Original article
Relationship between acute kidney injury and serum procalcitonin (PCT) concentration in critically ill patients with influenza infection
Relación entre disfunción renal aguda y valores séricos de procalcitonina en pacientes críticos con infección por gripe
A. Rodrígueza,
, L.F. Reyesb, J. Moncloua, B. Suberviolac, M. Bodía, G. Sirgoa, J. Solé-Violánd, J. Guardiolae, D. Barahonaf, E. Díazg, I. Martín-Loechesh, M.I. Restrepob, on behalf GETGAG study group 1
Autor para correspondencia
a Critical Care Department, Hospital Universitari de Tarragona Joan XXIII/IISPV/URV/CIBERes, Tarragona, Spain
b Division of Pulmonary Diseases and Critical Care Medicine University of Texas Health Science Center at San Antonio San Antonio, TX, USA
c Critical Care Department, Hospital Universitario Marqués de Valdecilla, Santander, Spain
d Critical Care Department, Hospital Dr. Negrín, Las Palmas de Gran Canaria, Spain
e Division of Pulmonary, Critical Care and Sleep Medicine, University of Louisville and Robley Rex VA Medical Center, Louisville, KY, USA
f Critical Care Department, Hospital Docente de Calderón, Quito, Ecuador
g Critical Care Department, ParcTaulí Hospital/CIBERes, Sabadell, Spain
h Multidisciplinary Intensive Care Research Organization (MICRO), Department of Anaesthesia and Critical Care, St James's University Hospital, Trinity Centre for Health Sciences, Dublin, Ireland
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Each point in the scatterplot represents the value of two variables for a given observation. The low rank Spearman correlation coefficient (rho<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.18) confirms that Cr and PCT are not correlated strongly.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Procalcitonin (PCT) is an acute-phase protein released into the bloodstream mainly in response to bacterial infection.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1–4</span></a> Its sensitivity and specificity for bacterial infections is around 0.77 and 0.79, respectively, with an area under the curve (AUC) that has been reported as high as 0.85.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> However, serum PCT concentrations can be increased during inflammatory conditions in the absence of bacterial infection.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> PCT is eliminated by kidney clearance, thus, high concentrations of PCT in patients with chronic or acute kidney dysfunctions are frequently interpreted as non-bacterial infection related elevations.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2–7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Several studies have found increased PCT levels in patients presenting with chronic kidney disease, peritoneal dialysis and oliguria in the absence of bacterial infections.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8–13</span></a> A recent meta-analysis,<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> including studies with high heterogeneity, reported that in patients with chronic kidney disease (CKD), PCT might have poor sensitivity (73%) but acceptable specificity (88%) for the diagnosis of bacterial infection. Nevertheless, the best cut-off value of PCT in patients with acute kidney injury (AKI) remains unknown and the real relation among creatinine/urea and PCT concentration are not clear. Moreover, the underlying mechanisms of PCT elevation in these patients are not fully understood.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Our hypothesis is that low concentrations of PCT are accurate in order to rule out bacterial coinfection in patients with influenza pneumonia admitted to the intensive care unit (ICU), but higher PCT levels should be carefully interpreted in patients with acute kidney injury (AKI). In this context, the primary goal of this study was to determine the relation between AKI (using creatinine and urea as surrogate markers of AKI) and PCT concentrations in critically ill patients with influenza pneumonia without bacterial co-infection.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Study design and patient population</span><p id="par0020" class="elsevierStylePara elsevierViewall">This was a pre-planned secondary analysis of a prospective, observational, multicentre cohort study conducted in 148 ICUs in Spain between June 2009 and April 2014. Data were obtained from a voluntary registry created by the Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC). The study was approved by the Joan XXIII University Hospital Ethics Committee (#11809). The requirement for informed consent was waived due to the observational nature of the study, as reported elsewhere.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">15–18</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Inclusion and exclusion criteria</span><p id="par0025" class="elsevierStylePara elsevierViewall">All patients admitted to the ICU with influenza symptoms were systematically tested to confirm influenza A, B, or C infection. Influenza virus infection was confirmed by real-time reverse-transcription polymerase chain reaction (PCR) in all subjects as previously reported.<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">15–18</span></a> Only patients with PCT measured on ICU admission were included in the analysis.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Patients with bacterial co-infection previous to ICU admission, with CKD and AKIN 3 (creatinine levels ≥4<span class="elsevierStyleHsp" style=""></span>mg/dL) were excluded from the study. Additionally, patients receiving renal replacement therapies (RRT) were excluded due to potential PCT elimination by RRT.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8,9,12,19</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Patients were considered to have bacterial co-infection when a respiratory bacterial pathogen was identified within the first two days of ICU admission. In patients under mechanical ventilation, a respiratory specimen was obtained upon admission to the ICU according to local protocols. In addition, patients were tested for <span class="elsevierStyleItalic">Streptococcus pneumoniae</span> and <span class="elsevierStyleItalic">Legionella maltophilia</span> using urinary antigens as previously described.