IntroductionThe incidence of death among patients admitted for severe sepsis or septic shock is high. Adrenomedullin (ADM) plays a central role in initiating the hyperdynamic response during the early stages of sepsis. Pilot studies indicate an association of plasma ADM with the severity of the disease. In the present study we utilized a novel sandwich immunoassay of bioactive plasma ADM in patients hospitalized with sepsis in order to assess the clinical utility.MethodsWe enrolled 101 consecutive patients admitted to the emergency department with suspected sepsis in this study. Sepsis was defined by fulfillment of at least two systemic inflammatory response syndrome (SIRS) criteria plus clinical suspicion of infection. Plasma samples for ADM measurement were obtained on admission and for the next four days. The 28-day mortality rate was recorded.ResultsADM at admission was associated with severity of disease (correlation with Acute Physiology and Chronic Health Evaluation II (APACHE II) score: r = 0.46; P <0.0001). ADM was also associated with 28-day mortality (ADM median (IQR): survivors: 50 (31 to 77) pg/mL; non-survivors: 84 (48 to 232) pg/mL; P <0.001) and was independent from and additive to APACHE II (P = 0.02). Cox regression analysis revealed an additive value of serial measurement of ADM over baseline assessment for prediction of 28-day mortality (P < 0.01). ADM was negatively correlated with mean arterial pressure (r = -0.39; P <0.0001), and it strongly discriminated those patients requiring vasopressor therapy from the others (ADM median (IQR): no vasopressors 48 (32 to 75) pg/mL; with vasopressors 129 (83 to 264) pg/mL, P <0.0001).ConclusionsIn patients admitted with sepsis, severe sepsis or septic shock plasma ADM is strongly associated with severity of disease, vasopressor requirement and 28-day mortality.

Use of pro-ENK in septic patients can detect the presence and severity of AKI. Moreover, pro-ENK is highly predictive of short-term mortality and could enable early identification of patients at risk of death.

The CREATE-ECLA Randomized Controlled TrialThe CREATE-ECLA Trial Group Investigators* See also pp 427 and 489.

IntroductionAcute kidney injury (AKI) is a common complication among hospitalized patients. The aim of this study was to evaluate the utility of blood neutrophil gelatinase-associated lipocalin (NGAL) assessment as an aid in the early risk evaluation for AKI development in admitted patients.MethodsThis is a multicenter Italian prospective emergency department (ED) cohort study in which we enrolled 665 patients admitted to hospital from the ED.ResultsBlood NGAL and serum creatinine (sCr) were determined at ED presentation (T0), and at: 6 (T6), 12 (T12), 24 (T24) and 72 (T72) hours after hospitalization. A preliminary assessment of AKI by the treating ED physician occurred in 218 out of 665 patients (33%), while RIFLE AKI by expert nephrologists was confirmed in 49 out of 665 patients (7%). The ED physician's initial judgement lacked sensitivity and specificity, overpredicting the diagnosis of AKI in 27% of the cohort, while missing 20% of those with AKI as a final diagnosis.The area under the receiver operating characteristic curve (AUC), obtained at T0, for blood NGAL alone in the AKI group was 0.80. When NGAL at T0 was added to the ED physician's initial clinical judgment the AUC was increased to 0.90, significantly greater when compared to the AUC of the T0 estimated glomerular filtration rate (eGFR) obtained either by modification of diet in renal disease (MDRD) equation (0.78) or Cockroft-Gault formula (0.78) (P = 0.022 and P = 0.020 respectively). The model obtained by combining NGAL with the ED physician's initial clinical judgement compared to the model combining sCr with the ED physician's initial clinical judgement, resulted in a net reclassification index of 32.4 percentage points. Serial assessment of T0 and T6 hours NGAL provided a high negative predictive value (NPV) (98%) in ruling out the diagnosis of AKI within 6 hours of patients' ED arrival. NGAL (T0) showed the strongest predictive value for in-hospital patient's mortality at a cutoff of 400 ng/ml.ConclusionsOur study demonstrated that assessment of a patient's initial blood NGAL when admitted to hospital from the ED improved the initial clinical diagnosis of AKI and predicted in-hospital mortality. Blood NGAL assessment coupled with the ED physician's clinical judgment may prove useful in deciding the appropriate strategies for patients at risk for the development of AKI.See related commentary by Legrand et al., http://ccforum.com/content/17/2/132

BackgroundProenkephalin (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.MethodsA 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.ResultsThe 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.ConclusionsPENK 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.