Chronic Hematuria Increases Chronic Kidney Injury and Epithelial–Mesenchymal Transition in 5/6 Nephrectomy Rats

• DOI: 10.3389/fmed.2021.753506
• Publication Date: 2021-12-01T00:03:20Z
• Authors: Min Xiao; Ajay K. Medipally; Laura Biederman; Anjali A. Satoskar; Iouri Ivanov; Brad H. Rovin; Sergey V. Brodsky
• Keywords: Medicine (General); General Medicine; 3. Good health; hematuria; 03 medical and health sciences; iron; R5-920; 0302 clinical medicine; epithelial mesenchymal transition (EMT); Medicine; anticoagulation; chronic kidney disease

Chronic kidney disease (CKD) is a common outcome of many diseases. Interstitial fibrosis and tubular atrophy (IFTA) histologic hallmark CKD. Hematuria symptom in human Free hemoglobin may affect epithelial cells by generating reactive oxygen species (ROS). Epithelial-mesenchymal transition (EMT) the has been shown to play an important role IFTA development. The aim this study was determine effects chronic hematuria on CKD progression 5/6 nephrectomy (5/6NE) rat model NE rats were treated with oral warfarin (0.5 mg/kg/day) or vehicle (control). animals monitored for 26 weeks, while prothrombin time (PT), serum creatinine (SCr), measured weekly. Staining iron, trichrome, EMT (vimentin, E-cadherin, smooth muscle actin) markers performed remnant kidneys. ROS detected kidneys protein carbonyl assay immunohistochemistry heme oxygenase 1 (HMOX1), at end study. Apoptosis TUNEL assay. Warfarin treatment resulted PT increase 1.5-2.5 times from control SCr. Histologically, warfarin-treated had more iron-positive increased as compared (42.9 ± 17% vs. 18.3 2.6%). rats. number tubules that show evidence significantly higher 5/6NE apoptotic results cells, EMT, apoptosis, prominent Our data suggest