A L Nogare1, G Joelsons, J A R Pedroso, F J V Veronese, L F Gonçalves, R C Manfro. 1. Division of Nephrology, Hospital de Clínicas de Porto Alegre and Post-Graduate Medical Sciences Course, School of Medicine, Federal University of Rio Grande do Sul, Ramiro Barcelos Avenue, Porto Alegre, RS 90035-903. Brazil
Abstract
BACKGROUND: Kidney injury molecule-1 (KIM-1), a type I transmembrane protein that is not expressed in normal renal tissue, shows increased expression in dedifferentiated cells within damaged regions of the proximal tubule. We evaluated mRNA transcription of the KIM-1 gene in renal tissue of kidney transplant patients who were experiencing graft dysfunction searching for an accurate biomarker of kidney graft injury. PATIENTS AND METHODS: mRNA analysis was performed on 59 biopsies from kidney transplant patients who had been classified according to the Banff 1997 scheme. Biopsies were categorized in 5 diagnostic groups: acute tubular necrosis (ATN) with superimposed acute rejection episode (ARE), ATN; ARE; calcineurin inhibitor nephrotoxicity (CIN); or interstitial fibrosis and tubular atrophy (IFTA). Amplified tissue RNA was quantified by real-time polymerase chain reaction. RESULTS: Renal tissue evaluations showed significantly increased KIM-1 mRNA expression as shown by median values, 25-75 percentiles, and averages of the logarithmic transformation: namely, CIN group (50.6; 1.8-285, 1; 1.24) and IFTA group (7.5; 1.26-14.6; 0.62), displayed significant differences (P > .05). In contrast, expression was lower among the ATN (0.47; 0.28-1.06; -0.13); ARE (0.21; 0.11-0.78; -0.45), and ATN+ARE (0.46; 0.06-3.27; -0.25) cohorts. CONCLUSION: These preliminary data suggested that KIM-1 mRNA might be useful biomarker of tubular damage associated with CIN and IFTA. Copyright (c) 2010 Elsevier Inc. All rights reserved.
BACKGROUND:Kidney injury molecule-1 (KIM-1), a type I transmembrane protein that is not expressed in normal renal tissue, shows increased expression in dedifferentiated cells within damaged regions of the proximal tubule. We evaluated mRNA transcription of the KIM-1 gene in renal tissue of kidney transplant patients who were experiencing graft dysfunction searching for an accurate biomarker of kidney graft injury. PATIENTS AND METHODS: mRNA analysis was performed on 59 biopsies from kidney transplant patients who had been classified according to the Banff 1997 scheme. Biopsies were categorized in 5 diagnostic groups: acute tubular necrosis (ATN) with superimposed acute rejection episode (ARE), ATN; ARE; calcineurin inhibitornephrotoxicity (CIN); or interstitial fibrosis and tubular atrophy (IFTA). Amplified tissue RNA was quantified by real-time polymerase chain reaction. RESULTS: Renal tissue evaluations showed significantly increased KIM-1 mRNA expression as shown by median values, 25-75 percentiles, and averages of the logarithmic transformation: namely, CIN group (50.6; 1.8-285, 1; 1.24) and IFTA group (7.5; 1.26-14.6; 0.62), displayed significant differences (P > .05). In contrast, expression was lower among the ATN (0.47; 0.28-1.06; -0.13); ARE (0.21; 0.11-0.78; -0.45), and ATN+ARE (0.46; 0.06-3.27; -0.25) cohorts. CONCLUSION: These preliminary data suggested that KIM-1 mRNA might be useful biomarker of tubular damage associated with CIN and IFTA. Copyright (c) 2010 Elsevier Inc. All rights reserved.
Authors: Yuxia Cui; Qihong Huang; James Todd Auman; Brian Knight; Xidong Jin; Kerry T Blanchard; Jeff Chou; Supriya Jayadev; Richard S Paules Journal: Toxicol Sci Date: 2011-08-24 Impact factor: 4.849