Drug repurposing opportunities for chronic kidney disease
Xiong Chen,
Runnan Shen,
Dongxi Zhu,
Shulu Luo,
Guochang You,
Ruijie Li,
Xiaosi Hong,
Ruijun Li,
Jihao Wu,
Yinong Huang,
Tianxin Lin
Affiliations
Xiong Chen
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Runnan Shen
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
Dongxi Zhu
School of Medicine, Sun Yat-Sen University, Guangzhou, China
Shulu Luo
Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, P.R. China
Guochang You
School of Medicine, Sun Yat-Sen University, Guangzhou, China
Ruijie Li
School of Medicine, Sun Yat-Sen University, Guangzhou, China
Xiaosi Hong
Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
Ruijun Li
Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, P.R. China
Jihao Wu
Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, P.R. China
Yinong Huang
Faculty of Medicine, Macau University of Science and Technology, Macau, China; Corresponding author
Tianxin Lin
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Clinical Research Center for Urological Diseases, Guangzhou, Guangdong, China; Corresponding author
Summary: The development of targeted drugs for the early prevention and management of chronic kidney disease (CKD) is of great importance. However, the success rates and cost-effectiveness of traditional drug development approaches are extremely low. Utilizing large sample genome-wide association study data for drug repurposing has shown promise in many diseases but has not yet been explored in CKD. Herein, we investigated actionable druggable targets to improve renal function using large-scale Mendelian randomization and colocalization analyses. We combined two population-scale independent genetic datasets and validated findings with cell-type-dependent eQTL data of kidney tubular and glomerular samples. We ultimately prioritized two drug targets, opioid receptor-like 1 and F12, with potential genetic support for restoring renal function and subsequent treatment of CKD. Our findings explore the potential pathological mechanisms of CKD, bridge the gap between the molecular mechanisms of pathogenesis and clinical intervention, and provide new strategies in future clinical trials of CKD.
