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Licensed Unlicensed Requires Authentication Published by De Gruyter September 28, 2020

Influence of patients’ clinical features at intensive care unit admission on performance of cell cycle arrest biomarkers in predicting acute kidney injury

  • Bo Yang EMAIL logo , Yun Xie , Francesco Garzotto , Ghada Ankawi , Alberto Passannante , Alessandra Brendolan , Raffaele Bonato , Mariarosa Carta , Davide Giavarina , Enrico Vidal , Dario Gregori ORCID logo and Claudio Ronco ORCID logo



Identification of acute kidney injury (AKI) can be challenging in patients with a variety of clinical features at intensive care unit (ICU) admission, and the capacity of biomarkers in this subpopulation has been poorly studied. In our study we examined the influence that patients’ clinical features at ICU admission have over the predicting ability of the combination of urinary tissue inhibitor of metalloproteinase-2 (TIMP2) and insulin-like growth factor binding protein 7 (IGFBP7).


Urinary [TIMP2]•[IGFBP7] were measured for all patients upon admission to ICU. We calculated the receiver operating characteristics (ROC) curves for AKI prediction in the overall cohort and for subgroups of patients according to etiology of ICU admission, which included: sepsis, trauma, neurological conditions, cardiovascular diseases, respiratory diseases, and non-classifiable causes.


In the overall cohort of 719 patients, 239 (33.2%) developed AKI in the first seven days. [TIMP2]•[IGFBP7] at ICU admission were significantly higher in AKI patients than in non-AKI patients. This is true not only for the overall cohort but also in the other subgroups. The area under the ROC curve (AUC) for [TIMP2]•[IGFBP7] in predicting AKI in the first seven days was 0.633 (95% CI 0.588–0.678), for the overall cohort, with sensitivity and specificity of 66.1 and 51.9% respectively. When we considered patients with combined sepsis, trauma, and respiratory disease we found a higher AUC than patients without these conditions (0.711 vs. 0.575; p=0.002).


The accuracy of [TIMP2]•[IGFBP7] in predicting the risk of AKI in the first seven days after ICU admission has significant variability when the reason for ICU admission is considered.

Corresponding author: Bo Yang, Department of Nephrology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, PR China; and International Renal Research Institute of Vicenza, San Bortolo Hospital, Viale Rodolfi 37, 36100Vicenza, Italy, E-mail:


The authors are grateful to Gregorio Aramid Romero González, Alejandra Molano Trivino, Ana De Castro, and all the fellows of the International Renal Research Institute of Vicenza who helped in the study.

  1. Research funding: None declared.

  2. Author contributions: CR, BY, YX, FG and RB contributed to study design. BY, YX, GA and AP contributed to data collection. AB and FF contributed to patient enrollment. DG and MC contributed to laboratory work. FG, EV and GD contributed to statistical analysis. BY, GA, AP and CR contributed to manuscript writing and editing. All authors read and approved the final manuscript. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: CR is a consultant for Astute Medical, Ortho, and Biomerieux. All the other authors declared no competing interests.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The study was approved by the Institutional Ethics Committee of San Bortolo Hospital, Vicenza, Italy (Comitato Etico provinciale aULSS 8 Vicenza) (Exp. number: 03/17). The clinical investigation was conducted according to the principles expressed in the Declaration of Helsinki.


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Received: 2020-05-07
Accepted: 2020-09-11
Published Online: 2020-09-28
Published in Print: 2021-02-23

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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