Use of a Targeted Urine Proteome Assay (TUPA) to identify protein biomarkers of delayed recovery after kidney transplant

Kenneth R. Williams; Christopher M. Colangelo; Lin Hou; Lisa Chung; Justin M. Belcher; Thomas Abbott; Isaac E. Hall; Hongyu Zhao; Lloyd G. Cantley; Chirag R. Parikh

doi:10.1002/prca.201600132

Use of a Targeted Urine Proteome Assay (TUPA) to identify protein biomarkers of delayed recovery after kidney transplant

Kenneth R. Williams, Christopher M. Colangelo, Lin Hou, Lisa Chung, Justin M. Belcher, Thomas Abbott, Isaac E. Hall, Hongyu Zhao, Lloyd G. Cantley, Chirag R. Parikh

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Purpose: Development of delayed graft function (DGF) following kidney transplant is associated with poor outcomes. An ability to rapidly identify patients with DGF versus those with immediate graft function (IGF) may facilitate the treatment of DGF and the research needed to improve prognosis. The purpose of this study was to use a Targeted Urine Proteome Assay to identify protein biomarkers of delayed recovery from kidney transplant. Experimental design: Potential biomarkers were identified using the Targeted Urine Proteome (MRM) Assay to interrogate the relative DGF/IGF levels of expression of 167 proteins in urine taken 12–18 h after kidney implantation from 21 DGF, 15 SGF (slow graft function), and 16 IGF patients. An iterative Random Forest analysis approach evaluated the relative importance of each biomarker, which was then used to identify an optimum biomarker panel that provided the maximum sensitivity and specificity with the least number of biomarkers. Conclusions and clinical relevance: Four proteins were identified that together distinguished DGF with a sensitivity of 77.4%, specificity of 82.6%, and AUC of 0.891. This panel represents an important step toward identifying DGF at an early stage so that more effective treatments can be developed to improve long-term graft outcomes.

Original language	English (US)
Article number	1600132
Journal	Proteomics - Clinical Applications
Volume	11
Issue number	7-8
DOIs	https://doi.org/10.1002/prca.201600132
State	Published - Jul 2017
Externally published	Yes

Keywords

Disease biomarkers
Kidney transplant
Targeted proteomics
Urine

ASJC Scopus subject areas

Clinical Biochemistry

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10.1002/prca.201600132

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@article{8a09622eaa9a4fc3bfb695e955ecb0f1,

title = "Use of a Targeted Urine Proteome Assay (TUPA) to identify protein biomarkers of delayed recovery after kidney transplant",

abstract = "Purpose: Development of delayed graft function (DGF) following kidney transplant is associated with poor outcomes. An ability to rapidly identify patients with DGF versus those with immediate graft function (IGF) may facilitate the treatment of DGF and the research needed to improve prognosis. The purpose of this study was to use a Targeted Urine Proteome Assay to identify protein biomarkers of delayed recovery from kidney transplant. Experimental design: Potential biomarkers were identified using the Targeted Urine Proteome (MRM) Assay to interrogate the relative DGF/IGF levels of expression of 167 proteins in urine taken 12–18 h after kidney implantation from 21 DGF, 15 SGF (slow graft function), and 16 IGF patients. An iterative Random Forest analysis approach evaluated the relative importance of each biomarker, which was then used to identify an optimum biomarker panel that provided the maximum sensitivity and specificity with the least number of biomarkers. Conclusions and clinical relevance: Four proteins were identified that together distinguished DGF with a sensitivity of 77.4%, specificity of 82.6%, and AUC of 0.891. This panel represents an important step toward identifying DGF at an early stage so that more effective treatments can be developed to improve long-term graft outcomes.",

keywords = "Disease biomarkers, Kidney transplant, Targeted proteomics, Urine",

author = "Williams, {Kenneth R.} and Colangelo, {Christopher M.} and Lin Hou and Lisa Chung and Belcher, {Justin M.} and Thomas Abbott and Hall, {Isaac E.} and Hongyu Zhao and Cantley, {Lloyd G.} and Parikh, {Chirag R.}",

