Urinary TIMP-2 and IGFBP7 for the prediction of acute kidney injury following cardiac surgery

Abstract

BackgroundAcute kidney injury (AKI) following cardiac surgery is common and associated with poor patient outcomes. Early risk assessment for development of AKI remains a challenge. The combination of urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) has been shown to be an excellent predictor of AKI following cardiac surgery, but reported studies are for predominately non-Asian populations.MethodsAdult patients were prospectively enrolled at Zhongshan hospital in Shanghai, China. The primary analysis was prediction of AKI and stage 2–3 AKI by [TIMP-2]*[IGFBP7] measured 4 h after postoperative ICU admission assessed using receiver operating characteristic curve (ROC) analysis. Kinetics of [TIMP-2]*[IGFBP7] following ICU admission were also examined.ResultsWe prospectively enrolled 57 cardiac surgery patients, of which 20 (35%) developed AKI and 6 (11%) developed stage 2–3 AKI. The area under the ROC curve (AUC) of [TIMP-2]*[IGFBP7] at 4 h after ICU admission was 0.80 (95% confidence interval (CI): 0.68–0.91) for development of AKI and 0.83 (95% CI: 0.69–0.96) for development of stage 2–3 AKI. Urinary [TIMP-2]*[IGFBP7] values at 4 h after ICU admission were significantly (P < 0.001) higher in patients who developed AKI than in patients who did not develop AKI (mean (standard error) of 1.08 (0.34) (ng/mL)2/1000 and 0.29 (0.05) (ng/mL)2/1000, respectively). The time-profile of [TIMP-2]*[IGFBP7] suggests the markers started to elevate by the time of ICU admission in patients who developed AKI and either decreased or remained flat in patients without AKI.ConclusionThe combination of urinary TIMP-2 and IGFBP7 4 h after postoperative ICU admission identifies patients at risk for developing AKI, not just stage 2–3 AKI following cardiac surgery.

Intraoperative prediction of cardiac surgery–associated acute kidney injury using urinary biomarkers of cell cycle arrest

“…28 18 This 0.3 cutoff was further validated in another cohort of ICU patients and also among adults undergoing cardiac surgery. 14,15,27,29,30 15 If neither the intraoperative nor the early postoperative test is positive (>0.3), the treating clinician may be confident the patients will not develop moderate-severe AKI (the "double-negative" [TIMP-2]•[IGFBP7]). Indeed, the negative predictive value using this sampling strategy in the current study was 100%.…”

Risk Factors for Acute Kidney Injury in Hospitalized Non–Critically Ill Patients: A Population-Based Study

“…Thus, models developed in a cardiac surgery cohort may not work well in general ward patients. 36,37 Critically ill patients have higher AKI event rates than do non-ICU patients and also have unique risk factors. These factors can all affect the performance of any model developed in an ICU setting if applied to general ward patients.…”

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

“…Studies have reported a variety of results in this regard. In several studies [14–16], [TIMP-2]•[IGFBP7] detected elevations at 4 h; in another study, elevations were not detected until the day after surgery [17]. A recent study [18], with the most granular time-course published to date, shows bimodal elevations of [TIMP-2]•[IGFBP7] with the first peak occurring intraoperatively and the second 6 h after ICU admission in patients who developed stages 2/3 AKI.…”