Urinary TIMP-2 and IGFBP7 as Early Biomarkers of Acute Kidney Injury and Renal Recovery following Cardiac Surgery

Abstract

BackgroundDifficulties in prediction and early identification of (acute kidney injury) AKI have hindered the ability to develop preventive and therapeutic measures for this syndrome. We tested the hypothesis that a urine test measuring insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in acute kidney injury (AKI), could predict AKI in cardiac surgery patients.MethodsWe studied 50 patients at high risk for AKI undergoing cardiac surgery with cardiopulmonary bypass (CPB). Serial urine samples were analyzed for [TIMP-2]*[IGFBP7] concentrations. The primary outcome measure was AKI as defined by international consensus criteria following surgery. Furthermore, we investigated whether urine [TIMP-2]*[IGFBP7] could predict renal recovery from AKI prior to hospital discharge.Results26 patients (52%) developed AKI. Diagnosis based on serum creatinine and/or oliguria did not occur until 1–3 days after CPB. In contrast, urine concentration of [TIMP-2]*[IGFBP7] rose from a mean of 0.49 (SE 0.24) at baseline to 1.51 (SE 0.57) 4 h after CPB in patients who developed AKI. The maximum urinary [TIMP-2]*[IGFBP7] concentration achieved in the first 24 hours following surgery (composite time point) demonstrated an area under the receiver-operating characteristic curve of 0.84. Sensitivity was 0.92, and specificity was 0.81 for a cutoff value of 0.50. The decline in urinary [TIMP-2]*[IGFBP7] values was the strongest predictor for renal recovery.ConclusionsUrinary [TIMP-2]*[IGFBP7] serves as a sensitive and specific biomarker to predict AKI early after cardiac surgery and to predict renal recovery.Clinical Trial Registration Information: www.germanctr.de/, DRKS-ID: DRKS00005062

ABT‐719 for the Prevention of Acute Kidney Injury in Patients Undergoing High‐Risk Cardiac Surgery: A Randomized Phase 2b Clinical Trial

“…Biomarkers of AKI, such as NGAL, KIM‐1, and IL‐18, may be potentially beneficial for early detection, diagnosis, and prognosis of AKI after cardiac surgery 35, 36. However, in our study and others, these markers are commonly elevated at baseline, and thus a relatively large change from baseline (doubling or tripling) would be needed to detect AKI in this setting 37, 38, 39.…”

Septic acute kidney injury in critically ill patients – a single-center study on its incidence, clinical characteristics, and outcome predictors

“…23 His hypothesis is supported by recent clinical studies, which demonstrated that two G1 cell cycle arrest markers, namely, insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase 2 (TIMP-2), predicted AKI in critically ill, and cardiac surgical patients. [24][25][26] This adaptive response may be controlled by mitochondria, with the aim to limit further cellular damage and provide cells with the opportunity to recover function. 27 By shutting down some non-essential cellular functions, remaining energy can be directed to other functions that are required for cell survival.…”

Urine biomarkers in renal allograft

“…The major function of this protein is to regulate the availability of insulin-like growth factors (IGFs) in tissue as well as in modulating IGF binding to its receptors. The combination of urinary TIMP-2 and IGFBP7 serves as a sensitive and specific biomarker to predict AKI early after cardiac surgery and to predict renal recovery [17] . Urinary TIMP-2 and IGFBP7 were identified as patients at risk for imminent AKI [18] .…”

“…Combination of urinary TIMP-2 and urinary IGFBP7 may be important for clinical adjudication of AKI and risk of kidney failure Identified patients at risk for imminent AKI based on levels of urinary [TIMP-2] * [IGFBP7] [18] Kathleen D. Liu [32] ; Melanie Meersch [17] …”