Background: Kidney failure occurs frequently and is associated with high mortality during sepsis. Proenkephalin (PENK) is an emerging biomarker of kidney function. We explored whether PENK levels could predict severity, organ failure, and mortality in septic patients. Methods: We measured the PENK level in the plasma of 215 septic patients using the sphingotest penKid assay (Sphingotec GmbH, Hennigsdorf, Germany). This was analyzed in terms of sepsis severity, vasopressor use, 30-day mortality, sequential organ failure assessment (SOFA) renal subscore, the Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (CKD-EPI eGFR) categories, and renal replacement therapy (RRT) requirement. Results: The PENK levels were significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (P = 0.02, P = 0.007, P < 0.001, respectively). The PENK levels were significantly associated with SOFA renal subscore and CKD-EPI eGFR categories (both P < 0.001). The distribution of lower eGFR ( < 60 mL/min/1.73 m2 ), RRT requirement, SOFA renal subscore, and the number of organ failures differed significantly according to the PENK quartile (P for trend < 0.001 or 0.017). The 30-day mortality rate also differed significantly according to the PENK quartile (P for trend < 0.001). Conclusions PENK could be an objective and reliable marker to predict severity, organ failure, and 30-day mortality in septic patients.

BACKGROUND: Proenkephalin (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. METHODS: A 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-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. RESULTS: The 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. CONCLUSIONS: PENK 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.
Acute Kidney Injury ; Cooperative Behavior ; Critical Care ; Diet ; Epidemiology ; Glomerular Filtration Rate* ; Humans ; Inflammation ; Kidney ; Lipocalins* ; Mass Spectrometry ; Mortality ; Neutrophils* ; Plasma ; Prognosis ; Renal Insufficiency, Chronic ; Renal Replacement Therapy ; Sepsis* ; Shock, Septic