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Acute kidney injury definition</span><p id="par0040" class="elsevierStylePara elsevierViewall">AKI was defined according to the current Acute Kidney Injury Network (AKIN) definitions.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> Importantly, we only used creatinine levels because we were unable to record information on urinary output. The cohort was stratified into three groups as follows: (a) AKI 0: no AKI, (b) AKI I: with creatinine levels between 1.60 and 2.50<span class="elsevierStyleHsp" style=""></span>mg/dL and (c) AKI II: with creatinine levels between 2.51 and 3.99<span class="elsevierStyleHsp" style=""></span>mg/dL.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Variables recorded</span><p id="par0045" class="elsevierStylePara elsevierViewall">The following variables were collected: demographic data, comorbidities, need for mechanical ventilation, vasopressor usage and laboratory findings. To determine the severity of illness, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> was calculated in all patients within 24<span class="elsevierStyleHsp" style=""></span>h of ICU admission. For linear regression analysis, a modified APACHE II score without renal dysfunction points was used. Organ failure was assessed using the Sequential Organ Failure Assessment (SOFA) scoring system.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> Further definitions are presented in the supplementary electronic material.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Laboratory testing</span><p id="par0050" class="elsevierStylePara elsevierViewall">PCT is not part of the biomarkers recommended for the diagnosis of community-acquired pneumonia (CAP) by the Spanish guidelines.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> The decision to assess serum PCT upon ICU admission was left to the discretion of the attending physician and was not standardized per protocol. PCT was measured using B·R·A·H·M·S PCT automated immunoassays. The analytical sensitivity of all assays was <0.05<span class="elsevierStyleHsp" style=""></span>μg/L. All techniques were based on a one-step immunoassay sandwich method determined either by chemiluminescence or fluorescence.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Study end-points</span><p id="par0055" class="elsevierStylePara elsevierViewall">The primary endpoint of this analysis was to evaluate the relationship between both serum levels of renal biomarkers (creatinine and urea) and serum levels of PCT upon ICU admission. The secondary end-point was to determine the relative contribution of creatinine/urea on PCT concentrations.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Statistical analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">First, we determine the strength of relationship between creatinine and urea with PCT levels by linear correlation analysis (Spearman's rank correlation). Second, we determine extreme outliers using a box-plot of PCT concentrations. We define very extreme outliers as Q3<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>3 IQR (interquartile range). Third, to evaluate the relative impact of serum levels of creatinine and urea on PCT concentrations, simple and multiple linear regressions were used. Linear regression analyses with and without very extreme outlier values were performed. Fourth, to determine the relative contribution of clinically important covariates (creatinine, urea, modified APACHE II, white cell counts, and chronic heart disease) on PCT concentrations, a multiple linear regression analysis was performed. Previously, we tested their interaction by using the product of the two explanatory variables in a multiple linear regression. For this, we included the new variables (creatinine<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>modified APACHE; creatinine<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>white cell counts; creatinine<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>chronic heart disease; modified APACHE II<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>white cell counts; APACHE II modified<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>chronic heart disease; white cell counts<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>chronic heart disease; Urea<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>modified APACHE II, urea<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>white cell count and urea<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>chronic heart disease) in a multiple linear regression analysis and only significant variables (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) were added to the final model.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Discrete variables are expressed as counts (percentages), and continuous variables are expressed as medians with the 25th–75th interquartile ranges (IQR). For patient demographics and clinical characteristics, the differences between the groups were assessed using the <span class="elsevierStyleItalic">X</span><span class="elsevierStyleSup">2</span> test and Fisher's exact test for categorical variables and Student's <span class="elsevierStyleItalic">t</span>-test or Mann–Whitney <span class="elsevierStyleItalic">U</span> test or ANOVA (K-Wallis) for continuous variables. Data analysis was performed using IBM SPSS for Windows 22.0 software. All <span class="elsevierStyleItalic">p</span> values were two-sided, and statistical significance was defined as <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">Two thousand one hundred and thirty-two patients with PCR-confirmed influenza pneumonia were admitted to the 148 ICUs. PCT was measured in 972 (45.6%) patients at the time of ICU admission. A total of 633 (65%) patients were included in the study (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Among them, 571 (90.2%) did not develop AKI, whereas 52 (8.2%) and 10 (1.6%) were categorized as AKI I and II, respectively. Further details regarding renal function and clinical characteristics are presented in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#sec0110">Table 1e (electronic material)</a>. PCT concentrations were higher in patients with AKI (2.62<span class="elsevierStyleHsp" style=""></span>ng/mL [IQR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.6–10.]) than in