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

Tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are postoperative urinary biomarkers of renal stress and acute kidney injury (AKI). We conducted this study to test the hypothesis that intraoperative concentrations of urinary [TIMP-2]·[IGFBP...

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Vydáno v:The Journal of thoracic and cardiovascular surgery Ročník 157; číslo 4; s. 1545
Hlavní autoři: Cummings, Jared J, Shaw, Andrew D, Shi, Jing, Lopez, Marcos G, O'Neal, Jason B, Billings, 4th, Frederic T
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.04.2019
Témata:
Acute Kidney Injury - diagnosis
Acute Kidney Injury - etiology
Acute Kidney Injury - urine
Aged
Biomarkers - urine
Cardiac Surgical Procedures - adverse effects
Cell Cycle Checkpoints
Female
Humans
Insulin-Like Growth Factor Binding Proteins - urine
Intraoperative Period
Male
Middle Aged
Predictive Value of Tests
Prospective Studies
Randomized Controlled Trials as Topic
Risk Assessment
Risk Factors
Time Factors
Tissue Inhibitor of Metalloproteinase-2 - urine
Treatment Outcome
Up-Regulation
Urinalysis
cardiac surgery
TIMP-2
IGFBP7
acute kidney injury
biomarker
NephroCheck, prediction
ISSN:1097-685X, 1097-685X
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Shrnutí:Tissue inhibitor of metalloproteinases 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are postoperative urinary biomarkers of renal stress and acute kidney injury (AKI). We conducted this study to test the hypothesis that intraoperative concentrations of urinary [TIMP-2]·[IGFBP7] are associated with postoperative AKI. We measured urinary [TIMP-2]·[IGFBP7] at 8 perioperative timepoints in 400 patients who participated in a randomized controlled trial of atorvastatin for AKI in cardiac surgery. We compared [TIMP-2]·[IGFBP7] between subjects who did and did not develop KDIGO stage 2 or 3 AKI within 48 hours of surgery, adjusted for AKI risk factors. Fourteen patients (3.5%) met the primary endpoint of stage 2 or 3 AKI within 48 hours of surgery, and an additional 77 patients (19.3%) developed stage 1 AKI. Patients who developed stage 2 or 3 AKI displayed bimodal elevations of [TIMP-2]·[IGFBP7], with a first elevation (median, 0.45 [ng/mL] /1000) intraoperatively and a second elevation (1.45 [ng/mL] /1000) 6 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 or 3 AKI (P = .01), and each 10-fold increase in the 6 hours postoperative [TIMP-2]·[IGFBP7] was independently associated with a 650% increase in the odds of stage 2 or 3 AKI (P < .001). The maximum [TIMP-2]·[IGFBP7] between these 2 timepoints provided an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI], 0.73-0.90), 100% sensitivity, and 100% negative predictive value using the >0.3 cutoff to predict stage 2 or 3 AKI. Intraoperative elevations of [TIMP-2]·[IGFBP7] can predict moderate or severe AKI and could provide an opportunity to alter postoperative management to prevent kidney injury.
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ISSN:1097-685X
1097-685X
DOI:10.1016/j.jtcvs.2018.08.090