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L E T T E R

Open Access

NephroCheck: should we consider urine

osmolality?

Alberto Noto

1,3*

, Andrea Cortegiani

2

and Antonio David

1 Early detection of acute kidney injury (AKI) is challen-ging due to the risk of morbidity and mortality and a direct impact on patients’ management [1]. The diagno-sis relies on the changes of serum creatinine and urine output [2], which are the main markers of kidney func-tion. Recently, Astute Medical introduced the Nephro-Check, a test that allows a bedside analysis of two biomarkers of renal damage implicated in G1 cell-cycle ar-rest: tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) [3]. The combination of these two biomarkers led to a new score (AKIRisk™). An AKIRisk™ score > 0.3 identifies pa-tients at risk of developing AKI with sensitivity and speci-ficity of 92% and 46%, respectively; increasing the cutoff to 2.0, the sensitivity is 46% and the specificity is 95% [4]. The AKIRisk™ reference interval in healthy humans ranges from 0.04 to 2.22. A possible reason for this wide range could be that the score is not taking into account urine concentration.

We aimed to check the correlation between AKIRisk™

and urine osmolality, using a dehydration test. We col-lected urine samples from healthy volunteers after 8 h of operating room shift without drinking water (T0) and

after drinking 0.5 l of water (T1). Urine samples were an-alyzed, and osmolality as well as biomarker concentra-tion were measured. Complete measurements are reported in Additional file1: Table S1. A significant

dif-ference was found between the mean AKIRisk™ at T0

(0.82, 95% CI 0.15 to 1.48) vs. T1 (0.24, 95% CI 0.02 to 0.50),p = 0.01 (Wilcoxon test—Fig.1a). The Pearson cor-relation between osmolality and AKIRisk™ at T0 and T1 wasr = 0.93, p = 0.02, and r = 0.80, p = 0.03 (Fig.1b, c).

Our results suggest that fluid intake in the normal population is able to modify the urinary concentration of TIMP-2 and IGFB-7. It is to note that every AKIRisk™ > 0.3 occurs in people with urine osmolality > 600 mOsm/kg and that there is a good correlation between urine osmolality and AKIRisk™. Some participants still maintained AKIRisk™ > 0.3 even after fluid reintegration, maintaining a good correlation with urinary osmolality also at T1, indicating a suboptimal dehydration correction.

Our data suggest that the values of AKIRisk™ score

could be related to the urine concentration; thus, urine osmolality should be considered in the interpretation of the results of the NephroCheck® test. This correlation should be checked in critically ill patients at risk of AKI.

* Correspondence:alberto.noto@unime.it

1

Department of Anesthesia and Intensive Care, A.O.U. G.Martino, University of Messina, Italy, Via Consolare Valeria 1, 98100 Messina, Italy

3National Reaserch Council (CNR), Institute for Chemical and Physical Processes (IPCF), Messina, Italy

Full list of author information is available at the end of the article

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Notoet al. Critical Care (2019) 23:48 https://doi.org/10.1186/s13054-019-2341-9

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Additional file

Additional file 1:Raw data. Urine osmolality and AKIRisk score of each patient. (DOCX 43 kb)

Acknowledgements None.

Funding None.

Availability of data and materials Not applicable.

Authors’ contributions

AN, AC, and AD conceived the content and wrote and approved the final version of the manuscript.

Ethics approval and consent to participate Not applicable.

Consent for publication Not applicable. Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Author details 1

Department of Anesthesia and Intensive Care, A.O.U. G.Martino, University of Messina, Italy, Via Consolare Valeria 1, 98100 Messina, Italy.2Department of Surgical, Oncological and Oral Science (Di.Chir.On.S.), Section of Anesthesia, Analgesia, Intensive Care and Emergency, Policlinico Paolo Giaccone, University of Palermo, Palermo, Italy.3National Reaserch Council (CNR), Institute for Chemical and Physical Processes (IPCF), Messina, Italy.

Received: 22 January 2019 Accepted: 1 February 2019

References

1. Martin C, Cortegiani A, Gregoretti C, Martin-Loeches I, Ichai C, Leone M et al. Choice of fluids in critically ill patients. BMC Anesthesiology. 2018;18:200. 2. Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury

Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Inter. 2012;2:1–138.

3. Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17:R25.

4. Bihorac A, Chawla LS, Shaw AD, Al-Khafaji A, Davison DL, Demuth GE, et al. Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication. Am J Respir Crit Care Med. 2014;189:932–9. Fig. 1 a AKIRisk score measured at dehydration (T0) and after hydration (T1). b, c Relationship between urine osmolality and AKIRisk score measured by NephroCheck at T0 and T1. Red line represents the AKIRisk cutoff

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