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Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies

Kidney toxicity accounts both for the failure of many drug candidates as well as considerable patient morbidity. Whereas histopathology remains the gold standard for nephrotoxicity in animal systems, serum creatinine (SCr) and blood urea nitrogen (BUN) are the primary options for monitoring kidney d... Full description

Journal Title: Nature biotechnology 2010-05, Vol.28 (5), p.478-485
Main Author: Vaidya, Vishal S
Other Authors: Ozer, Josef S , Sistare, Frank D , Dieterle, Frank , Collings, Fitz B , Ramirez, Victoria , Troth, Sean , Muniappa, Nagaraja , Thudium, Douglas , Gerhold, David , Holder, Daniel J , Bobadilla, Norma A , Marrer, Estelle , Perentes, Elias , Cordier, André , Vonderscher, Jacky , Maurer, Gérard , Goering, Peter L , Bonventre, Joseph V
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1087-0156
Link: https://www.ncbi.nlm.nih.gov/pubmed/20458318
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title: Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies
format: Article
creator:
  • Vaidya, Vishal S
  • Ozer, Josef S
  • Sistare, Frank D
  • Dieterle, Frank
  • Collings, Fitz B
  • Ramirez, Victoria
  • Troth, Sean
  • Muniappa, Nagaraja
  • Thudium, Douglas
  • Gerhold, David
  • Holder, Daniel J
  • Bobadilla, Norma A
  • Marrer, Estelle
  • Perentes, Elias
  • Cordier, André
  • Vonderscher, Jacky
  • Maurer, Gérard
  • Goering, Peter L
  • Bonventre, Joseph V
subjects:
  • Acetylglucosaminidase - urine
  • Animals
  • Biological markers
  • Biomarkers, Pharmacological - metabolism
  • Biomarkers, Pharmacological - urine
  • Biotechnology
  • Blood Urea Nitrogen
  • Cell Adhesion Molecules - genetics
  • Cell Adhesion Molecules - metabolism
  • Cell Adhesion Molecules - urine
  • Cisplatin - toxicity
  • Creatinine - blood
  • Cyclosporine - toxicity
  • Diagnosis
  • Drug Evaluation, Preclinical
  • Drug therapy
  • Drug-Related Side Effects and Adverse Reactions
  • Gentamicins - toxicity
  • Histocytochemistry
  • Immunoglobulins
  • Kidney - drug effects
  • Kidney - injuries
  • Kidney diseases
  • Kidney Function Tests - methods
  • Kidney Function Tests - standards
  • Male
  • Molecular biology
  • Oligonucleotide Array Sequence Analysis
  • Patient outcomes
  • Pharmacology
  • Physiological aspects
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Reperfusion Injury
  • ROC Curve
  • T cells
  • Thioacetamide - toxicity
  • Toxicity
ispartof: Nature biotechnology, 2010-05, Vol.28 (5), p.478-485
description: Kidney toxicity accounts both for the failure of many drug candidates as well as considerable patient morbidity. Whereas histopathology remains the gold standard for nephrotoxicity in animal systems, serum creatinine (SCr) and blood urea nitrogen (BUN) are the primary options for monitoring kidney dysfunction in humans. The transmembrane tubular protein kidney injury molecule-1 (Kim-1) was previously reported to be markedly induced in response to renal injury. Owing to the poor sensitivity and specificity of SCr and BUN, we used rat toxicology studies to compare the diagnostic performance of urinary Kim-1 to BUN, SCr and urinary N-acetyl-beta-D-glucosaminidase (NAG) as predictors of kidney tubular damage scored by histopathology. Kim-1 outperforms SCr, BUN and urinary NAG in multiple rat models of kidney injury. Urinary Kim-1 measurements may facilitate sensitive, specific and accurate prediction of human nephrotoxicity in preclinical drug screens. This should enable early identification and elimination of compounds that are potentially nephrotoxic.
language: eng
source:
identifier: ISSN: 1087-0156
fulltext: no_fulltext
issn:
  • 1087-0156
  • 1546-1696
url: Link


