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Published in: Critical Care 1/2019

Open Access 01-12-2019 | Acute Kidney Injury | Research

Clinical use of [TIMP-2]•[IGFBP7] biomarker testing to assess risk of acute kidney injury in critical care: guidance from an expert panel

Authors: Louis M. Guzzi, Tobias Bergler, Brian Binnall, Daniel T. Engelman, Lui Forni, Michael J. Germain, Eric Gluck, Ivan Göcze, Michael Joannidis, Jay L. Koyner, V. Seenu Reddy, Thomas Rimmelé, Claudio Ronco, Julien Textoris, Alexander Zarbock, John A. Kellum

Published in: Critical Care | Issue 1/2019

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Abstract

Background

The first FDA-approved test to assess risk for acute kidney injury (AKI), [TIMP-2]•[IGFBP7], is clinically available in many parts of the world, including the USA and Europe. We sought to understand how the test is currently being used clinically.

Methods

We invited a group of experts knowledgeable on the utility of this test for kidney injury to a panel discussion regarding the appropriate use of the test. Specifically, we wanted to identify which patients would be appropriate for testing, how the results are interpreted, and what actions would be taken based on the results of the test. We used a modified Delphi method to prioritize specific populations for testing and actions based on biomarker test results. No attempt was made to evaluate the evidence in support of various actions however.

Results

Our results indicate that clinical experts have developed similar practice patterns for use of the [TIMP-2]•[IGFBP7] test in Europe and North America. Patients undergoing major surgery (both cardiac and non-cardiac), those who were hemodynamically unstable, or those with sepsis appear to be priority patient populations for testing kidney stress. It was agreed that, in patients who tested positive, management of potentially nephrotoxic drugs and fluids would be a priority. Patients who tested negative may be candidates for “fast-track” protocols.

