Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery

Katja M. Gist; Stuart L. Goldstein; Julia Wrona; Jeffrey A. Alten; Rajit K. Basu; David S. Cooper; Danielle E. Soranno; Jane Duplantis; Christopher Altmann; Zhiqian Gao; Sarah Faubel

doi:10.1007/s00467-017-3655-y

Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery

Katja M. Gist^*, Stuart L. Goldstein, Julia Wrona, Jeffrey A. Alten, Rajit K. Basu, David S. Cooper, Danielle E. Soranno, Jane Duplantis, Christopher Altmann, Zhiqian Gao, Sarah Faubel

^*Corresponding author for this work

Pediatrics

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

51 Scopus citations

Abstract

Background: Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) are cell-cycle arrest biomarkers that have been shown to be predictive of acute kidney injury (AKI) in critically ill adults. AKI affects a large proportion (40%) of children following cardiac surgery. The aim of this study was to describe the kinetics of TIMP-2*IGFBP-7 and test its ability to predict AKI in infants following cardiac surgery. Methods: A multicenter prospective study was performed in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) from October 2013 to January 2015. Urine samples were obtained at baseline and at 2, 6, 12, 24, 48 and 72 h after CPB initiation. TIMP-2*IGFBP-7 concentration was measured in urine samples using the Astute 140® meter to determine a risk score for AKI. This risk score is the product of TIMP-2 (ng/mL) and IGFBP-7 (ng/mL) divided by 1000. Results: A total of 94 infants with a mean age of 154.2 ± 85.7 days were enrolled in the study, of whom 31 (33%) subsequently developed AKI. The mean time to AKI diagnosis was 25 ± 7 h after CPB initiation. The concentration of TIMP-2*IGFBP-7 was significantly higher in patients with AKI at 12 h after CPB initiation relative to baseline (p = 0.006). At 12 h after CPB initiation patients with a TIMP-2*IGFBP-7 concentration of ≥0.78 had a threefold higher odds of developing AKI than those with a TIMP-2*IGFBP-7 concentration of < 0.78 (95% confidence interval 1.47–6.11, p = 0.001). Conclusion: These results demonstration that TIMP-2*IGFBP-7 concentration can be used in infants to predict subsequent serum creatinine-defined AKI following CPB.

Original language	English (US)
Pages (from-to)	1611-1619
Number of pages	9
Journal	Pediatric Nephrology
Volume	32
Issue number	9
DOIs	https://doi.org/10.1007/s00467-017-3655-y
State	Published - Sep 1 2017

Funding

Urinary TIMP-2*IGFBP-7 processing was supported by a pilot grant from the Children’s Hospital Colorado Research Institute. Special thanks to the research coordinators at each of the participating sites: Shruti Marwaha and Shalayna Woodly at Cincinnati Children’s Hospital Medical Center; Krissie Hock at Children’s of Alabama; the team of nurses in the pediatric clinical translation research center at Children’s Hospital Colorado at the University of Colorado. Finally, thanks to the Center for Acute Care Nephrology, the Heart Institute Research Core and the Division of Critical Care Medicine at Cincinnati Children’s Hospital Medical Center for their support throughout the study. A multi-center prospective observational study was performed in infants (≤1 year of age) after cardiac surgery with CPB from October 2013 to January 2015 following institutional review board approval. Informed consent was obtained from the parents, or parent, of each child included in the study. Clinical Trials Information: NCT01966237, October 17, 2013 S. Goldstein reports the following disclosures: Baxter/Gambro renal Products (grant support/expert panel/consultant); Akebia (consultant); Bellco (consultant); Otsuka (steering committee for a clinical trial); La Jolla Pharmaceuticals (teering committee for a clinical trial); Astute Medical Inc (consultant); AM Pharma (consultant); Bioporto Inc. (consultant); Reata Medical Inc. (DSMB member for a study). R. Basu is part of the speakers’ bureau for Baxter Renal Solutions and a consultant for Bioporto Diagnostics. Acknowledgments Urinary TIMP-2*IGFBP-7 processing was supported by a pilot grant from the Children’s Hospital Colorado Research Institute. Special thanks to the research coordinators at each of the participating sites: Shruti Marwaha and Shalayna Woodly at Cincinnati Children’s Hospital Medical Center; Krissie Hock at Children’s of Alabama; the team of nurses in the pediatric clinical translation research center at Children’s Hospital Colorado at the University of Colorado. Finally, thanks to the Center for Acute Care Nephrology, the Heart Institute Research Core and the Division of Critical Care Medicine at Cincinnati Children’s Hospital Medical Center for their support throughout the study.

Keywords

Acute kidney injury
Cardiac surgery
Cell cycle arrest biomarkers
Infants

ASJC Scopus subject areas

Nephrology
Pediatrics, Perinatology, and Child Health

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10.1007/s00467-017-3655-y

Cite this

Gist, K. M., Goldstein, S. L., Wrona, J., Alten, J. A., Basu, R. K., Cooper, D. S., Soranno, D. E., Duplantis, J., Altmann, C., Gao, Z., & Faubel, S. (2017). Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery. Pediatric Nephrology, 32(9), 1611-1619. https://doi.org/10.1007/s00467-017-3655-y

