Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice

Clin Chem Lab Med. 2019 Apr 24;57(5):567-576. doi: 10.1515/cclm-2018-0776.

Abstract

NephroCheck® is the commercial name of a combined product of two urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), expressed as [TIMP-2]·[IGFBP7], used to identify patients at high risk of acute kidney injury (AKI). AKI is a common and harmful complication especially in critically-ill patients, which can induce devastating short- and long-term outcomes. Over the past decade, numerous clinical studies have evaluated the utility of several biomarkers (e.g. neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein and kidney injury molecule-1, cystatin C) in the early diagnosis and risk stratification of AKI. Among all these biomarkers, [TIMP-2]·[IGFBP7] was confirmed to be superior in early detection of AKI, before the decrease of renal function is evident. In 2014, the US Food and Drug Administration permitted marketing of NephroCheck® (Astute Medical) (measuring urinary [TIMP-2]·[IGFBP7]) to determine if certain critically-ill patients are at risk of developing moderate to severe AKI. It has since been applied to clinical work in many hospitals of the United States and Europe to improve the diagnostic accuracy and outcomes of AKI patients. Now, more and more research is devoted to the evaluation of its application value, meaning and method in different clinical settings. In this review, we summarize the current research status of [TIMP-2]·[IGFBP7] and point out its future directions.

Keywords: NephroCheck®; acute kidney injury (AKI); biomarker; cell cycle arrest; insulin-like growth factor-binding protein 7 (IGFBP7); tissue inhibitor of metalloproteinases-2 (TIMP-2).

Publication types

  • Review

MeSH terms

  • Acute Kidney Injury / diagnosis*
  • Acute Kidney Injury / etiology
  • Biomarkers / urine
  • Cell Cycle Checkpoints / physiology
  • Humans
  • Insulin-Like Growth Factor Binding Proteins / urine*
  • Tissue Inhibitor of Metalloproteinase-2 / urine*

Substances

  • Biomarkers
  • Insulin-Like Growth Factor Binding Proteins
  • TIMP2 protein, human
  • insulin-like growth factor binding protein-related protein 1
  • Tissue Inhibitor of Metalloproteinase-2