non-AKI patients (0.40<span class="elsevierStyleHsp" style=""></span>ng/mL [IQR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.13–1.20], <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002). AKI patients were older, had more major comorbidities, and were more severely ill, and had higher white cell counts upon ICU admission than those without AKI (<a class="elsevierStyleCrossRef" href="#sec0110">Table 1e</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Renal dysfunction and PCT relationship</span><p id="par0075" class="elsevierStylePara elsevierViewall">Patients had increased serum creatinine and urea levels according to PCT cut-off values (<a class="elsevierStyleCrossRef" href="#fig0010">A/B</a> and <a class="elsevierStyleCrossRef" href="#sec0110">Table 2e [electronic material]</a>). In overall population, we observed a significant, but weak correlation between both creatinine (rho<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.18; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001, <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) and urea (rho<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.19; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001, <a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>) levels and PCT concentration upon ICU admission.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Relative contribution of renal dysfunction to PCT concentrations</span><p id="par0080" class="elsevierStylePara elsevierViewall">To evaluate the relation among serum creatinine/urea with PCT levels, we first conducted a linear regression analysis and the results are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Using the standard outer fences formula, an extreme outlier was defined as PCT values >5.75<span class="elsevierStyleHsp" style=""></span>ng/mL. A linear regression analysis without extreme outliers was performed and no differences were observed in respect of the initial analysis with extreme outliers (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). For creatinine (without outlier values), <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span> was 0.03 (SD<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.5), which suggests that the creatinine levels could explain only 3% of the variability of PCT. Similar results were obtained when logarithmic transformation of data was performed (<span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001; <a class="elsevierStyleCrossRef" href="#sec0110">Figure 2e of the electronic material</a>). On the other hand, <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span> (without outliers) for urea was 0.018 (SD<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.52), which suggests that only 2% of the variability of PCT could be explained by the urea levels. Similar results were obtained when logarithmic transformation of data was performed (<span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.010, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.013; <a class="elsevierStyleCrossRef" href="#sec0110">Figure 3e electronic material</a>). The results were similar when a regression analysis without outlier values was performed (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Impact of creatinine on PCT levels considering confounding factors and their interactions</span><p id="par0085" class="elsevierStylePara elsevierViewall">A multiple linear regression analysis was used to test the interaction between clinical and laboratory variables (<a class="elsevierStyleCrossRef" href="#sec0110">Table 4e electronic material</a>). Two sets of variables showed the best performance when the product of the two explanatory variables was analyzed (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05): creatinine<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>APACHE II score (CrAP) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 and creatinine<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>white cell counts (CrWCC) <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.009. Secondly, PCT (dependent variable), modified APACHE II score, serum creatinine, white cell counts, chronic heart disease, and the new variables (CrAP and CrWCC) were entered in the final model resulting in <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span> slightly increasing to 0.046 (SE<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10.0; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001, <a class="elsevierStyleCrossRef" href="#sec0110">Table 5e of the electronic material</a>). The final model suggests that only 5% of the variability of PCT could be explained by the confounding variables and their interactions.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Impact of urea on PCT levels considering confounding factors and their interactions</span><p id="par0090" class="elsevierStylePara elsevierViewall">None of the new variables tested were found to be adequate predictor variables using multiple linear regression analysis (<a class="elsevierStyleCrossRef" href="#sec0110">Table 6e electronic material</a>); therefore, were not included in the final model. PCT (dependent variable), modified APACHE II score, urea, white cell counts, and chronic heart disease were entered in the final model showing an <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.013 (SE<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10.2, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.08; <a class="elsevierStyleCrossRef" href="#sec0110">Table 7e electronic material</a>). These confounding factors or their interactions based on the final model could not explain the variability of the PCT.</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Discussion</span><p id="par0095" class="elsevierStylePara elsevierViewall">The main conclusion of our study is that the contribution of renal dysfunction (assessed by creatinine and urea levels) on increased PCT concentration is poor. Although PCT values were increased in patients with AKI and creatinine, and urea correlated significantly with PCT, this correlation was very weak. Therefore, the relative contribution of renal dysfunction to PCT values is not greater than 5% in critically ill patients with influenza infection.