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

Abstract

Background: Acute 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.

Methods: Adult 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.

Results: We 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.

Conclusion: The 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.

Keywords: Acute kidney injury; Biomarker; Cardiac surgery; IGFBP7; TIMP-2.

Fig. 1

ROC curves for prediction of AKI using [TIMP-2]•[IGFBP7] results from urine samples collected 4 h after ICU admission. a prediction for all AKI, AUC = 0.80 (95% confidence interval 0.68 to 0.91, b prediction for stage 2–3 AKI, AUC = 0.83 (95% CI 0.69 to 0.96). AKI acute kidney injury, AUC the area under the ROC curve

Fig. 2

Mean [TIMP-2]•[IGFBP7] values in patients who developed AKI and those who did not. Times post-surgery are relative to ICU admission. Error bars show standard error. *p < 0.05, **p < 0.001