Urinary [TIMP-2]*[IGFBP7] for early prediction of acute kidney injury after coronary artery bypass surgery

Abstract

BackgroundAcute kidney injury (AKI) is a common complication after cardiac surgery. Currently, prediction of AKI with classical tools remains uncertain. Therefore, it was the aim of the present study to evaluate two new urinary biomarkers—insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in patients after coronary artery bypass surgery (CABG).MethodsIn a prospective cohort study, 60 consecutive patients undergoing isolated on-pump CABG were enrolled. Urine samples collected every 12 h in the postoperative course were analyzed for the product of TIMP-2 and IGFBP7. Urinary output, serum creatinine and estimated glomerular filtration rate (eGFR) were recorded simultaneously. Primary clinical endpoint was the development of AKI stage 2 or 3 according to the classification of the KDIGO within 48 h after surgery.Results48 male and 12 female patients with a mean age of 69.61 ± 8.4 years were included. 19 patients developed an AKI (31.6 %), six patients met the endpoint with AKI 2 or 3 (10 %). Urinary [TIMP-2]*[IGFBP7] increased significantly as early as 4 h after CABG in patients with AKI 2/3 (1.83 ± 2.15 vs. 0.23 ± 0.45, p < 0.05) whereas serum creatinine did not increase until 48 h after surgery. The diagnostic accuracy of [TIMP 2]*[IGFBP7] on day one after surgery for the prediction of AKI 2/3 was significantly better (sensitivity 0.89, specificity 0.81, AUC 0.817, 95 % CI 0.622–1.0 SE 0.099, p = 0.022, cut-off 0.817) than for serum creatinine (AUC 0.359, sensitivity 0.50, specificity of 0.52, cut-off value 1.17 mg/dl) and eGFR.ConclusionUrinary [TIMP-2]*[IGFBP7] represents a sensitive and specific biomarker to predict moderate to severe AKI very early after CABG. Analyses from our ongoing larger study are necessary to confirm these findings and probably increase sensitivity and specificity.

TIMP-2*IGFBP7 (Nephrocheck®) Measurements at Intensive Care Unit Admission After Cardiac Surgery are Predictive for Acute Kidney Injury Within 48 Hours

“…The dynamics seem to be dependent on the cause, severity as well as the recovery of AKI [7, 17]. After CABG surgery, measurement of [TIMP-2*IGFBP7] predicted AKI in smaller cohorts [16-18]. Wetz et al could not demonstrate any association of early [TIMP-2*IGFBP7] measurements and postoperative AKI [18].…”

“…Recent publications indicate that this method can detect AKI endangered patients in a very early state [7, 12-15]. Yet, it is unknown at which time-point [TIMP-2*IGFBP7] (Nephrocheck®) measurement should be performed to predict AKI in patients undergoing cardiac surgery [16-18]. …”

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…Further investigations will be needed to establish this association with HFpEF. Urinary IGFBP-7 levels are, together with tissue inhibitor of metalloproteinase 2 (TIMP-2), predictive for acute kidney injury in decompensated HF and post-coronary artery bypass surgery [92][93][94][95]. Thus, in addition to being a plasma biomarker, levels in other body fluids such as urine can provide diagnostic and/or prognostic information about patients.…”

Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption

“…ICU [32] [ ICU [33] May be elevated in the setting of diabetes [34] 0.82 ICU [35] 0.79 ICU [36] 0.84 Cardiac surgery [37] 0.82 Coronary artery bypass surgery [38] 0.71 Coronary artery bypass surgery [39] 0.84 High-risk surgical patients [40] 0.85 Major surgery [41] Calprotectin A 24-kDa heterodimer composed of the 2 monomers S100A8 (10,835 Da) and S100A9 (13,242 Da); promotion of repair after AKI 0.97 Hospitalized patients [42] Hospitalized patients [44] Coronary care units [45] May be elevated in the settings of urinary tract infection, rheumatoid arthritis, inflammatory bowel disease, myocardial infarction, and urothelial cancer [10,42,43] 0.99…”