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Very little is known about the elimination mechanisms of PCT; however, it is likely that renal function interferes with PCT values. Herget-Rosenthal et al.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> observed that serum PCT progressively increased in parallel to the deterioration of renal function. Importantly, although elevated, PCT levels in patients with chronic kidney disease stages I–IV did not markedly differ from those in healthy volunteers. Only in patients with chronic kidney disease stage V and those undergoing peritoneal dialysis, PCT concentrations were significantly higher when compared to healthy controls or patients with stages I–IV. The authors suggested that the progression of renal dysfunction and reduction in urine output could reduce the renal elimination of PCT. Dahaba et al.<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> observed in non-septic uremic patients a mean PCT plasma concentration of 1.82 (0.39)<span class="elsevierStyleHsp" style=""></span>ng/mL prior to the start of the first haemodialysis session. The authors suggested that uremia “<span class="elsevierStyleItalic">per</span>-<span class="elsevierStyleItalic">se</span>” is the principal origin of the increased concentrations of PCT; due to increased levels of serum cytokines. Importantly, this PCT concentration was lower than identified in our study, but our patients have a viral infection and the median value of PCT in patients without AKI was 0.4<span class="elsevierStyleHsp" style=""></span>ng/mL as previously reported in another study.<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> In contrast, Meisner et al.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> reported that renal elimination of PCT was not the mainstay mechanisms of PCT elimination.</p><p id="par0105" class="elsevierStylePara elsevierViewall">PCT synthesis has been identified in various tissues and cell types such as leukocytes, specifically in peripheral blood mononuclear cells.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">27,28</span></a> Activated peripheral blood mononuclear cells and pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF)-α and interleukin 1 (IL)-1, are considered to play a key role in the inflammatory process and were also shown to induce PCT production.<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> Some authors have observed a strong correlation between serum PCT and PCT released by peripheral blood mononuclear cells cultured in vitro<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a>: we did not observe any correlation between white cell counts and PCT levels (rho<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.45 data not shown). It is likely that the increase of pro-inflammatory cytokines may be the link between inflammation and elevated PCT levels in patients with chronic kidney disease, or those receiving renal replacement therapy. However, the role of this pathway in AKI requires further characterization.</p><p id="par0110" class="elsevierStylePara elsevierViewall">According to our results, we can expect predicted PCT values of 1.06<span class="elsevierStyleHsp" style=""></span>ng/mL, 1.67<span class="elsevierStyleHsp" style=""></span>ng/mL, 2.28<span class="elsevierStyleHsp" style=""></span>ng/mL and 2.89<span class="elsevierStyleHsp" style=""></span>ng/mL for creatinine values of 1, 2, 3, and 4<span class="elsevierStyleHsp" style=""></span>mg/dL, respectively. Although we observed a median value of PCT (1.93<span class="elsevierStyleHsp" style=""></span>ng/mL) similar to predicted PCT (1.67<span class="elsevierStyleHsp" style=""></span>ng/mL) in AKI I patients, the median value of PCT in AKI II patients (5.40<span class="elsevierStyleHsp" style=""></span>ng/mL) was higher than predicted PCT (2.28–2.89<span class="elsevierStyleHsp" style=""></span>ng/mL) by creatinine concentration. We cannot explain this finding, but we might hypothesize that unknown variables other than renal dysfunction, such white blood cells, severity of illness, chronic heart disease or presence of bacterial infection, might play a pivotal role in PCT release/elimination. Although the relative contribution of renal dysfunction to PCT levels is low according to our data, the use of a different PCT cut-off, adjusted to the level of renal dysfunction could increase its diagnostic utility when assessing the probability of bacterial coinfection in this special population of patients with influenza and AKI.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Some limitations in the design of our study must be acknowledged. First, we only assessed renal function using creatinine and urea. Even though these biomarkers are well accepted subrogates of renal function, international consensus recommends using urinary outputs,<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> unfortunately, these data was not collected during this study. Second, we examined the PCT levels only upon ICU admission. However, our main goal was to evaluate the relative contribution of AKI to basal PCT levels and not changes over time. Third, we excluded patients with AKI stage III and those who receive continuous renal replacement therapy because the PCT levels in these patients are difficult to interpret due to PCT release associated with microinflammation and/or blood contact with biocompatible membranes.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">3,4,8,22,24</span></a> Fourth, bacterial co-infection was ruled out by microbiology testing in respiratory samples and urinary antigens in patients under mechanical ventilation. However, we cannot certainly rule out bacterial coinfection in non-ventilated patient with only negative urinary antigens. Importantly, less than 20% of patients included in our study were non-ventilated. Finally, we considered only patients with influenza without bacterial infection and therefore our results cannot be generalized to all patients admitted to the ICU.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Conclusion</span><p id="par0120" class="elsevierStylePara elsevierViewall">Our study suggests that even though PCT levels in patients with AKI were higher, physicians should not continue thinking that high levels of PCT in patients with AKI are secondary to kidney dysfunction and should be aware of other causes of PCT elevation, including bacterial infections.