Ann Lab Med 2017; 37(5): 388-397  https://doi.org/10.3343/alm.2017.37.5.388
Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis
Hanah Kim, M.D.1, Mina Hur, M.D.1, Seungho Lee, Ph.D.2, Rossella Marino, M.D.3, Laura Magrini, M.D.3, Patrizia Cardelli, M.D.4, Joachim Struck, Ph.D.5, Andreas Bergmann, Ph.D.5, Oliver Hartmann, Ph.D.5, and Salvatore Di Somma, M.D.3; on behalf of the GREAT Network
Department of Laboratory Medicine1, Konkuk University School of Medicine, Seoul, Korea; School of Public Health2, Seoul National University, Seoul, Korea; Departments of Medical-Surgery Sciences and Translational Medicine3, and Clinical and Molecular Medicine4, School of Medicine and Psychology, ‘Sapienza’ University, Sant’Andrea Hospital, Rome, Italy; Sphingotec GmbH5, Hennigsdorf, Germany
Correspondence to: Mina Hur
Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea
Tel: +82-2-2030-5581 Fax: +82-2-2636-6764 E-mail: dearmina@hanmail.net
Salvatore Di Somma
Department of Medical-Surgery Sciences and Translational Medicine, University La Sapienza Rome, Sant’ Andrea Hospital, Via di Grottarossa 1035/1039 00189 Rome, Italy
Tel: +39-0633775581 Fax: +39-0633775890 E-mail: salvatore.disomma@uniroma1.it
Received: November 8, 2016; Revised: March 2, 2017; Accepted: April 19, 2017; Published online: September 1, 2017.
© The Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients.
Methods: A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPICr, CDK-EPICysC, and CKD-EPICr-CysC. The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes.
Results: The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality.
Conclusions: PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis.
Keywords: Proenkephalin, Neutrophil gelatinase-associated lipocalin, Glomerular filtration rate, Sepsis, Acute kidney injury


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