PT2:02 Plasma metabolomic profiling reveals serine-centered immunometabolic modulation by SGLT2 inhibition in lupus nephritis

Objectives Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE), leading to chronic kidney damage and increased mortality. Metabolomic studies have revealed persistent mitochondrial and energy metabolism abnormalities in LN, even during remission. In LN, sodium–glucose cotransporter-2 (SGLT2) inhibition has been associated with reduced proteinuria, improved glomerular filtration rate, and attenuation of inflammatory and oxidative pathways. Experimental studies further indicate that dapagliflozin and related agents may modulate immune–metabolic axes, including IL-1 signaling, NLRP3 inflammasome activity, and mitochondrial function. This pilot study aimed to characterize plasma metabolic alterations across SLE renal phenotypes and to explore potential immunometabolic effects of dapagliflozin in lupus nephritis.Methods Thirty-six female SLE patients were stratified into four subgroups: active LN (n=8), inactive LN without SGLT2 inhibitor therapy (n=10), inactive LN treated with dapagliflozin (n=10), and inactive non-LN SLE (n=8). All LN cases were biopsy-proven ISN/RPS class III, IV, or pure class V nephritis. Fasting plasma samples were analyzed using untargeted gas chromatography–mass spectrometry (GC–MS). Data were normalized by log-transformation and Pareto scaling. Principal component analysis (PCA) and pathway enrichment analysis (MetaboAnalyst 5.0, KEGG database) were used to identify distinct metabolic signatures among groups.Results Inactive LN patients demonstrated differential regulation of tricarboxylic acid (TCA) cycle intermediates, fatty-acid β-oxidation, and branched-chain amino acids (p