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Funding/Role of the sponsors</span><p id="par0125" class="elsevierStylePara elsevierViewall">This study was supported by the Spanish Intensive Care Society (SEMICYUC) and Ricardo Barri Casanovas Foundation. The study sponsors have no role in the study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author (AR) had full access to all the data in the study and ultimate responsibility for the decision to submit it for publication.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Author contributions</span><p id="par0130" class="elsevierStylePara elsevierViewall">AR, IML, ED, MB, JSV, MIR, DB, GS and LFR conceived and designed the study. All authors, apart from MIR, LFR and DB, contributed to the acquisition and local preparation of the constituent database.</p><p id="par0135" class="elsevierStylePara elsevierViewall">AR, IML and MB contributed to database creation and standardization, design of statistical analyses, and data analysis.</p><p id="par0140" class="elsevierStylePara elsevierViewall">AR, IML, JSV, MIR, AGE, LFR, ED, GS, and BS interpreted the data and wrote the paper.</p><p id="par0145" class="elsevierStylePara elsevierViewall">All authors contributed to the critical examination of the paper for important intellectual content and approval of the final manuscript. Each author, apart from MIR, FLR and DB, acts as the guarantor of data from their individual center. AR acts as overall guarantor for the pooled analysis and the report.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Conflict of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1083573" "titulo" => "Abstract" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Design" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Setting" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Patients" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Interventions" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1028256" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1083572" "titulo" => "Resumen" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0045" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0050" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0055" "titulo" => "Diseño" ] 3 => array:2 [ "identificador" => "abst0060" "titulo" => "Lugar" ] 4 => array:2 [ "identificador" => "abst0065" "titulo" => "Pacientes" ] 5 => array:2 [ "identificador" => "abst0070" "titulo" => "Intervenciones" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1028257" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design and patient population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Inclusion and exclusion criteria" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Acute kidney injury definition" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Variables recorded" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Laboratory testing" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Study end-points" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0050" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Renal dysfunction and PCT relationship" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Relative contribution of renal dysfunction to PCT concentrations" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Impact of creatinine on PCT levels considering confounding factors and their interactions" ] 3 => array:2 [ "identificador" => "sec0070" "titulo" => "Impact of urea on PCT levels considering confounding factors and their interactions" ] ] ] 7 => array:2 [ "identificador" => "sec0075" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Funding/Role of the sponsors" ] 10 => array:2 [ "identificador" => "sec0090" "titulo" => "Author contributions" ] 11 => array:2 [ "identificador" => "sec0095" "titulo" => "Conflict of interest" ] 12 => array:2 [ "identificador" => "xack367655" "titulo" => "Acknowledgements" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-10-17" "fechaAceptado" => "2017-12-10" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1028256" "palabras" => array:5 [ 0 => "Procalcitonin" 1 => "Creatinine" 2 => "Urea" 3 => "Renal dysfunction" 4 => "Influenza" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1028257" "palabras" => array:5 [ 0 => "Procalcitonina" 1 => "Creatinina" 2 => "Urea" 3 => "Disfunción renal" 4 => "Gripe" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Serum procalcitonin (PCT) concentration could be increased in patients with renal dysfunction in the absence of bacterial infection.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To determine the interactions among serum renal biomarkers of acute kidney injury (AKI) and serum PCT concentration, in patients admitted to the intensive care unit (ICU) due to lung influenza infection.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Design</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Secondary analysis of a prospective multicentre observational study.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Setting</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">148 Spanish ICUs.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Patients</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">ICU patients admitted with influenza infection without bacterial co-infection. Clinical, laboratory and hemodynamic variables were recorded. AKI was classified as AKI I or II based on creatinine (Cr) concentrations (≥1.60–2.50<span class="elsevierStyleHsp" style=""></span>mg/dL and Cr<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>2.51–3.99<span class="elsevierStyleHsp" style=""></span>mg/dL, respectively). Patients with chronic renal disease, receiving renal replacement treatment or with Cr<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>mg/dL were excluded. Spearman's correlation, simple and multiple linear regression analysis were performed.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Interventions</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">None.