Correlation between urinary biomarker and organ failure in patients with sepsis and patients after esophagectomy: a prospective observational study

Mitaka et al. Journal of Intensive Care (2020) 8:11 https://doi.org/10.1186/s40560-020-0428-7 RESEARCH Open Access Correlation between urinary biomarker and organ failure in patients with sepsis and patients after esophagectomy: a prospective observational study Chieko Mitaka1* , Chika Ishibashi1, Izumi Kawagoe1, Takashi Hashimoto2, Makoto Takahashi3, Daizoh Satoh1 and Eiichi Inada1 Abstract Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a diagnostic marker for acute kidney injury (AKI). NGAL expression is highly induced not only in kidney injury but also in bacterial infection, inflammation, and cancer. The factors regulating NGAL expression are proinflammatory cytokines, and plasma NGAL levels have been increased in septic shock. However, there are no reports of urine neutrophil gelatinase-associated lipocalin (uNGAL) levels after open esophagectomy. Methods: We prospectively enrolled critically ill patients, including patients with sepsis (n = 45) and patients who underwent open esophagectomy (n = 40). We compared vital signs, PaO2/FIO2, serum C-reactive protein (CRP) levels, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and uNGAL levels between the sepsis group and the esophagectomy group. Then, we investigated whether uNGAL is associated with the severity of illness and organ failure, and whether uNGAL is a reliable screening test for AKI. Results: The median uNGAL levels, APACHE II score, SOFA score, and serum CRP levels were significantly (p < 0.001) higher in the sepsis group than in the esophagectomy group on ICU day 1. In the sepsis group, uNGAL levels were significantly (p < 0.05) correlated with APACHE II score and SOFA score on intensive care unit (ICU) day 1, 2, and 3. In the esophagectomy group, uNGAL levels were significantly (p < 0.05) correlated with SOFA score on ICU day 3 and 4. In the sepsis group, 1 patient developed AKI stage 2 and 6 patients developed AKI stage 3. No patients developed AKI in the esophagectomy group. In a total of 85 patients of this study, 80 patients had an abnormal value of uNGAL and only 7 patients (8.7%) of those 80 patients developed AKI. Conclusions: uNGAL levels were correlated with the severity of illness and organ failure in critically ill patients. The value of uNGAL increases under the surgical and inflammatory responses, thereby losing a significance of a screening test of AKI in critically ill patients. Keywords: Acute kidney injury, Biomarker, Esophageal cancer, Esophagectomy, NGAL (neutrophil gelatinaseassociated lipocalin), Organ dysfunction, Sepsis, Severity * Correspondence: 1 Department of Anesthesiology and Pain Medicine, Juntendo University Faculty of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo 113-8431, Japan Full list of author information is available at the end of the article © The Author(s). 2020 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. Mitaka et al. Journal of Intensive Care (2020) 8:11 Background Neutrophil gelatinase-associated lipocalin (NGAL), a 25 kDa protein of the lipocalin family, is a diagnostic marker for acute kidney injury (AKI) [1–3]. NGAL expression is highly induced not only in kidney injury [4, 5] but also bacterial infection, inflammation, and cancer [6–9]. The factors regulating NGAL expression are proinflammatory cytokines such as interleukins, tumor necrosis factor-α and interferons [7]. In fact, plasma NGAL levels have been increased in patients with septic shock [10–12]. On the other hand, open esophagectomy for esophageal cancer performed through a right-thoracotomy and laparotomy is a major invasive surgery [13, 14]. Surgical stress of radical esophagectomy induces the release of interleukin-6 and interleukin-8 and the overproduction of these cytokines induces systemic inflammatory response syndrome [15]. Therefore, open esophagectomy has a higher risk of intraoperative and postoperative complications. Although NGAL is highly expressed in esophageal squamous cell carcinoma [8, 9], there are no reports of uNGAL levels after open esophagectomy. In addition, NGAL is released from the lung, bronchi, and esophagus [7]. Therefore, we surmised that NGAL might be released from various organs such as the lung, bronchi, and esophagus during and after esophagectomy. The design of the present study required the selection of patients at risk for organ dysfunction. Therefore, we prospectively recruited critically ill patients with sepsis and patients after open esophagectomy with gastric reconstruction for esophageal cancer. Accordingly, we investigated in critically ill patients whether uNGAL is associated with the severity of illness and organ failure, and whether uNGAL is a reliable screening test for AKI. Methods Study design and patients This CUBIC (correlation between urinary biomarker and organ failure in critically ill patients) study was a prospective observational study. The study protocol was approved by the Ethics Committee of Juntendo University Hospital. This study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed written consent was obtained from patients or close relatives. This study was registered with the University Hospital Medical Information Network (UMIN 000024155). From January 2017 to April 2019, we prospectively enrolled 85 critically ill patients who were admitted to the intensive care unit (ICU) at the Juntendo University Hospital. Patients were followed up for 90 days after enrollment. The inclusion criteria were age ≥ 20 years, critically ill patients with either sepsis or open esophagectomy with gastric reconstruction for esophageal cancer. Sepsis was Page 2 of 8 defined as an increase in sequential organ failure assessment (SOFA) score [16] ≥ 2 points caused by a dysregulated host response to infection according to definitions for Sepsis-3 [17]. The exclusion criteria were end-stage kidney disease and renal replacement therapy prior to intensive care unit (ICU) admission or kidney transplant. End-stage kidney disease is defined by a need for dialysis longer than 3 months [18]. Data collection Demographic data for each participant were collected, including age, gender, and underlying diseases. The vital signs and arterial blood gas of each patient were measured and recorded. Routine blood tests including Creactive protein (CRP) level were condu (...truncated)