MP06-10 THE ACTIVATION OF INFLAMMATION AMPLIFIER IN KIDNEY TRANSPLANT GRAFT AND URINARY BIOMARKER FOR CHRONIC REJECTION

Abstract

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery I1 Apr 2017MP06-10 THE ACTIVATION OF INFLAMMATION AMPLIFIER IN KIDNEY TRANSPLANT GRAFT AND URINARY BIOMARKER FOR CHRONIC REJECTION Haruka Higuchi, Daiki Iwami, Kiyohiko Hotta, Nobuo Shinohara, and Masaaki Murakami Haruka HiguchiHaruka Higuchi More articles by this author , Daiki IwamiDaiki Iwami More articles by this author , Kiyohiko HottaKiyohiko Hotta More articles by this author , Nobuo ShinoharaNobuo Shinohara More articles by this author , and Masaaki MurakamiMasaaki Murakami More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.255AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Inflammation amplifier (IA), a local chemokine inducer in non-immune cells is induced by the simultaneous activation of NF?B and STATs (IL-17, TNFa, and IL-6) and leads to a synergistic production of chemokines, growth factors, and cytokines. IA was essential for the development of inflammation in various autoimmune disease models. More recently, IA was critical for the development of chronic rejections both in murine models and human allogeneic lung transplantations (J Immunol. 189, 1928 and Int. Immunol. 25, 319). The status of IA can be a new biomarker and its regulator can be a new therapeutic target in rejected kidney allografts (KA). The objective of this study was to investigate the contribution of IA during the rejection process in KA and to identify genes regulating IA. METHODS Primary human kidney cells (PHKC) were stimulated with IL-17, IL-6, TNFa, and expressions of chemokines and IL-6 were measured by RT-PCR. Among the genes highly expressed in PHKC with IA activation, we focused on a gene named Renal NFkB Enhancer-1 (RNE1). A deficiency of RNE1 suppressed chemokines and IL-6 after IA activation in PHKC, indicating that RNE1 might be a positive regulator in IA. In another experiment, urinary RNE1 in kidney transplant recipients (KTR) were measured by ELISA and clinical data (serum creatinine, CRP, urinary protein, urinary albumin, urinary NAG, and eGFR) were also compared among the KTR patient groups with normal histology, interstitial fibrosis and tubular atrophy (IF/TA), or chronic active antibody-mediated rejection (CAAMR). RESULTS PHKC expressed excess amounts of chemokines and IL-6 after IA activation by IL-17, IL-6, and TNFa. Urinary RNE1 in KTR showed significantly higher amount in CAAMR patients (48606 ng/mgCre, n=9) compared to IF/TA (10744 ng/mgCre, n=21) and normal (6081 ng/mgCre, n=13). In contrast, serum creatinine, CRP, eGFR, U-NAG levels showed no significant difference among patient groups. CONCLUSIONS IA was activated in PHKC, and urinary RNE1 was elevated in rejected KA. These results suggested that activation of IA is involved in KA rejection, and RNE1 could be a new biomarker. Now, we are planning to examine detailed molecular mechanisms how RNE1 regulates NF-kB pathway in kidney cells and to examine if it will be a new therapeutic target for allogeneic kidney transplantations. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e76 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Haruka Higuchi More articles by this author Daiki Iwami More articles by this author Kiyohiko Hotta More articles by this author Nobuo Shinohara More articles by this author Masaaki Murakami More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...