Conclusion

In the experience of our expert panel, biomarker testing has been a priority after major surgery, hemodynamic instability, or sepsis. Our panel members reported that a positive test prompts management of nephrotoxic drugs as well as fluids, while patients with negative results are considered to be excellent candidates for “fast-track” protocols.
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Literature
1.
go back to reference Kidney Disease. Improving Global Outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Inter Suppl. 2012;2(1):1–138.CrossRef Kidney Disease. Improving Global Outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Inter Suppl. 2012;2(1):1–138.CrossRef
2.
go back to reference Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, Bihorac A, Birkhahn R, Cely CM, Chawla LS, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17(1):R25.CrossRef Kashani K, Al-Khafaji A, Ardiles T, Artigas A, Bagshaw SM, Bell M, Bihorac A, Birkhahn R, Cely CM, Chawla LS, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17(1):R25.CrossRef
3.
go back to reference NephroCheck® Test Kit Package Insert. Astute Medical, San Diego; 2014. NephroCheck® Test Kit Package Insert. ​Astute Medical, San Diego; 2014.
4.
go back to reference Pajenda S, Ilhan-Mutlu A, Preusser M, Roka S, Druml W, Wagner L. NephroCheck data compared to serum creatinine in various clinical settings. BMC Nephrol. 2015;16:206.CrossRef Pajenda S, Ilhan-Mutlu A, Preusser M, Roka S, Druml W, Wagner L. NephroCheck data compared to serum creatinine in various clinical settings. BMC Nephrol. 2015;16:206.CrossRef
5.
go back to reference Uettwiller-Geiger DL, Vijayendran R, Kellum JA, Fitzgerald RL. Analytical characteristics of a biomarker-based risk assessment test for acute kidney injury (AKI). Clin Chim Acta. 2016;455:93–8.CrossRef Uettwiller-Geiger DL, Vijayendran R, Kellum JA, Fitzgerald RL. Analytical characteristics of a biomarker-based risk assessment test for acute kidney injury (AKI). Clin Chim Acta. 2016;455:93–8.CrossRef
6.
go back to reference Gunnerson KJ, Shaw AD, Chawla LS, Bihorac A, Al-Khafaji A, Kashani K, Lissauer M, Shi J, Walker MG, Kellum JA, et al. TIMP2*IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients. J Trauma Acute Care Surg. 2016;80(2):243–9.CrossRef Gunnerson KJ, Shaw AD, Chawla LS, Bihorac A, Al-Khafaji A, Kashani K, Lissauer M, Shi J, Walker MG, Kellum JA, et al. TIMP2*IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients. J Trauma Acute Care Surg. 2016;80(2):243–9.CrossRef
7.
go back to reference Meersch M, Schmidt C, Hoffmeier A, Van Aken H, Wempe C, Gerss J, Zarbock A. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial. Intensive Care Med. 2017;43(11):1551–61.CrossRef Meersch M, Schmidt C, Hoffmeier A, Van Aken H, Wempe C, Gerss J, Zarbock A. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high risk patients identified by biomarkers: the PrevAKI randomized controlled trial. Intensive Care Med. 2017;43(11):1551–61.CrossRef
8.
go back to reference Ostermann M, McCullough PA, Forni LG, Bagshaw SM, Joannidis M, Shi J, Kashani K, Honore PM, Chawla LS, Kellum JA, et al. Kinetics of urinary cell cycle arrest markers for acute kidney injury following exposure to potential renal insults. Crit Care Med. 2018;46(3):375–83.CrossRef Ostermann M, McCullough PA, Forni LG, Bagshaw SM, Joannidis M, Shi J, Kashani K, Honore PM, Chawla LS, Kellum JA, et al. Kinetics of urinary cell cycle arrest markers for acute kidney injury following exposure to potential renal insults. Crit Care Med. 2018;46(3):375–83.CrossRef
10.
go back to reference McIlroy DR, Argenziano M, Farkas D, Umann T, Sladen RN. Incorporating oliguria into the diagnostic criteria for acute kidney injury after on-pump cardiac surgery: impact on incidence and outcomes. J Cardiothorac Vasc Anesth. 2013;27(6):1145–52.CrossRef McIlroy DR, Argenziano M, Farkas D, Umann T, Sladen RN. Incorporating oliguria into the diagnostic criteria for acute kidney injury after on-pump cardiac surgery: impact on incidence and outcomes. J Cardiothorac Vasc Anesth. 2013;27(6):1145–52.CrossRef
11.
