WCN26-5099 EFFICACY AND SAFETY OF A TARGETED-RELEASE FORMULATION OF BUDESONIDE (HR19042 CAPSULES) IN PATIENTS WITH PRIMARY IgA NEPHROPATHY: A RANDOMIZED, DOUBLE-BLIND, MULTICENTER, PLACEBO-CONTROLLED PHASE 2/3 TRIAL

which were increased (FDRq<0.05).Empagliflozin modulated members of central metabolic pathways (carbohydrate and amino acid metabolism, e.g.GOT1), acid-base handling (carbonic anhydrase 14), markers of the lysosome and tubular epithelial transmembrane proteins.Combination therapy, finerenone plus empagliflozin, largely reflected the effects observed with either monotherapy.Here, 697 proteins were decreased, 57 increased (FDRq<0.05).Notably, the effect on coagulation and complement-related markers appeared to be amplified in the combination arm.In pathway analyses, complement and coagulation cues were suppressed with finerenone, whereas empagliflozin monotherapy was associated with an increase in metabolic pathways. Conclusion:This study sheds insights into the dynamics of the urine proteome in patients with T2D and CKD treated with finerenone in combination with SGLT2 inhibition.It provides hypotheses on how both drugs confer renoprotection warranting further mechanistic investigation.Finerenone and empagliflozin appear to act synergistically on distinct pathways: finerenone may alter remodeling and complement-driven inflammatory cues while empagliflozin may optimize metabolic workload, thereby slowing CKD progression.I have potential conflict of interest to disclose.