Despite the continuing development of immunomodulatory agents and supportive care, the prognosis associated with lupus nephritis (LN) has not improved substantially in the past decade, with end-stage kidney disease still developing in 5–30% of patients within 10 years of LN diagnosis. Moreover, inter-ethnic variation in the tolerance of, clinical response to and level of evidence regarding various therapeutic regimens for LN has led to variation in treatment prioritization in different international recommendations. Modalities that better preserve kidney function and reduce the toxicities of concomitant glucocorticoids are unmet needs in the development of therapeutics for LN. In addition to the conventional recommended therapies for LN, there are newly approved treatments as well as investigational drugs in the pipeline, including the newer generation calcineurin inhibitors and biologic agents. In view of the heterogeneity of LN in terms of clinical presentation and prognosis, the choice of therapies depends on a number of clinical considerations. Molecular profiling, gene-signature fingerprints and urine proteomic panels might enhance the accuracy of patient stratification for treatment personalization in the future.
The development of novel therapeutics to improve the efficacy-to-toxicity balance for lupus nephritis (LN) has unmet needs.
Inter-ethnic variation in tolerance to, efficacy of and evidence level for various conventional treatment regimens for LN has led to differences in prioritization in national and international guidelines.
Belimumab and voclosporin are the two most recently approved drugs for the treatment of LN in most parts of the world.
New-generation anti-CD20 biologic agents, type I interferon antagonists and rituximab–belimumab combination regimens show promise for the treatment of LN.
Molecular profiling, gene-signature fingerprints and urine proteomic panels could enhance the accuracy of patient stratification for treatment personalization.
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Y.K.O.T. received an unrestricted research grant from GlaxoSmithKline, Aurinia Pharmaceuticals and Vifor Pharma. The Leiden University Medical Center received consulting fees for consultancy provided by Y.K.O.T. from Aurinia Pharmaceuticals, GlaxoSmithKline, KezarBio, Novartis, Otsuka Pharmaceuticals and Vifor Pharma. Y.T. has received speaking fees and/or honoraria from AbbVie, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Gilead, GlaxoSmithKline, Mitsubishi-Tanabe and Pfizer, and has received research grants from AbbVie, Asahi-Kasei, Boehringer-Ingelheim, Chugai, Daiichi-Sankyo, Eisai and Takeda. The remaining authors declare no competing interests.
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Mok, C.C., Teng, Y.K.O., Saxena, R. et al. Treatment of lupus nephritis: consensus, evidence and perspectives. Nat Rev Rheumatol 19, 227–238 (2023). https://doi.org/10.1038/s41584-023-00925-5