Factor Xa inhibitor, edoxaban ameliorates renal injury after subtotal nephrectomy by reducing epithelial‐mesenchymal transition and inflammatory response

• DOI: 10.14814/phy2.15218
• Publication Date: 2022-03-09T10:49:42Z
• Authors: Lixin Fang; Koji Ohashi; Hayato Ogawa; Naoya Otaka; Hiroshi Kawanishi; Tomonobu Takikawa; Yuta Ozaki; Kunihiko Takahara; Minako Tatsumi; Mikito Takefuji; Toyoaki Murohara; Noriyuki Ouchi
• Keywords: Edoxaban

Chronic kidney disease (CKD) is an increasing and life-threatening worldwide. Recent evidence indicates that blood coagulation factors promote renal dysfunction in CKD patients. Activated factor X (FXa) inhibitors are safe first-line drugs for the prevention of thrombosis patients with atrial fibrillation. Here, we investigated therapeutic effects edoxaban on using mouse 5/6 nephrectomy model. Eight-week-old wild-type mice were subjected to surgery randomly assigned two groups, or vehicle admixture diet. Edoxaban treatment led reduction urinary albumin excretion plasma UN levels compared group, which was accompanied reduced glomerular cross-sectional area cell number. also attenuated fibrinogen positive remnant kidneys after subtotal nephrectomy. Moreover, resulted tubulointerstitial fibrosis nephrectomy, by expression epithelial-mesenchymal transition (EMT) markers, inflammatory mediators, oxidative stress markers kidneys. Treatment cultured proximal tubular cells, HK-2 FXa protein increased EMT abolished pretreatment edoxaban. cells FXa-stimulated phosphorylation extracellular signal-regulated kinase (ERK) NF-κB. Our findings indicate can improve injury reducing response, suggesting inhibition could be a novel target