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titleKidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies
creatorVaidya, Vishal S ; Ozer, Josef S ; Sistare, Frank D ; Dieterle, Frank ; Collings, Fitz B ; Ramirez, Victoria ; Troth, Sean ; Muniappa, Nagaraja ; Thudium, Douglas ; Gerhold, David ; Holder, Daniel J ; Bobadilla, Norma A ; Marrer, Estelle ; Perentes, Elias ; Cordier, André ; Vonderscher, Jacky ; Maurer, Gérard ; Goering, Peter L ; Bonventre, Joseph V
creatorcontribVaidya, Vishal S ; Ozer, Josef S ; Sistare, Frank D ; Dieterle, Frank ; Collings, Fitz B ; Ramirez, Victoria ; Troth, Sean ; Muniappa, Nagaraja ; Thudium, Douglas ; Gerhold, David ; Holder, Daniel J ; Bobadilla, Norma A ; Marrer, Estelle ; Perentes, Elias ; Cordier, André ; Vonderscher, Jacky ; Maurer, Gérard ; Goering, Peter L ; Bonventre, Joseph V
descriptionKidney toxicity accounts both for the failure of many drug candidates as well as considerable patient morbidity. Whereas histopathology remains the gold standard for nephrotoxicity in animal systems, serum creatinine (SCr) and blood urea nitrogen (BUN) are the primary options for monitoring kidney dysfunction in humans. The transmembrane tubular protein kidney injury molecule-1 (Kim-1) was previously reported to be markedly induced in response to renal injury. Owing to the poor sensitivity and specificity of SCr and BUN, we used rat toxicology studies to compare the diagnostic performance of urinary Kim-1 to BUN, SCr and urinary N-acetyl-beta-D-glucosaminidase (NAG) as predictors of kidney tubular damage scored by histopathology. Kim-1 outperforms SCr, BUN and urinary NAG in multiple rat models of kidney injury. Urinary Kim-1 measurements may facilitate sensitive, specific and accurate prediction of human nephrotoxicity in preclinical drug screens. This should enable early identification and elimination of compounds that are potentially nephrotoxic.
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publisherUnited States: Nature Publishing Group
subjectAcetylglucosaminidase - urine ; Animals ; Biological markers ; Biomarkers, Pharmacological - metabolism ; Biomarkers, Pharmacological - urine ; Biotechnology ; Blood Urea Nitrogen ; Cell Adhesion Molecules - genetics ; Cell Adhesion Molecules - metabolism ; Cell Adhesion Molecules - urine ; Cisplatin - toxicity ; Creatinine - blood ; Cyclosporine - toxicity ; Diagnosis ; Drug Evaluation, Preclinical ; Drug therapy ; Drug-Related Side Effects and Adverse Reactions ; Gentamicins - toxicity ; Histocytochemistry ; Immunoglobulins ; Kidney - drug effects ; Kidney - injuries ; Kidney diseases ; Kidney Function Tests - methods ; Kidney Function Tests - standards ; Male ; Molecular biology ; Oligonucleotide Array Sequence Analysis ; Patient outcomes ; Pharmacology ; Physiological aspects ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Reperfusion Injury ; ROC Curve ; T cells ; Thioacetamide - toxicity ; Toxicity
ispartofNature biotechnology, 2010-05, Vol.28 (5), p.478-485
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12Marrer, Estelle
13Perentes, Elias
14Cordier, André
15Vonderscher, Jacky
16Maurer, Gérard
17Goering, Peter L
18Bonventre, Joseph V
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descriptionKidney toxicity accounts both for the failure of many drug candidates as well as considerable patient morbidity. Whereas histopathology remains the gold standard for nephrotoxicity in animal systems, serum creatinine (SCr) and blood urea nitrogen (BUN) are the primary options for monitoring kidney dysfunction in humans. The transmembrane tubular protein kidney injury molecule-1 (Kim-1) was previously reported to be markedly induced in response to renal injury. Owing to the poor sensitivity and specificity of SCr and BUN, we used rat toxicology studies to compare the diagnostic performance of urinary Kim-1 to BUN, SCr and urinary N-acetyl-beta-D-glucosaminidase (NAG) as predictors of kidney tubular damage scored by histopathology. Kim-1 outperforms SCr, BUN and urinary NAG in multiple rat models of kidney injury. Urinary Kim-1 measurements may facilitate sensitive, specific and accurate prediction of human nephrotoxicity in preclinical drug screens. This should enable early identification and elimination of compounds that are potentially nephrotoxic.
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28Patient outcomes
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30Physiological aspects
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titleKidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies
authorVaidya, Vishal S ; Ozer, Josef S ; Sistare, Frank D ; Dieterle, Frank ; Collings, Fitz B ; Ramirez, Victoria ; Troth, Sean ; Muniappa, Nagaraja ; Thudium, Douglas ; Gerhold, David ; Holder, Daniel J ; Bobadilla, Norma A ; Marrer, Estelle ; Perentes, Elias ; Cordier, André ; Vonderscher, Jacky ; Maurer, Gérard ; Goering, Peter L ; Bonventre, Joseph V
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1Animals
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5Biotechnology
6Blood Urea Nitrogen
7Cell Adhesion Molecules - genetics
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34Reperfusion Injury
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36T cells
37Thioacetamide - toxicity
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abstractKidney toxicity accounts both for the failure of many drug candidates as well as considerable patient morbidity. Whereas histopathology remains the gold standard for nephrotoxicity in animal systems, serum creatinine (SCr) and blood urea nitrogen (BUN) are the primary options for monitoring kidney dysfunction in humans. The transmembrane tubular protein kidney injury molecule-1 (Kim-1) was previously reported to be markedly induced in response to renal injury. Owing to the poor sensitivity and specificity of SCr and BUN, we used rat toxicology studies to compare the diagnostic performance of urinary Kim-1 to BUN, SCr and urinary N-acetyl-beta-D-glucosaminidase (NAG) as predictors of kidney tubular damage scored by histopathology. Kim-1 outperforms SCr, BUN and urinary NAG in multiple rat models of kidney injury. Urinary Kim-1 measurements may facilitate sensitive, specific and accurate prediction of human nephrotoxicity in preclinical drug screens. This should enable early identification and elimination of compounds that are potentially nephrotoxic.
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