Drugs. 2026 May 14. doi: 10.1007/s40265-026-02337-7. Online ahead of print.
ABSTRACT
Lupus nephritis (LN) remains a major cause of morbidity and progression to chronic kidney disease in systemic lupus erythematosus. Beyond immunosuppression, emerging evidence highlights the critical role of nephron-protective therapies in mitigating chronic damage and preserving renal function. This narrative review included a structured literature search in PubMed, EMBASE, and Web of Science for new cardio-renoprotective therapies in LN. Agents targeting metabolic, hemodynamic, and inflammatory pathways, including sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and nonsteroidal mineralocorticoid receptor antagonists (ns-MRAs), have shown renal and cardiovascular benefits in proteinuric and diabetic populations, and recent data suggest potential efficacy in LN. These therapies reduce intraglomerular pressure, proteinuria, oxidative stress, and tubular inflammation, complementing the immunomodulatory effects of standard regimens. In addition, endothelin receptor antagonists and novel anti-fibrotic or metabolic modulators are under investigation for synergistic cardiorenal protection. Early integration of these agents may delay progression to end-stage kidney disease, improve systemic vascular health, and reduce long-term treatment burden. Future randomized trials specifically designed in LN cohorts are warranted to define optimal timing, combinations, and safety in the context of immunosuppression. Nephron-protective therapy represents a paradigm shift in LN management, from solely controlling autoimmunity toward preserving long-term renal structure and function through multi-system, cardio-renal protection.
PMID:42133281 | DOI:10.1007/s40265-026-02337-7