go back to reference Gocze I, Jauch D, Gotz M, Kennedy P, Jung B, Zeman F, Gnewuch C, Graf BM, Gnann W, Banas B, et al. Biomarker-guided intervention to prevent acute kidney injury after major surgery: the prospective randomized BigpAK study. Ann Surg. 2018;267(6):1013–20.CrossRef Gocze I, Jauch D, Gotz M, Kennedy P, Jung B, Zeman F, Gnewuch C, Graf BM, Gnann W, Banas B, et al. Biomarker-guided intervention to prevent acute kidney injury after major surgery: the prospective randomized BigpAK study. Ann Surg. 2018;267(6):1013–20.CrossRef
12.
go back to reference Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411–23.CrossRef Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG, Gomersall CD, Govil D, et al. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411–23.CrossRef
13.
go back to reference Kellum JA, Chawla LS, Keener C, Singbartl K, Palevsky PM, Pike FL, Yealy DM, Huang DT, Angus DC, ProCess, et al. The effects of alternative resuscitation strategies on acute kidney injury in patients with septic shock. Am J Respir Crit Care Med. 2016;193(3):281–7.CrossRef Kellum JA, Chawla LS, Keener C, Singbartl K, Palevsky PM, Pike FL, Yealy DM, Huang DT, Angus DC, ProCess, et al. The effects of alternative resuscitation strategies on acute kidney injury in patients with septic shock. Am J Respir Crit Care Med. 2016;193(3):281–7.CrossRef
14.
go back to reference Meersch M, Schmidt C, Van Aken H, Martens S, Rossaint J, Singbartl K, Gorlich D, Kellum JA, Zarbock A. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One. 2014;9(3):e93460.CrossRef Meersch M, Schmidt C, Van Aken H, Martens S, Rossaint J, Singbartl K, Gorlich D, Kellum JA, Zarbock A. Urinary TIMP-2 and IGFBP7 as early biomarkers of acute kidney injury and renal recovery following cardiac surgery. PLoS One. 2014;9(3):e93460.CrossRef
15.
go back to reference Pilarczyk K, Edayadiyil-Dudasova M, Wendt D, Demircioglu E, Benedik J, Dohle DS, Jakob H, Dusse F. Urinary [TIMP-2]*[IGFBP7] for early prediction of acute kidney injury after coronary artery bypass surgery. Ann Intensive Care. 2015;5(1):50.CrossRef Pilarczyk K, Edayadiyil-Dudasova M, Wendt D, Demircioglu E, Benedik J, Dohle DS, Jakob H, Dusse F. Urinary [TIMP-2]*[IGFBP7] for early prediction of acute kidney injury after coronary artery bypass surgery. Ann Intensive Care. 2015;5(1):50.CrossRef
16.
go back to reference Wang Y, Zou Z, Jin J, Teng J, Xu J, Shen B, Jiang W, Zhuang Y, Liu L, Luo Z, et al. Urinary TIMP-2 and IGFBP7 for the prediction of acute kidney injury following cardiac surgery. BMC Nephrol. 2017;18(1):177.CrossRef Wang Y, Zou Z, Jin J, Teng J, Xu J, Shen B, Jiang W, Zhuang Y, Liu L, Luo Z, et al. Urinary TIMP-2 and IGFBP7 for the prediction of acute kidney injury following cardiac surgery. BMC Nephrol. 2017;18(1):177.CrossRef
17.
go back to reference Wetz AJ, Richardt EM, Wand S, Kunze N, Schotola H, Quintel M, Brauer A, Moerer O. Quantification of urinary TIMP-2 and IGFBP-7: an adequate diagnostic test to predict acute kidney injury after cardiac surgery? Critical Care. 2015;19:3.CrossRef Wetz AJ, Richardt EM, Wand S, Kunze N, Schotola H, Quintel M, Brauer A, Moerer O. Quantification of urinary TIMP-2 and IGFBP-7: an adequate diagnostic test to predict acute kidney injury after cardiac surgery? Critical Care. 2015;19:3.CrossRef
18.
go back to reference Cummings JJ, Shaw AD, Shi J, Lopez MG, O'Neal JB, Billings FT. Intraoperative prediction of cardiac surgery-associated acute kidney injury using urinary biomarkers of cell cycle arrest. J Thorac Cardiovasc Surg. 2019;157(4):1545-53.e5CrossRef Cummings JJ, Shaw AD, Shi J, Lopez MG, O'Neal JB, Billings FT. Intraoperative prediction of cardiac surgery-associated acute kidney injury using urinary biomarkers of cell cycle arrest. J Thorac Cardiovasc Surg. 2019;157(4):1545-53.e5CrossRef
19.
go back to reference Fiorentino M, Keener CM, Smith A, Kellum JA. Cell-cycle arrest biomarkers TIMP2*IGFBP7 predict worse outcomes in septic patients without clinical evidence of AKI. J Am Soc Nephrol. 2017;28:Abstarct Suppl p27. Fiorentino M, Keener CM, Smith A, Kellum JA. Cell-cycle arrest biomarkers TIMP2*IGFBP7 predict worse outcomes in septic patients without clinical evidence of AKI. J Am Soc Nephrol. 2017;28:Abstarct Suppl p27.
