Clinical Use of the Urine Biomarker [TIMP-2] × [IGFBP7] for Acute Kidney Injury Risk Assessment

Anitha Vijayan, Sarah Faubel, David J Askenazi, Jorge Cerda, William H Fissell, Michael Heung, Benjamin D Humphreys, Jay L Koyner, Kathleen D Liu, Girish Mour, Thomas D Nolin, Azra Bihorac, American Society of Nephrology Acute Kidney Injury Advisory Group, Sarah Faubel, David J Askenazi, Rajit K Basu, Udayan Y Bhatt, Azra Bihorac, Jorge Cerda, Michael J Connor Jr, Alan J Davidson, Mark P de Caestecker, Kent Doi, William H Fissell, Ladan Golestaneh, Michael Heung, Benjamin D Humphreys, Jay L Koyner, Kathleen D Liu, Girish K Mour, Prabhleen Singh, Charuhas V Thakar, Anitha Vijayan, Anitha Vijayan, Sarah Faubel, David J Askenazi, Jorge Cerda, William H Fissell, Michael Heung, Benjamin D Humphreys, Jay L Koyner, Kathleen D Liu, Girish Mour, Thomas D Nolin, Azra Bihorac, American Society of Nephrology Acute Kidney Injury Advisory Group, Sarah Faubel, David J Askenazi, Rajit K Basu, Udayan Y Bhatt, Azra Bihorac, Jorge Cerda, Michael J Connor Jr, Alan J Davidson, Mark P de Caestecker, Kent Doi, William H Fissell, Ladan Golestaneh, Michael Heung, Benjamin D Humphreys, Jay L Koyner, Kathleen D Liu, Girish K Mour, Prabhleen Singh, Charuhas V Thakar, Anitha Vijayan

Abstract

Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 ([TIMP-2] × [IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI.

Keywords: Acute kidney injury (AKI); NephroCheck; [TIMP-2] × [IGFBP7]; biomarker; critically ill; decreased kidney function; diagnosis; early detection; insulin-like growth factor binding protein 7; renal dysfunction; risk assessment; tissue inhibitor of metalloproteinase 2.

Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
Hypothetical clinical scenario showing a potential use for [TIMP-2]x[IGFBP7] in a critically ill patient. ICU: intensive care unit; Scr; serum creatinine; AKI: acute kidney injury; FENa: fractional excretion of sodium; FEurea: fractional excretion of urea; ACEi: angiotensin converting enzyme inhibitor; ARB: angiotensin receptor blocker; NSAIDs: non-steroidal anti-inflammatory drugs. Note: The authors have presented this hypothetical case illustration to demonstrate a possible use for this biomarker. To date, this algorithm has not been standardized and is not in use at any of medical centers that is affiliated with the authors. We recommend that each center institute its own protocol to ensure the appropriate use of this test.

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