Sodium-glucose cotransporter 2 inhibitors in lupus nephritis and ANCA-associated vasculitis: unmet needs to be addressed

Current treatment of severe autoimmune glomerulonephritis such as lupus nephritis (LN) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) relies primarily on immunosuppression to reduce kidney inflammation and chronic damage. However, many patients exhibit persistent proteinuria despite treatment, which serves as a prognostic biomarker for long-term outcomes. The residual proteinuria after 12 months might reflect hyperfiltration in remaining nephrons due to chronic damage rather than active inflammation, contributing to progressive kidney function deterioration. Sodium–glucose cotransporter-2 inhibitors (SGLT2i) are established drugs used to minimize chronic kidney disease (CKD) progression, demonstrating benefits beyond glycemic control. These medications reduce intraglomerular pressure, decrease albuminuria, minimize tubular workload, and exhibit anti-inflammatory properties through various mechanisms which ultimately reduce hard cardiovascular and kidney-related endpoints in large clinical trials. However, their potential role in managing LN and AAV remains unexplored because such individuals were systematically excluded from the landmark clinical trials due to concerns about immunosuppression and infection risks. In this review, we describe the mechanisms underlying of SGLT2i, explore the rationale and existing evidence gaps regarding their application and optimal timing for SGLT2i initiation in LN and AAV patients; and advocating for inclusion of these individuals in future clinical trials. Addressing these gaps could significantly improve long-term outcomes in these vulnerable populations.