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Out of 663 patients included in the study, 52 (8.2%) and 10 (1.6%) developed AKI I and II, respectively. Patients with AKI were significantly older, had more comorbid conditions and were more severally ill. PCT concentrations were higher in patients with AKI (2.62 [0.60–10.0]<span class="elsevierStyleHsp" style=""></span>ng/mL vs. 0.40 [0.13–1.20]<span class="elsevierStyleHsp" style=""></span>ng/mL, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.002). Weak correlations between Cr/PCT (rho<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.18) and Urea (U)/PCT (rho<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.19) were identified. Simple linear regression showed poor interaction between Cr/U and PCT concentrations (Cr <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03 and U <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.018). Similar results were observed during multiple linear regression analysis (Cr <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.046 and U <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.013).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Although PCT concentrations were slightly higher in patients with AKI, high PCT concentrations are not explained by AKI and could be warning sign of a potential bacterial infection.</p></span>" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Design" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Setting" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Patients" ] 5 => array:2 [ "identificador" => "abst0030" "titulo" => "Interventions" ] 6 => array:2 [ "identificador" => "abst0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Introducción</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Los niveles de procalcitonina (PCT) pueden elevarse en pacientes con disfunción renal aún en ausencia de infección bacteriana.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Objetivos</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Determinar la interacción entre los biomarcadores de disfunción renal aguda (AKI) y las concentraciones séricas de PCT en pacientes ingresados en cuidados intensivos (UCI) debido a infección por gripe.</p></span> <span id="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Diseño</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Análisis secundario de un estudio prospectivo, multicéntrico observacional.</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Lugar</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Ciento cuarenta y ocho UCI.</p></span> <span id="abst0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Pacientes</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Con infección por gripe sin co-infección bacteriana. Se registraron las variables clínicas, de laboratorio y hemodinámicas. El nivel de AKI fue definido como AKI I y II basado en la creatinina (Cr) sérica (<span class="elsevierStyleUnderline">></span><span class="elsevierStyleHsp" style=""></span>1,60-2,50<span class="elsevierStyleHsp" style=""></span>mg/dl y <span class="elsevierStyleUnderline">></span><span class="elsevierStyleHsp" style=""></span>2,51-3,99<span class="elsevierStyleHsp" style=""></span>mg/dl), respectivamente. Pacientes con insuficiencia renal crónica, técnicas de reemplazo renal o Cr<span class="elsevierStyleHsp" style=""></span>>4<span class="elsevierStyleHsp" style=""></span>mg/dl fueron excluidos. El análisis estadístico se realizó mediante correlación de Spearman y regresión linear simple y múltiple.</p></span> <span id="abst0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Intervenciones</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Ninguna.</p></span> <span id="abst0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Resultados</span><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">De los 663 pacientes incluidos, 52 (8,2%) y 10 (1,6%) desarrollaron AKI I y II, respectivamente. Pacientes con AKI fueron más añosos, presentaron más comorbilidades y mayor nivel de gravedad. Los niveles de PCT fueron mayores en pacientes con AKI (2,62 [0,60-10,0] ng/ml vs. 0,40 [0,13-1,20] ng/ml; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,002). Se observaron correlaciones débiles entre Cr/PCT (rho<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,18) y PCT/U (rho<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,19). La regresión linear simple evidenció una pobre contribución tanto de Cr (R<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,03) como de U (R<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,018) sobre los niveles de PCT. Resultados similares fueron obtenidos con la regresión linear múltiple para Cr (R<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,046) y U (R<span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,013).</p></span> <span id="abst0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusiones</span><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Aunque los valores de PCT pueden estar elevados en pacientes con AKI, altos niveles de PCT no pueden ser explicados por la disfunción renal y podrían ser un signo de alarma de una potencial infección bacteriana.</p></span>" "secciones" => array:8 [ 0 => array:2 [ "identificador" => "abst0045" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0050" "titulo" => "Objetivos" ] 2 => array:2 [ "identificador" => "abst0055" "titulo" => "Diseño" ] 3 => array:2 [ "identificador" => "abst0060" "titulo" => "Lugar" ] 4 => array:2 [ "identificador" => "abst0065" "titulo" => "Pacientes" ] 5 => array:2 [ "identificador" => "abst0070" "titulo" => "Intervenciones" ] 6 => array:2 [ "identificador" => "abst0075" "titulo" => "Resultados" ] 7 => array:2 [ "identificador" => "abst0080" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">GETGAG study Group investigators are listed in <a class="elsevierStyleCrossRef" href="#sec0110">Appendix 2</a>.</p>" "identificador" => "fn1" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0170" class="elsevierStylePara elsevierViewall"><elsevierMultimedia ident="upi0005"></elsevierMultimedia><elsevierMultimedia ident="upi0010"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0110" ] ] ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1863 "Ancho" => 2262 "Tamanyo" => 218945 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Flow chart of patients (PCT: procalcitonin; ICU: intensive care unit; CARC: community-acquired respiratory coinfection; CKD: chronic kidney disease; RRT: renal replacement techniques; AKI: acute kidney injury).