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Artificial Urinary Biomarkers for Early Diagnosis of Acute Renal Allograft Rejection
Authors:Dr Penghui Cheng  Dr Rending Wang  Dr Shasha He  Dr Pengpeng Yan  Dr Hongfeng Huang  Dr Jianghua Chen  Dr Jia Shen  Prof Kanyi Pu
Institution:1. School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, 637457 Singapore, Singapore;2. Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, P. R. China

Organ Donation and Coordination Office, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003 Zhejiang Province, P. R. China;3. Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang Province, P. R. China

Abstract:Acute renal allograft rejection (ARAR) after kidney transplantation associated with reduced graft survival and eventual graft failure is poorly diagnosed in hospitals. Here, we report the development of A rtificial bioM arker Pro bes (AMPros) for sensitive urinalysis of ARAR in murine models. AMPros spontaneously go to the kidneys after systemic administration, specifically react with the prodromal immune biomarkers to activate their near-infrared fluorescence signals to report cell-mediated rejection, and efficiently undergo renal excretion into urine. Thus, AMPros enable convenient optical urinalysis that detects ARAR prior to histological manifestation of rejection, which is also earlier than current diagnostic methods measuring proinflammatory cytokines and peripheral blood lymphocyte mRNAs. Due to the high kidney specificity, AMPros-based urinalysis discriminates allograft rejection against other non-alloimmune specific diseases, which is unattainable by measurement of serological biomarkers. Such a noninvasive and sensitive urine test holds great promise in continuous monitoring of renal allograft conditions at low resource settings for timely clinical interventions.
Keywords:Acute Allograft Rejection  Fluorescent Probes  Kidney Transplantation  Molecular Diagnosis  Noninvasive Urinalysis
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