20.
go back to reference Luther MK, Timbrook TT, Caffrey AR, Dosa D, Lodise TP, LaPlante KL. Vancomycin plus piperacillin-tazobactam and acute kidney injury in adults: a systematic review and meta-analysis. Crit Care Med. 2018;46(1):12–20.CrossRef Luther MK, Timbrook TT, Caffrey AR, Dosa D, Lodise TP, LaPlante KL. Vancomycin plus piperacillin-tazobactam and acute kidney injury in adults: a systematic review and meta-analysis. Crit Care Med. 2018;46(1):12–20.CrossRef
21.
go back to reference Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA. Costs and outcomes of acute kidney injury (AKI) following cardiac surgery. Nephrol Dial Transplant. 2008;23(6):1970–4.CrossRef Dasta JF, Kane-Gill SL, Durtschi AJ, Pathak DS, Kellum JA. Costs and outcomes of acute kidney injury (AKI) following cardiac surgery. Nephrol Dial Transplant. 2008;23(6):1970–4.CrossRef
22.
go back to reference Alshaikh HN, Katz NM, Gani F, Nagarajan N, Canner JK, Kacker S, Najjar PA, Higgins RS, Schneider EB. Financial impact of acute kidney injury after cardiac operations in the United States. Ann Thorac Surg. 2018;105(2):469–75.CrossRef Alshaikh HN, Katz NM, Gani F, Nagarajan N, Canner JK, Kacker S, Najjar PA, Higgins RS, Schneider EB. Financial impact of acute kidney injury after cardiac operations in the United States. Ann Thorac Surg. 2018;105(2):469–75.CrossRef
23.
go back to reference Su LJ, Li YM, Kellum JA, Peng ZY. Predictive value of cell cycle arrest biomarkers for cardiac surgery-associated acute kidney injury: a meta-analysis. Br J Anaesth. 2018;121(2):350–7.CrossRef Su LJ, Li YM, Kellum JA, Peng ZY. Predictive value of cell cycle arrest biomarkers for cardiac surgery-associated acute kidney injury: a meta-analysis. Br J Anaesth. 2018;121(2):350–7.CrossRef
24.
go back to reference Liu C, Lu X, Mao Z, Kang H, Liu H, Pan L, Hu J, Wang L, Zhou F. The diagnostic accuracy of urinary [TIMP-2].[IGFBP7] for acute kidney injury in adults: a PRISMA-compliant meta-analysis. Medicine. 2017;96(27):e7484.CrossRef Liu C, Lu X, Mao Z, Kang H, Liu H, Pan L, Hu J, Wang L, Zhou F. The diagnostic accuracy of urinary [TIMP-2].[IGFBP7] for acute kidney injury in adults: a PRISMA-compliant meta-analysis. Medicine. 2017;96(27):e7484.CrossRef
25.
go back to reference Jia HM, Huang LF, Zheng Y, Li WX. Prognostic value of cell cycle arrest biomarkers in patients at high risk for acute kidney injury: a systematic review and meta-analysis. Nephrology (Carlton). 2017;22(11):831–7.CrossRef Jia HM, Huang LF, Zheng Y, Li WX. Prognostic value of cell cycle arrest biomarkers in patients at high risk for acute kidney injury: a systematic review and meta-analysis. Nephrology (Carlton). 2017;22(11):831–7.CrossRef
26.
go back to reference Jia HM, Huang LF, Zheng Y, Li WX. Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis. Critical Care. 2017;21(1):77.CrossRef Jia HM, Huang LF, Zheng Y, Li WX. Diagnostic value of urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 for acute kidney injury: a meta-analysis. Critical Care. 2017;21(1):77.CrossRef
27.
go back to reference Su Y, Gong Z, Wu Y, Tian Y, Liao X. Diagnostic value of urine tissue inhibitor of Metalloproteinase-2 and insulin-like growth factor-binding protein 7 for acute kidney injury: a meta-analysis. PLoS One. 2017;12(1):e0170214.CrossRef Su Y, Gong Z, Wu Y, Tian Y, Liao X. Diagnostic value of urine tissue inhibitor of Metalloproteinase-2 and insulin-like growth factor-binding protein 7 for acute kidney injury: a meta-analysis. PLoS One. 2017;12(1):e0170214.CrossRef
Metadata
Title
Clinical use of [TIMP-2]•[IGFBP7] biomarker testing to assess risk of acute kidney injury in critical care: guidance from an expert panel
Authors
Louis M. Guzzi
Tobias Bergler
Brian Binnall
Daniel T. Engelman
Lui Forni
Michael J. Germain
Eric Gluck
Ivan Göcze
Michael Joannidis
Jay L. Koyner
V. Seenu Reddy
Thomas Rimmelé
Claudio Ronco
Julien Textoris
Alexander Zarbock
John A. Kellum
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2019
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-019-2504-8

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