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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
ARTICLE HIGHLIGHTS
Research background
Cardiac and renal diseases frequently coexist, leading to significantly increased mortality, morbidity and increased care cost. Syndromes describing the interaction between heart and kidney have been defined as "cardiorenal syndrome" (CRS). In particular, acute cardiorenal syndrome type 1 (CRS-1) is defined by a rapid cardiac dysfunction leading to acute kidney injury (AKI). Several biomarkers of kidney injury have shown diagnostic and prognostic value. Among them, neutrophil gelatinase-associated lipocalin (NGAL) has shown promising perspectives.
Research motivation
Due to the high potential clinical impact, the definition and characterization of validated biomarkers may be of help in the prevention and treatment of AKI and CRS-1.
Research objectives
The primary aim of this study was 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.
Research methods
We performed a retrospective cohort, multicenter study. From January 2010 to December 2011, we evaluated 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.
Research results
202 patients affected by acute heart disease were enrolled. Out of them, 55 patients (27.2%) developed CRS-1, but none 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 two groups of patients (CRS-1 vs no-CRS1). 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. 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.
Research conclusions
We found that in our population, although the prevalence of CRS-1 (27.2%) was consistent with that found in the literature, sNGAL levels were not associated with a decline in renal function defined by creatinine changes. This finding could be, at least in part, a consequence of the mild renal and cardiac injuries present in our study population, which might have reduced the potential of sNGAL as a biomarker.
Research perspectives
Our data underline that further studies are warranted to define the profile of biomarkers for predicting AKI, considering that patient selection and characterization could significantly influence the performance of the different biomolecules.