</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2929 "Ancho" => 2514 "Tamanyo" => 256619 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">A/B: Boxplots showing the relationship between creatinine (A) and urea (B) levels according PCT cut-off.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2224 "Ancho" => 2919 "Tamanyo" => 361641 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Scatterplot of creatinine (<span class="elsevierStyleItalic">x</span> axis) vs. procalcitonin (PCT). Each point in the scatterplot represents the value of two variables for a given observation. The low rank Spearman correlation coefficient (rho<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.18) confirms that Cr and PCT are not correlated strongly.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 2127 "Ancho" => 2920 "Tamanyo" => 379188 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Scatterplot of urea (<span class="elsevierStyleItalic">x</span> axis) vs. procalcitonin (PCT). Each point in the scatterplot represents the value of two variables for a given observation. The low rank Spearman correlation coefficient (rho<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.19) confirms that urea and PCT are not correlated strongly.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AKI stage 0 (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>571) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AKI stage I (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>52) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">AKI stage II (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Demographics</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age (in years), median (25th–75th percentiles) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">48 (38–59) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">58 (51–66.7)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60 (51.2–69.7)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Gender (male), <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">316 (55.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31 (59.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (70) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Severity of illness</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>APACHE II, median (25th–75th percentiles) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (9–18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.5 (15.2–25)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29 (20.5–30.2)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Modified APACHE II, median (25th–75th percentiles) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (9–18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18.5 (14–23)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26 (18.5–28)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>SOFA, median (25th–75th percentiles) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (3–7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (6–10)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.5 (8–12)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Major comorbidities</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>COPD, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 (17.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (25.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (20) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic heart failure, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">44 (7.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (13.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (20) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Immunosuppresion, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52 (9.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (23.1)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (10) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Major complications</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Shock upon ICU admission, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">264 (46.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35 (67.3)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (100)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Need of mechanical ventilation upon ICU admission, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">444 (77.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42 (80.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (100) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Laboratory findings</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Serum creatinine upon ICU admission (mg/dL), median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.8 (0.6–1.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.7 (1.6–1.9)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.2 (2.8–3.4)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Serum urea upon ICU admission (mg/dL), median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">33 (23–45) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">73 (53–103) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">111.5 (79.5–136)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PCT upon ICU admission (ng/mL), median (25th–75th percentiles) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.40 (0.13–1.20) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.93 (0.6–10.9)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.40 (1.1–9.7)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>White cell counts (WCC) (10<span class="elsevierStyleSup">9</span>/L), median (25th–75th percentiles) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.9 (4.3–10.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.9 (5.8–15.8)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.0 (5.1–13.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"><span class="elsevierStyleItalic">Outcome</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ICU LOS,<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> median (25th–75th percentiles) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (4–18.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (4–18) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (5.5–16.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ICU mortality rate, <span class="elsevierStyleItalic">n</span> (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">93 (16.