• Yun Xie, Ghada Ankawi, Bo Yang, Francesco Garzotto, Alberto Passannante, Andrea Breglia, Kumar Digvijay, Fiorenza Ferrari, Alessandra Brendolan, Bonato Raffaele, Davide Giavarina, Dario Gregori, and Claudio Ronco.
• Department of Nephrology, Xin Hua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China; International Renal Research Institute of Vicenza (IRRIV), San Bortolo Hospital, Vicenza, Italy. Electronic address: xieyun@xinhuamed.com.cn.
• Kidney Int. 2019 Jun 1; 95 (6): 1486-1493.

AbstractThe G1 cell cycle inhibitors tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as novel biomarkers for the prediction of moderate to severe acute kidney injury (AKI) risk. However, the prognostic value of [TIMP-2]•[IGFBP7] in predicting adverse outcomes in intensive care unit (ICU) patients with AKI was not previously described. To evaluate this, we conducted a cohort study, measuring [TIMP2]•[IGFBP7] levels in critically ill patients admitted to the ICU and classified the patients as NephroCheck (NC) (+) or NC (-) according to [TIMP-2]•[IGFBP7] values and AKI (+) or AKI (-) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We then evaluated the incidence of continuous renal replacement therapy initiation, all-cause mortality and a composite endpoint of both in the four groups. Baseline [TIMP-2]•[IGFBP7] values were available for 719 patients, of whom 239 developed AKI and 151 met the composite endpoint. Compared to NC (-)/AKI (+) patients, NC (+)/AKI (+) patients had a significant risk of ICU mortality and the composite endpoint. Kaplan-Meier curves showed that the survival estimate for the composite endpoint of NC (+)/AKI (+) patients was 34.4%; significantly worse than NC (-)/AKI (+) patients (67.4%). Multivariate analyses showed strong association between NC positivity and the composite endpoint. The inflammatory marker, procalcitonin, was an additional prognostic biomarker to compare and confirm the incremental value of NephroCheck. No association between procalcitonin and the composite endpoint was found, especially in patients with AKI, suggesting that NephroCheck may be more kidney specific. Thus, the [TIMP-2]•[IGFBP7] values can serve to identify patients with AKI at increased risk for adverse outcomes in the ICU.Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

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