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Kinetics of urinary cell cycle arrest markers for acute kidney injury following exposure to potential renal insults

Journal Contribution - Journal Article

Objectives: Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 predict the development of acute kidney injury following renal insults of varied aetiology. To aid clinical interpretation, we describe the kinetics of biomarker elevations around an exposure. Design: In an ancillary analysis of the multicenter SAPPHIRE study, we examined the kinetics of the urinary [tissue inhibitor of metalloproteinase-2]center dot[insulin-like growth factor binding protein 7] in association with exposure to common renal insults (major surgery, IV radiocontrast, vancomycin, nonsteroidal anti-inflammatory drugs, and piperacillin/tazobactam). Setting: Thirty-five sites in North America and Europe between September 2010 and June 2012. Patients: Seven hundred twenty-three critically ill adult patients admitted to the ICU. Interventions: None. Measurements and Main Results: We compared the urinary [tissue metalloproteinase-2]center dot[insulin growth factor binding protein 7] kinetics from the day prior to exposure up to 5 days after exposure in patients developing acute kidney injury stage 2-3, stage 1, or no acute kidney injury by Kidney Disease Improving Global Outcome criteria. Among the 723 patients, 679 (94%) had at least one, 70% had more than one, and 35% had three or more exposures to a known renal insult. There was a significant association between cumulative number of exposures up to study day 3 and risk of acute kidney injury (p = 0.02) but no association between the specific type of exposure and acute kidney injury (p = 0.22). With the exception of radiocontrast, patients who developed acute kidney injury stage 2-3 after one of the five exposures, had a clear rise and fall of urinary [tissue inhibitor of metalloproteinase-2]center dot[insulin-like growth factor binding protein 7] from the day of exposure to 24-48 hours later. In patients without acute kidney injury, there was no significant elevation in urinary [tissue inhibitor of metalloproteinase-2]center dot[insulin-like growth factor binding protein 7]. Conclusions: Exposure to potential renal insults is common. In patients developing acute kidney injury stage 2-3, the kinetics of urinary [tissue inhibitor of metalloproteinase-2]center dot[insulin-like growth factor binding protein 7] matched the exposure except in the case of radiocontrast.
Journal: Critical Care Medicine
ISSN: 0090-3493
Issue: 3
Volume: 46
Pages: 375 - 383
Publication year:2018