Rossella Marino1, Joachim Struck2, Oliver Hartmann3, Alan S Maisel4, Miriam Rehfeldt3, Laura Magrini1, Olle Melander5, Andreas Bergmann3, Salvatore Di Somma6. 1. Department of Medical Sciences and Translational Medicine, University of Rome Sapienza, Emergency Department Sant'Andrea Hospital, Via di Grottarossa 1035/1039, 00189, Rome, Italy. 2. Sphingotec GmbH, Hennigsdorf, Germany. struck@sphingotec.de. 3. Sphingotec GmbH, Hennigsdorf, Germany. 4. Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. 5. Department of Clinical Sciences, Lund University, Malmö, Sweden. 6. Department of Medical Sciences and Translational Medicine, University of Rome Sapienza, Emergency Department Sant'Andrea Hospital, Via di Grottarossa 1035/1039, 00189, Rome, Italy. salvatore.disomma@uniroma1.it.
Abstract
BACKGROUND: Acute kidney injury (AKI) aggravates the prognosis of patients with sepsis. Reliable biomarkers for early detection of AKI in this setting are lacking. Enkephalins influence kidney function, and may have a role in AKI from sepsis. We utilized a novel immunoassay for plasma proenkephalin (pro-ENK), a stable surrogate marker for endogenous enkephalins, in patients hospitalized with sepsis, in order to assess its clinical utility. METHODS: In an observational retrospective study we enrolled 101 consecutive patients admitted to the emergency department (ED) with suspected sepsis. Plasma levels of pro-ENK and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated at ED arrival for their association with presence and severity of AKI and 7-day mortality. RESULTS: pro-ENK was inversely correlated to creatinine clearance (r = -0.72) and increased with severity of AKI as determined by RIFLE (risk, injury, failure, loss of function, end-stage renal disease) stages (p < 0.0001; pro-ENK median [interquartile range, IQR]) pmol/l: no AKI: 71 [41-97]; risk: 72 [51-120]; injury: 200 [104-259]; failure: 230 [104-670]; loss of function: 947 [273-811]. The majority of septic patients without AKI or at risk had pro-ENK concentrations within the normal range. While NGAL was similarly associated with AKI severity, it was strongly elevated already in septic patients without AKI. pro-ENK added predictive information to NGAL for detecting kidney dysfunction (added χ (2) 10.0, p = 0.0016). Admission pro-ENK outperformed creatinine clearance in predicting 7-day mortality (pro-ENK: χ (2) 13.4, p < 0.001, area under curve, AUC 0.69; creatinine clearance: χ (2) 4, p = 0.045, AUC: 0.61), and serial measurement improved prediction. CONCLUSIONS: 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.
BACKGROUND:Acute kidney injury (AKI) aggravates the prognosis of patients with sepsis. Reliable biomarkers for early detection of AKI in this setting are lacking. Enkephalins influence kidney function, and may have a role in AKI from sepsis. We utilized a novel immunoassay for plasma proenkephalin (pro-ENK), a stable surrogate marker for endogenous enkephalins, in patients hospitalized with sepsis, in order to assess its clinical utility. METHODS: In an observational retrospective study we enrolled 101 consecutive patients admitted to the emergency department (ED) with suspected sepsis. Plasma levels of pro-ENK and neutrophil gelatinase-associated lipocalin (NGAL) were evaluated at ED arrival for their association with presence and severity of AKI and 7-day mortality. RESULTS:pro-ENK was inversely correlated to creatinine clearance (r = -0.72) and increased with severity of AKI as determined by RIFLE (risk, injury, failure, loss of function, end-stage renal disease) stages (p < 0.0001; pro-ENK median [interquartile range, IQR]) pmol/l: no AKI: 71 [41-97]; risk: 72 [51-120]; injury: 200 [104-259]; failure: 230 [104-670]; loss of function: 947 [273-811]. The majority of septic patients without AKI or at risk had pro-ENK concentrations within the normal range. While NGAL was similarly associated with AKI severity, it was strongly elevated already in septic patients without AKI. pro-ENK added predictive information to NGAL for detecting kidney dysfunction (added χ (2) 10.0, p = 0.0016). Admission pro-ENK outperformed creatinine clearance in predicting 7-day mortality (pro-ENK: χ (2) 13.4, p < 0.001, area under curve, AUC 0.69; creatinine clearance: χ (2) 4, p = 0.045, AUC: 0.61), and serial measurement improved prediction. CONCLUSIONS: 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.
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