Clinical Impact of Kidney Function on Presepsin Levels

RESEARCH ARTICLE Clinical Impact of Kidney Function on Presepsin Levels Takanobu Nagata1, Yoshinari Yasuda1, Masahiko Ando2, Tomoko Abe1, Takayuki Katsuno1, Sawako Kato1, Naotake Tsuboi1, Seiichi Matsuo1, Shoichi Maruyama1* 1 Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Japan, 2 Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan * Abstract Objective OPEN ACCESS Citation: Nagata T, Yasuda Y, Ando M, Abe T, Katsuno T, Kato S, et al. (2015) Clinical Impact of Kidney Function on Presepsin Levels. PLoS ONE 10(6): e0129159. doi:10.1371/journal.pone.0129159 Academic Editor: Dirce Maria Trevisan Zanetta, School of Public Health of University of São Paulo, BRAZIL Received: November 25, 2014 Accepted: May 5, 2015 Published: June 1, 2015 Copyright: © 2015 Nagata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by Kyowa Hakko Kirin Co., Ltd. Otsuka Pharmaceutical Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., and Mochida Pharmaceutical Co., Ltd. provided support in the form of research grants for authors [TN, YY, MA, TA, TK, SK, NT, SM, SM], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section. Presepsin is highlighted as a diagnostic and prognostic marker of sepsis. Little information is available regarding the accurate association between presepsin levels and the degree of kidney function. We analyzed presepsin levels in patients with a glomerular filtration rate (GFR) in the categories G1 to G5, evaluated via inulin renal clearance test, and receiving hemodialysis (HD). Methods Patients who were not receiving HD were included if they had undergone inulin renal clearance measurements for the accurate measurement of GFR (measured GFR), and patients who were receiving hemodialysis (HD) were included if they had anuria. Exclusion criteria were infection, cancer, liver disease, autoimmune disorders, or steroid or immunosuppressant use. GFR category was defined as follows; G1: GFR  90 ml/min/1.73m2, G2: GFR = 60 to 90 ml/min/1.73m2, G3: GFR = 30 to 60 ml/min/1.73m2, G4: GFR = 15 to 30 ml/min/ 1.73m2, G5: GFR  15 ml/min/1.73m2. Results Seventy-one patients were included. The median (IQR) presepsin values of patients in each GFR category were as follows: G1 + G2: 69.8 (60.8–85.9) pg/ml; G3: 107.0 (68.7– 150.0) pg/ml; G4: 171.0 (117.0–200.0) pg/ml; G5: 251.0 (213.0–297.5) pg/ml; and HD: 1160.0 (1070.0–1400.0) pg/ml. The log-transformed presepsin values, excluding patients receiving HD, inversely correlated with the measured GFR (Pearson’s correlation coefficient = -0.687, P < 0.001). The multivariate analysis revealed that measured GFR and hemoglobin levels significantly correlated with elevated presepsin levels. Conclusion Presepsin levels were markedly high in patients receiving HD, similar to values seen in patients with severe sepsis or septic shock. In patients who were not receiving HD, presepsin PLOS ONE | DOI:10.1371/journal.pone.0129159 June 1, 2015 1 / 10 Kidney Function and Presepsin Levels Competing Interests: The authors declare the following competing interests: Kyowa Hakko Kirin Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Dainippon Sumitomo Pharma Co., Ltd., and Mochida Pharmaceutical Co., Ltd. provided support in the form of research grants for authors [TN, YY, MA, TA, TK, SK, NT, SM, SM], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. levels increased as GFR decreased. Thus, the evaluation of presepsin levels in patients with chronic kidney disease requires further consideration, and a different cutoff value is needed for diagnosing sepsis in such patients. Introduction Sepsis is a major cause of mortality in patients presenting to the emergency department (ED) or intensive care unit (ICU). Early recognition and treatment initiation are essential for improving the prognosis of patients with sepsis [1,2,3]. Various biomarkers such as procalcitonin (PCT) have been used for diagnosing sepsis [4,5]. Although PCT level often indicates the presence of infection, its levels are also elevated in various conditions that induce systemic inflammatory response syndrome, such as severe trauma, burn injury, or surgical procedures [6,7]. Therefore, it is necessary to develop a biomarker that is more specific and that can be used for the earlier detection of sepsis compared to PCT. Presepsin is the soluble N-terminal fragment of the cluster of differentiation (CD) marker protein CD14, which is the receptor for lipopolysaccharide (LPS) and LPS-binding protein complexes [8]. Recently, presepsin was reported as valuable for the early diagnosis of sepsis and the evaluation of sepsis severity, and its levels remain unaffected by conditions such as trauma, burn injury, or surgical procedures [8,9]. The diagnostic cutoff levels for sepsis varied among different studies, but most reports suggest approximate levels of 400–600 pg/ml [8,10]. In addition, based on experiments with septic animal models, presepsin levels increase 2 hours after the onset of infection, which is earlier than the elevation of PCT levels [11,12]. Moreover, some studies have reported that the measurement of presepsin levels is useful for predicting the prognosis of septic patients [10,13,14,15]. Because of these characteristics, presepsin is being used in various clinical situations. However, there is a concern that presepsin level is affected by kidney function. Presepsin is a 13 kDa protein. Although its exact in vivo activity is unclear, it is presumed from its molecular weight that presepsin is filtered by the glomerulus, reabsorbed, and catabolized within proximal tubular cells [16]. Theoretically, it has been proposed that presepsin levels increase as kidney function decreases. Chenevier-Gobeaux et al. [16] measured presepsin levels in patients who presented to the ED with mild illness without acute infection. They showed that presepsin levels were elevated in most patients with a decreased estimated glomerular filtration rate (eGFR; <60 ml/min/1.73m2). Behnes et al. [17] reported that, in an internal ICU, presepsin levels significantly correlated with serum creatinine levels and the number of days on renal replacement therapy, which are both related to kidney function. Nakamura et al. [18] retrospectively analyzed presepsin level (...truncated)