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Mingyue Xu,* Chunlin Zhang,* Linlin Zhang, Hua Qu, Yuren Wang Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, Second Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hua Qu; Yuren Wang, Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, the Second Affiliated Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +86 2368763255, Fax +86 2368755707, Email quhuahua120@163.com; 346577395@qq.comPurpose: To explore the expression of asprosin in subjects with pre-DKD and DKD and to analyze its relationship with kidney injury, inflammation, and glucose and lipid metabolism.Methods: Based on urine albumin:creatinine ratio (UACr), participants were divided into DM, pre-DKD, and DKD groups. Relevant human physiological and biochemical parameters were detected in the three groups.Results: We found relatively higher levels of asprosin in both pre-DKD and DKD groups than the DM group. Moreover, data from the Nephroseq database support increased gene expression of asprosin in kidney tissue from DKD patients. Further correlation analysis revealed that the plasma asprosin level was positively correlated with age, waist circumference, waist:hip ratio, systolic blood pressure, creatinine, UACr, triglycerides, HDL-c, fasting insulin, HOMA-IR, and the inflammatory marker G3P and negatively associated with eGFR. Multiple logistical regression analysis showed that asprosin concentration was significantly associated with pre-DKD and DKD after adjusting for sex, age, BMI, WHR, and HOMA-IR, while this correlation was lost after controlling for G3P.Conclusion: Plasma asprosin is associated with kidney injury in diabetic conditions, and this association might be connected through inflammatory response. Further studies are needed to assess the role and mechanism of asprosin in DKD.Keywords: asprosin, diabetes, diabetic kidney disease, kidney injury

Xuedong Yin,1,2,* Qiaoling Yang,1,* Hongjing Li,1,3,* Yulin Kang,4 Zhiling Li1 1Department of Pharmacy, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, People’s Republic of China; 2School of Medicine, Shanghai Jiao Tong University, Shanghai, 200125, People’s Republic of China; 3Department of Pediatrics, Hunan Children’s Hospital, Changsha, 410007, People’s Republic of China; 4Department of Nephrology and Rheumatology, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhiling Li, Department of Pharmacy, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, 355 Luding Road, Putuo District, Shanghai, 200062, People’s Republic of China, Email lzhiling2001@126.com Yulin Kang, Department of Nephrology and Rheumatology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, 355 Luding Road, Putuo District, Shanghai, 200062, People’s Republic of China, Email kangyu.lin@yandex.comBackground: Vancomycin (VCM) has long been used clinically to fight against Gram-positive bacterial infections. In recent decades, an increased number of kidney injury cases caused by VCM overdose have been reported. In this study, we further investigated the mechanism of VCM-overdose-induced kidney injury.Methods: Immunohistochemistry (IHC) staining, RT-qPCR and Western blot assays were used to determine ki67, DDX5, PTGS2, GPX4 and SLC7A11 expressions in the kidney tissues of mice. CCK-8 and flow cytometry assays were used to determine HK2 cell viability and apoptosis. In addition, RT-qPCR and Western blot assays was applied to evaluate the expressions of ACSL4, PTGS2, GPX4, SLC7A11, DDX5 and Ki67 in HK2 cells.Results: We found that VCM induced ferroptosis in vitro and in vivo. Ferrostatin-1 (Fer-1) is a potent inhibitor of ferroptosis, Fer-1 rescued cell viability and renal function renal morphology in VCM-treated cells and mice, respectively. Further, GPX4, which plays an essential role in reducing lipid hydroperoxides and preventing ferroptosis, was observed to be downregulated by VCM treatment. Interestingly, we found that GPX4-knockdown HK-2 cells exhibited a similar phenotype and gene expression level of ACSL4, PTGS2, DDX5 and Ki67 compared with VCM-treated cells, which suggested that VCM could induce ferroptosis in HK2 cells by down-regulating GPX4.Conclusion: In conclusion, VCM induced renal injury in the kidney tissues of mice. In addition, VCM induced ferroptosis cell death in HK-2 cells and in the kidney tissues of mice by down-regulating GPX4 and causing the accumulation of peroxides. These data suggested that VCM could induce renal injury in vitro and in vivo via triggering ferroptosis. This study further elucidates the mechanism of VCM-induced renal injury and provides additional references for clinical use of VCM.Keywords: vancomycin, ferroptosis, glutathione peroxidase 4, reactive oxygen species, kidney injury