Usefulness of the Biomarker TIMP-2•IGFBP7 for Acute Kidney Injury Assessment in Critically Ill Patients: A Narrative Review

Abstract

Objectives: To review the clinical usefulness of the biomarker TIMP-2•IGFBP7 in adult, general medical-surgical intensive care unit (ICU) settings. Data Sources: PubMed (1946 to mid-February 2021) and EMBASE (1947 to mid-February 2021) with bibliographies of retrieved articles reviewed for additional articles. Study Selection and Data Extraction: Studies evaluating use of the urinary TIMP-2•IGFBP7 assay in adult patients in ICU settings. Data Synthesis: Studies published after investigations leading to TIMP-2•IGFBP7 assay approval confirm the appropriateness of considerations discussed in product labeling, such as use of the test within 12 hours of assessment, use of a dichotomous 0.3 (ng/mL)2/1000 cutoff, and use only in combination with other assessments of acute kidney injury (AKI). However, as a biomarker routinely used for early identification of patients at risk for AKI in mixed ICU populations, the additional resources required for TIMP-2•IGFBP monitoring are difficult to justify because of limited data demonstrating usefulness in preventing or ameliorating AKI and its attendant complications. Relevance to Patient Care and Clinical Practice: Biomarkers are potentially useful not only for assessment and diagnosis of AKI, but also for practitioners involved in the management of nephrotoxic medications and medications needing adjustment for decreased kidney function. Conclusions: Although there is evidence to suggest that the urinary TIMP-2•IGFBP7 biomarker is helpful in predicting AKI progression in general medical-surgical ICU patients when used within 12 hours of patient assessment in combination with routine testing, including serum creatinine and urine output, there is little evidence that its use leads to improvements in clinically important patient outcomes.

Moving toward a contemporary classification of drug-induced kidney disease

“…Besides these two biomarkers, urinary IL-18, L-FABP, and TIMP-2•IGFBP7 can also help diagnose ATI early and differentiate injury from dysfunction. Urinary TIMP-2•IGFBP7 appears to be an appropriate candidate damage biomarker of DIKD, particularly in preoperative and critically ill settings, because of its features discussed elsewhere [43,44]. Three novel functional biomarkers in serum have been introduced and studied in clinical settings.…”

Nephrology Considerations in the Management of Durable and Temporary Mechanical Circulatory Support

“…Direct information about kidney parenchymal injury in the preimplantation period could be provided by an approved kidney biomarker score calculated from urinary concentrations of the cell cycle arrest markers insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), although this biomarker score has not been validated in this setting. 36…”

“…Data about parenchymal kidney health and reserve can be obtained from a detailed history, including long-term eGFR and albuminuria trends, prior AKI episodes, review of any prior kidney procedures (e.g., lithotripsy, partial nephrectomy), urinalysis and sediment examination, and evaluation of the preimplantation period (trends in urine output and endogenous filtration markers, systemic perfusion). Direct information about kidney parenchymal injury in the preimplantation period could be provided by an approved kidney biomarker score calculated from urinary concentrations of the cell-cycle arrest markers insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP2), although this biomarker score has not been validated in this setting (36).…”