TIMP-2/IGFBP7 predicts acute kidney injury in out-of-hospital cardiac arrest survivors.

Background: Acute kidney injury (AKI) is a common complication after cardiopulmonary resuscitation (CPR) and predicts in-hospital mortality. To which extent post-resuscitation disease or the initial event of cardiac arrest and the duration of insufficient cardiac output triggers AKI is challenging to discriminate. Knowledge on molecular mediators of AKI is scarce. Early identification of patients at high risk of AKI is hampered by the low sensitivity of the established tests in clinical routine practice. The present study aimed to determine the diagnostic utility of the novel urine biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) for the early recognition of AKI in patients with non-traumatic shock.

Methods: The performance of [TIMP-2]·[IGFBP7] was prospectively analysed in 48 patients with shock following out-of-hospital cardiac arrest (OHCA). All patients were treated with target temperature management (TTM) for 24 h. Urinary [TIMP-2]·[IGFBP7] samples were collected at 3 and 24 h after determination of OHCA.

Results: Patients (n = 31 (65%)) developed AKI after an average of 26 ± 12 h. Patients who developed AKI had significantly higher [TIMP-2]·[IGFBP7] compared to individuals that did not develop AKI (1.52 ± 0.13 vs. 0.13 ± 0.14; p < 0.05) as early as 3 h after determination of OHCA,. For urine [TIMP-2]*[IGFBP7], the area under the curve (AUC) for the development of AKI was 0.97 (CI 0.90-1.00) at 3 h after OHCA. The optimal [TIMP-2]·[IGFBP7] cut-off value for the prediction of AKI was 0.24. The sensitivity was 96.8% and specificity was 94.1%.

Conclusions: Urinary [TIMP-2]•[IGFBP7] reliably predicts AKI in high-risk patients only 3 h after determination of OHCA with a cut-off at 0.24. This novel test may help to identify patients at high risk of AKI to enrol into clinical studies to further elucidate the pathophysiology of AKI and devise targeted interventions in the future.