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abstract = "Background: Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) are cell-cycle arrest biomarkers that have been shown to be predictive of acute kidney injury (AKI) in critically ill adults. AKI affects a large proportion (40%) of children following cardiac surgery. The aim of this study was to describe the kinetics of TIMP-2*IGFBP-7 and test its ability to predict AKI in infants following cardiac surgery. Methods: A multicenter prospective study was performed in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) from October 2013 to January 2015. Urine samples were obtained at baseline and at 2, 6, 12, 24, 48 and 72 h after CPB initiation. TIMP-2*IGFBP-7 concentration was measured in urine samples using the Astute 140{\textregistered} meter to determine a risk score for AKI. This risk score is the product of TIMP-2 (ng/mL) and IGFBP-7 (ng/mL) divided by 1000. Results: A total of 94 infants with a mean age of 154.2 ± 85.7 days were enrolled in the study, of whom 31 (33%) subsequently developed AKI. The mean time to AKI diagnosis was 25 ± 7 h after CPB initiation. The concentration of TIMP-2*IGFBP-7 was significantly higher in patients with AKI at 12 h after CPB initiation relative to baseline (p = 0.006). At 12 h after CPB initiation patients with a TIMP-2*IGFBP-7 concentration of ≥0.78 had a threefold higher odds of developing AKI than those with a TIMP-2*IGFBP-7 concentration of < 0.78 (95% confidence interval 1.47–6.11, p = 0.001). Conclusion: These results demonstration that TIMP-2*IGFBP-7 concentration can be used in infants to predict subsequent serum creatinine-defined AKI following CPB.",

keywords = "Acute kidney injury, Cardiac surgery, Cell cycle arrest biomarkers, Infants",

author = "Gist, {Katja M.} and Goldstein, {Stuart L.} and Julia Wrona and Alten, {Jeffrey A.} and Basu, {Rajit K.} and Cooper, {David S.} and Soranno, {Danielle E.} and Jane Duplantis and Christopher Altmann and Zhiqian Gao and Sarah Faubel",

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AU - Gist, Katja M.

AU - Goldstein, Stuart L.

AU - Wrona, Julia

AU - Alten, Jeffrey A.

AU - Basu, Rajit K.

AU - Cooper, David S.

AU - Soranno, Danielle E.

AU - Duplantis, Jane

AU - Altmann, Christopher

AU - Gao, Zhiqian

AU - Faubel, Sarah

PY - 2017/9/1

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N2 - Background: Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) are cell-cycle arrest biomarkers that have been shown to be predictive of acute kidney injury (AKI) in critically ill adults. AKI affects a large proportion (40%) of children following cardiac surgery. The aim of this study was to describe the kinetics of TIMP-2*IGFBP-7 and test its ability to predict AKI in infants following cardiac surgery. Methods: A multicenter prospective study was performed in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) from October 2013 to January 2015. Urine samples were obtained at baseline and at 2, 6, 12, 24, 48 and 72 h after CPB initiation. TIMP-2*IGFBP-7 concentration was measured in urine samples using the Astute 140® meter to determine a risk score for AKI. This risk score is the product of TIMP-2 (ng/mL) and IGFBP-7 (ng/mL) divided by 1000. Results: A total of 94 infants with a mean age of 154.2 ± 85.7 days were enrolled in the study, of whom 31 (33%) subsequently developed AKI. The mean time to AKI diagnosis was 25 ± 7 h after CPB initiation. The concentration of TIMP-2*IGFBP-7 was significantly higher in patients with AKI at 12 h after CPB initiation relative to baseline (p = 0.006). At 12 h after CPB initiation patients with a TIMP-2*IGFBP-7 concentration of ≥0.78 had a threefold higher odds of developing AKI than those with a TIMP-2*IGFBP-7 concentration of < 0.78 (95% confidence interval 1.47–6.11, p = 0.001). Conclusion: These results demonstration that TIMP-2*IGFBP-7 concentration can be used in infants to predict subsequent serum creatinine-defined AKI following CPB.

AB - Background: Tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) are cell-cycle arrest biomarkers that have been shown to be predictive of acute kidney injury (AKI) in critically ill adults. AKI affects a large proportion (40%) of children following cardiac surgery. The aim of this study was to describe the kinetics of TIMP-2*IGFBP-7 and test its ability to predict AKI in infants following cardiac surgery. Methods: A multicenter prospective study was performed in infants undergoing cardiac surgery with cardiopulmonary bypass (CPB) from October 2013 to January 2015. Urine samples were obtained at baseline and at 2, 6, 12, 24, 48 and 72 h after CPB initiation. TIMP-2*IGFBP-7 concentration was measured in urine samples using the Astute 140® meter to determine a risk score for AKI. This risk score is the product of TIMP-2 (ng/mL) and IGFBP-7 (ng/mL) divided by 1000. Results: A total of 94 infants with a mean age of 154.2 ± 85.7 days were enrolled in the study, of whom 31 (33%) subsequently developed AKI. The mean time to AKI diagnosis was 25 ± 7 h after CPB initiation. The concentration of TIMP-2*IGFBP-7 was significantly higher in patients with AKI at 12 h after CPB initiation relative to baseline (p = 0.006). At 12 h after CPB initiation patients with a TIMP-2*IGFBP-7 concentration of ≥0.78 had a threefold higher odds of developing AKI than those with a TIMP-2*IGFBP-7 concentration of < 0.78 (95% confidence interval 1.47–6.11, p = 0.001). Conclusion: These results demonstration that TIMP-2*IGFBP-7 concentration can be used in infants to predict subsequent serum creatinine-defined AKI following CPB.

KW - Acute kidney injury

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Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery

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