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©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Neutrophil gelatinase-associated lipocalin does not predict acute kidney injury in heart failure
Fiorenza Ferrari, Elisa Scalzotto, Pasquale Esposito, Sara Samoni, Flavio Mistrorigo, Lilia Maria Rizo Topete, Massimo De Cal, Grazia Maria Virzì, Valentina Corradi, Rossella Torregrossa, Roberto Valle, Stefania Bianzina, Nadia Aspromonte, Matteo Floris, Alessandro Fontanelli, Alessandra Brendolan, Claudio Ronco
Fiorenza Ferrari, Elisa Scalzotto, Sara Samoni, Lilia Maria Rizo Topete, Massimo De Cal, Grazia Maria Virzì, Valentina Corradi, Alessandra Brendolan, Claudio Ronco, Department of Nephrology Dialysis & Transplantation, International Renal Research Institute Vicenza, St. Bortolo Hospital, Vicenza 36100, Italy
Pasquale Esposito, Department of Internal Medicine, Nephrology, Dialysis and Transplantation Clinics, Genoa University and IRCCS Policlinico San Martino, Genova 16132, Italy
Flavio Mistrorigo, Alessandro Fontanelli, Department of Cardiology, Coronary Intensive Care Unit, St. Bortolo Hospital, Vicenza 36100, Italy
Rossella Torregrossa, Roberto Valle, Department of Cardiology Coronary, Intensive Care Unit, Chioggia Hospital, Venezia 36100, Italy
Stefania Bianzina, Neonatal and Pediatric Intensive Care Unit, G. Gaslini Institute, Genoa 16147, Italy
Nadia Aspromonte, Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart Agostino Gemelli Foundation, Rome 00168, Italy
Matteo Floris, Division of Nephrology and Dialysis, Azienda Ospedaliera G. Brotzu, Piazzale Ricchi n°1, Cagliari 09134, Italy
Author contributions: Ferrari F, Brendolan A and Ronco C had full access to all the data in the study and assume full responsibility for the integrity of the data and the accuracy of the data analysis; Ferrari F and Scalzotto E equally contributed to the concept, design, analysis and interpretation of the data and the drafting of the paper. Both are first-time authors. Ferrari F, Scalzotto E and Esposito P contributed to the concept, design, analysis and interpretation of data; Floris M, Torregrossa R, Valle R, Aspromonte N and Fontanelli A acquired the data; De Cal M, Corradi V and Virzì GM performed the analytica determinations; Ferrari F contributed to statistical analysis; Ferrari F, Scalzotto E, Bianzina S and Esposito P drafted the paper; Samoni S, Brendolan A, Rizo Topete LM and Ronco C critically revised the paper for important intellectual content and finally approved the version to be published.
Institutional review board statement: The Ethical Committee of San Bortolo Hospital of Vicenza approved this study. The consent to participate is pursuant to Italian laws.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: Ronco C is a consultant of Astute Medical, OCD, Asahi Medical, Baxter, Toray Medical. None of the other authors have any financial interest related to this study to disclose. DC received an honorarium from Inverness Medical Inc. for a speech.
Data sharing statement: The datasets used and/or analyzed during the present study are available from the corresponding authors on reasonable request.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Pasquale Esposito, MD, PhD, Associate Professor, Department of Internal Medicine, Nephrology, Dialysis and Transplantation Clinics, Genoa University and IRCCS Policlinico San Martino, Viale Benedetto XV, Genova 16132, Italy.
pasqualeesposito@hotmail.com
Received: January 15, 2020
Peer-review started: January 15, 2020
First decision: February 26, 2020
Revised: April 1, 2020
Accepted: April 21, 2020
Article in press: April 21, 2020
Published online: May 6, 2020
Processing time: 105 Days and 23.7 Hours
BACKGROUND
Acute cardiorenal syndrome type 1 (CRS-1) is defined by a rapid cardiac dysfunction leading to acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) is expressed on the surface of human neutrophils and epithelial cells, such as renal tubule cells, and its serum (sNGAL) and urinary have been used to predict AKI in different clinical settings.
AIM
To characterize CRS-1 in a cohort of patients with acute heart diseases, evaluating the potentiality of sNGAL as an early marker of CRS-1.
METHODS
We performed a retrospective cohort, multi-centre study. From January 2010 to December 2011, we recruited 202 adult patients admitted to the coronary intensive care unit (CICU) with a diagnosis of acute heart failure or acute coronary syndrome. We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission.
RESULTS
Overall, enrolled patients were hemodynamically stable with a mean arterial pressure of 92 (82-107) mmHg, 55/202 (27.2%) of the patients developed CRS-1, but none of them required dialysis. Neither the NGAL delta value (AUC 0.40, 95%CI: 0.25-0.55) nor the NGAL peak (AUC 0.45, 95%CI: 0.36-0.54) or NGAL cut-off (≥ 140 ng/mL) values were statistically significant between the two groups (CRS-1 vs no-CRS1 patients). The area under the ROC curve for the prediction of CRS-1 was 0.40 (95%CI: 0.25-0.55) for the delta NGAL value and 0.45 (95%CI: 0.36-0.54) for the NGAL peak value. Finally, in multivariate analysis, the risk of developing CRS-1 was correlated with age > 60 years, urea nitrogen at admission and 24 h-urine output (AUC 0.83, SE = 60.5% SP = 93%), while sNGAL was not significantly correlated.
CONCLUSION
In our population, sNGAL does not predict CRS-1, probably as a consequence of the mild renal injury and the low severity of heart disease. So, these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.
Core tip: Renal and cardiac injuries are often interrelated, leading to high-risk clinical conditions. In this retrospective study, we evaluated the onset of acute kidney injury in 202 patients affected by acute heart disease [classified as cardiorenal syndrome-1 (CRS-1)], testing the potentiality of serum neutrophil gelatinase-associated lipocalin as a predictive marker of renal damage. Although the prevalence of CRS-1 in our population (27.2%) was consistent with that found in the literature, serum neutrophil gelatinase-associated lipocalin was not associated with CRS-1 development, probably as a consequence of the mild renal and cardiac injuries present in our study population. These data suggest that patient selection is crucial when considering the use of biomarkers.
