuppressants—which have demonstrated superior complete renal response rates compared to conventional dual therapy. This continuous approach effectively blurs the traditional induction/maintenance distinction. However, clinicians must acknowledge the major limitation that the current ISN/RPS histological classification remains glomerulocentric, potentially overlooking the crucial prognostic information held within the tubulointerstitial compartment. Mastering these latest composite immunosuppressive regimens and integrating them with holistic, multidisciplinary care, which meticulously addresses both immunological activity and critical non-immune factors like hypertension and adherence, is vital for maximizing kidney lifespan and improving long-term outcomes for patients with LN.

Citation: Parodis, I. et al. Lupus nephritis. nature reviews disease primers. 2025. DOI: 10.1038/s41572-025-00653-y

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