Association of Circulating Protein Levels with Kidney Outcome and Effects of Dapagliflozin: Proteomics Analysis from DAPA-CKD

Le résumé fourni par la source

Background: We studied the progression of CKD and the effects of dapagliflozin using plasma proteomics to identify proteins involved in the pathophysiology of CKD progression and dapagliflozin's underlying mechanism. Methods: Circulating protein profiles (Olink 3072 panel) of participants from the DAPA-CKD trial, recruiting 4304 patients with CKD with and without type 2 diabetes, eGFR of 25 to 75 ml/min/1.73 m2 and a UACR of 200 to 5000 mg/g, were analyzed. Multivariable cox proportional hazard models determined the risk of baseline protein levels on the composite kidney outcome (50% eGFR decline, kidney failure, or renal death). Proteins affected by dapagliflozin compared to placebo were identified by analysis of covariance followed by Ingenuity pathway analysis. Results: Baseline protein profiles were available in 2485 (57.7%) participants; 1982 (46.1%) had both baseline and year 1 protein profiles available. WFDC2, CD27, and TNFRSF7 were the most significant proteins associated with the composite kidney outcome (Fig. 1A); reflecting pathways related to immune system, inflammation, and fibrosis. Of the 216 proteins changed by 1-year treatment with dapagliflozin compared to placebo, 49 (23%) proteins were also associated with the composite kidney outcome (Fig. 1C). Among these 49 proteins, KIM-1, CTHRC1, and NT-proBNP, were decreased after 1 year of treatment with dapagliflozin (Fig. 1B). Pathways affected by dapagliflozin were involved in interleukin production & tyrosine signaling, extracellular matrix organization, and inflammation & wound healing (Fig. 1D). Conclusion: Pathways of inflammation and fibrosis associated with kidney outcomes were targeted by dapagliflozin. These data confirm and provide new insights in the molecular effects of dapagliflozin in patients with CKD.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.