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

Abstract

Objective: Tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factorbinding protein 7 (IGFBP7) are postoperative urinary biomarkers of renal stress and AKI. We conducted this study to test the hypothesis that intraoperative concentrations of urinary [TIMP-2]•[IGFBP7] are associated with postoperative AKI. Methods: We measured urinary [TIMP-2]•[IGFBP7] at eight perioperative timepoints in 400 patients who participated in a RCT of statins for AKI in cardiac surgery. We compared [TIMP-2]•[IGFBP7] between subjects who did and did not develop KDIGO stage 2-3 AKI within 48 hours of surgery, adjusted for AKI risk factors. Results: Fourteen patients (3.5%) met the primary endpoint of stage 2-3 AKI within 48 hours of surgery, and an additional 77 patients (19.3%) developed stage 1 AKI. Patients who developed stage 2-3 AKI displayed bimodal elevations of [TIMP-2]•[IGFBP7], with a first elevation (median 0.45 [ng/mL] 2 /1000) intraoperatively and the second peak (1.45 [ng/mL] 2 /1000) six hours postoperatively. Patients who did not develop AKI did not have any elevations in [TIMP-2]•[IGFBP7]. Each 10-fold increase in intraoperative [TIMP-2]•[IGFBP7] was independently associated with a 290% increase in the odds of stage 2-3 AKI (P=0.01), and each 10-fold increase in six hours postoperative [TIMP-2]•[IGFBP7] a 650% increase (P<0.001). The maximum [TIMP-2]•[IGFBP7] between these two timepoints provided an AUROC of 0.82 (95% CI: 0.73-0.90), 100% sensitivity, and 100% negative predictive value using the >0.3 cutoff to predict stage 2-3 AKI.

<p>Evaluating Nephrocheck^® as a Predictive Tool for Acute Kidney Injury</p>

“…Urinary x [GFBP7] values > 0.3 at admission in ICU were strongly associated with the incidence of AKI 22 good sensitivity and specificity at 4 hours after CPB, and its decline at the discharge was a strong predictor for renal recovery. 19 Both intraoperative and postoperative elevations of urinary x [IGFBP-7] can predict moderate or severe AKI. 20 According to these characteristics, it is possible to increase the ability of the test to identify patients at AKI risk by the combination of urinary x [IGFBP-7] and the Renal Resistive Index (RRI) in patients scheduled for elective on-pump cardiac surgery at high risk for CSA-AKI.…”

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

“…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. The authors postulate that the first peak indicates kidney stress caused during the surgery, while the second peak may indicate kidney stress caused during early postoperative care.…”

Biomarkers of Acute Kidney Injury after Cardiac Surgery: A Narrative Review

“…Anna et al [53] agreed that [TIMP-2] x [IGFBP-7] can be used to identify patients at increased risk of AKI, but the authors also illustrated that a cutoff of 2 was not confirmed in their cohort study. Despite the various reports, a value> 0.3 seems to be acceptable [54–56]. Chiara et al [55] used the NephroCheck system to measure the urinary concentration of [TIMP-2] x [IGFBP-7] and proposed that physicians should perform therapeutic interventions when the result is >0.3 ng/dL.…”

“…Chiara et al [55] used the NephroCheck system to measure the urinary concentration of [TIMP-2] x [IGFBP-7] and proposed that physicians should perform therapeutic interventions when the result is >0.3 ng/dL. When applying the >0.3 cutoff to predict KDIGO stage 2 or 3 AKI, the AUC of 0.82 has 100% sensitivity and 100% negative predictive value [56].…”