note = "Funding Information: The research described in this publication was supported in part by NIH grants UL1 RR024139, S10RR026707, P30 DK079310, and P30 DK090744 (L.G.C.). We thank Jean Kanyo and Mary LoPresti for technical assistance with mass spectrometry and sample preparation, respectively. Dr. Parikh was supported by NIH grant K24DK090203. This work was also supported in part by an award from the American Heart Association (I.E.H.). Publisher Copyright: {\textcopyright} 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim",

year = "2017",

month = jul,

doi = "10.1002/prca.201600132",

language = "English (US)",

volume = "11",

journal = "Proteomics - Clinical Applications",

issn = "1862-8346",

publisher = "Wiley-VCH Verlag",

number = "7-8",

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TY - JOUR

T1 - Use of a Targeted Urine Proteome Assay (TUPA) to identify protein biomarkers of delayed recovery after kidney transplant

AU - Williams, Kenneth R.

AU - Colangelo, Christopher M.

AU - Hou, Lin

AU - Chung, Lisa

AU - Belcher, Justin M.

AU - Abbott, Thomas

AU - Hall, Isaac E.

AU - Zhao, Hongyu

AU - Cantley, Lloyd G.

AU - Parikh, Chirag R.

N1 - Funding Information: The research described in this publication was supported in part by NIH grants UL1 RR024139, S10RR026707, P30 DK079310, and P30 DK090744 (L.G.C.). We thank Jean Kanyo and Mary LoPresti for technical assistance with mass spectrometry and sample preparation, respectively. Dr. Parikh was supported by NIH grant K24DK090203. This work was also supported in part by an award from the American Heart Association (I.E.H.). Publisher Copyright: © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

PY - 2017/7

Y1 - 2017/7

N2 - Purpose: Development of delayed graft function (DGF) following kidney transplant is associated with poor outcomes. An ability to rapidly identify patients with DGF versus those with immediate graft function (IGF) may facilitate the treatment of DGF and the research needed to improve prognosis. The purpose of this study was to use a Targeted Urine Proteome Assay to identify protein biomarkers of delayed recovery from kidney transplant. Experimental design: Potential biomarkers were identified using the Targeted Urine Proteome (MRM) Assay to interrogate the relative DGF/IGF levels of expression of 167 proteins in urine taken 12–18 h after kidney implantation from 21 DGF, 15 SGF (slow graft function), and 16 IGF patients. An iterative Random Forest analysis approach evaluated the relative importance of each biomarker, which was then used to identify an optimum biomarker panel that provided the maximum sensitivity and specificity with the least number of biomarkers. Conclusions and clinical relevance: Four proteins were identified that together distinguished DGF with a sensitivity of 77.4%, specificity of 82.6%, and AUC of 0.891. This panel represents an important step toward identifying DGF at an early stage so that more effective treatments can be developed to improve long-term graft outcomes.

AB - Purpose: Development of delayed graft function (DGF) following kidney transplant is associated with poor outcomes. An ability to rapidly identify patients with DGF versus those with immediate graft function (IGF) may facilitate the treatment of DGF and the research needed to improve prognosis. The purpose of this study was to use a Targeted Urine Proteome Assay to identify protein biomarkers of delayed recovery from kidney transplant. Experimental design: Potential biomarkers were identified using the Targeted Urine Proteome (MRM) Assay to interrogate the relative DGF/IGF levels of expression of 167 proteins in urine taken 12–18 h after kidney implantation from 21 DGF, 15 SGF (slow graft function), and 16 IGF patients. An iterative Random Forest analysis approach evaluated the relative importance of each biomarker, which was then used to identify an optimum biomarker panel that provided the maximum sensitivity and specificity with the least number of biomarkers. Conclusions and clinical relevance: Four proteins were identified that together distinguished DGF with a sensitivity of 77.4%, specificity of 82.6%, and AUC of 0.891. This panel represents an important step toward identifying DGF at an early stage so that more effective treatments can be developed to improve long-term graft outcomes.

KW - Disease biomarkers

KW - Kidney transplant

KW - Targeted proteomics

KW - Urine

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JO - Proteomics - Clinical Applications

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IS - 7-8

M1 - 1600132

ER -

Use of a Targeted Urine Proteome Assay (TUPA) to identify protein biomarkers of delayed recovery after kidney transplant

Abstract

Keywords

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