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (25.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (10) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1850332.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 for all comparisons with AKI 0 stage (reference group).</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">LOS: length of stay calculated only in survivors.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Characteristics of 633 patients included in the study according to renal function.</p>" ] ] 5 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Regression statistics \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Creatinine</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Urea</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">With outliers \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Without outliers \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Only outliers \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">With outliers \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Without outliers \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Only outliers \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Correlation coefficient (<span class="elsevierStyleItalic">r</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.008 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.18 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">R</span>-squared (<span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span>) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.000 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.006 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.018 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Adjusted <span class="elsevierStyleItalic">R</span><span class="elsevierStyleSup">2</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.016 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Standard deviation (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"><span class="elsevierStyleItalic">Regression parameters</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Intercept (SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.592 (−2.29 to 1.10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.456 (0.17–0.73) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30.0 (13.6–46.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.798 (0.36–3.22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.717 (0.49–0.93) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28.7 (11.5–46.0) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Slope \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.844 (2.22–5.46) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.61 (0.34–0.89) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.28 (−11.0 to 10.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.029 (0.001–0.57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.007 (0.003–0.012) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.018 (−0.28 to 0.32) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1850333.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Results based on correlation and simple linear regression analysis for creatinine and urea considering procalcitonin (PCT) as dependent variable.</p>" ] ] 6 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 197790 ] ] 7 => array:5 [ "identificador" => "upi0010" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc2.pdf" "ficheroTamanyo" => 111983 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biomarkers in respiratory tract infections: diagnostic guides to antibiotic prescription, prognostic markers and mediators" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M. 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| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Octubre | 101 | 59 | 160 |
| 2024 Septiembre | 99 | 55 | 154 |
| 2024 Agosto | 102 | 66 | 168 |
| 2024 Julio | 65 | 36 | 101 |
| 2024 Junio | 121 | 97 | 218 |
| 2024 Mayo | 85 | 42 | 127 |
| 2024 Abril | 92 | 53 | 145 |
| 2024 Marzo | 104 | 34 | 138 |
| 2024 Febrero | 92 | 47 | 139 |
| 2024 Enero | 86 | 33 | 119 |
| 2023 Diciembre | 83 | 47 | 130 |
| 2023 Noviembre | 83 | 44 | 127 |
| 2023 Octubre | 88 | 42 | 130 |
| 2023 Septiembre | 49 | 43 | 92 |
| 2023 Agosto | 45 | 17 | 62 |
| 2023 Julio | 55 | 33 | 88 |
| 2023 Junio | 59 | 28 | 87 |
| 2023 Mayo | 79 | 33 | 112 |
| 2023 Abril | 66 | 35 | 101 |
| 2023 Marzo | 128 | 48 | 176 |
| 2023 Febrero | 152 | 34 | 186 |
| 2023 Enero | 103 | 26 | 129 |
| 2022 Diciembre | 116 | 53 | 169 |
| 2022 Noviembre | 78 | 63 | 141 |
| 2022 Octubre | 75 | 39 | 114 |
| 2022 Septiembre | 82 | 44 | 126 |
| 2022 Agosto | 64 | 54 | 118 |
| 2022 Julio | 74 | 42 | 116 |
| 2022 Junio | 64 | 44 | 108 |
| 2022 Mayo | 114 | 48 | 162 |
| 2022 Abril | 144 | 44 | 188 |
| 2022 Marzo | 178 | 67 | 245 |
| 2022 Febrero | 196 | 45 | 241 |
| 2022 Enero | 183 | 47 | 230 |
| 2021 Diciembre | 92 | 61 | 153 |
| 2021 Noviembre | 118 | 57 | 175 |
| 2021 Octubre | 95 | 63 | 158 |
| 2021 Septiembre | 55 | 27 | 82 |
| 2021 Agosto | 77 | 48 | 125 |
| 2021 Julio | 63 | 39 | 102 |
| 2021 Junio | 73 | 43 | 116 |
| 2021 Mayo | 100 | 76 | 176 |
| 2021 Abril | 197 | 164 | 361 |
| 2021 Marzo | 129 | 34 | 163 |
| 2021 Febrero | 165 | 32 | 197 |
| 2021 Enero | 143 | 40 | 183 |
| 2020 Diciembre | 122 | 31 | 153 |
| 2020 Noviembre | 125 | 26 | 151 |
| 2020 Octubre | 91 | 33 | 124 |
| 2020 Septiembre | 96 | 35 | 131 |
| 2020 Agosto | 63 | 21 | 84 |
| 2020 Julio | 95 | 29 | 124 |
| 2020 Junio | 91 | 43 | 134 |
| 2020 Mayo | 61 | 29 | 90 |
| 2020 Abril | 95 | 33 | 128 |
| 2020 Marzo | 54 | 16 | 70 |
| 2020 Febrero | 150 | 45 | 195 |
| 2020 Enero | 70 | 45 | 115 |
| 2019 Diciembre | 92 | 21 | 113 |
| 2019 Noviembre | 95 | 19 | 114 |
| 2019 Octubre | 82 | 24 | 106 |
| 2019 Septiembre | 61 | 29 | 90 |
| 2019 Agosto | 49 | 29 | 78 |
| 2019 Julio | 62 | 37 | 99 |
| 2019 Junio | 61 | 30 | 91 |
| 2019 Mayo | 78 | 51 | 129 |
| 2019 Abril | 56 | 27 | 83 |
| 2019 Marzo | 62 | 39 | 101 |
| 2019 Febrero | 54 | 54 | 108 |
| 2019 Enero | 39 | 33 | 72 |
| 2018 Diciembre | 2 | 6 | 8 |
| 2018 Noviembre | 2 | 2 | 4 |
| 2018 Octubre | 28 | 15 | 43 |
| 2018 Septiembre | 15 | 4 | 19 |
| 2018 Julio | 0 | 1 | 1 |
| 2018 Junio | 0 | 1 | 1 |
| 2018 Febrero | 0 | 4 | 4 |
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