Proenkephalin Predicts Organ Failure, Renal Replacement Therapy, and Mortality in Patients With Sepsis

Abstract

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 m 2 ), 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.

Mortality among adult patients with sepsis and septic shock in Korea: a systematic review and meta-analysis

“…The 28- or 30-day mortality from sepsis diagnosed using the Sepsis-3 criteria was 22.7% (95% confidence interval [CI], 20.0%–25.6%; I 2 =89%) ( Table 2 and Fig. 2 ) [ 15 , 17 , 21 , 26 , 27 , 35 , 39 , 42 , 46 , 50 , 55 – 59 , 69 , 72 ]. The range of mortality in the included studies was 14.4% to 40.8%.…”

“…In addition, the 28- or 30-day mortality rate by including all sepsis criteria was 24.8% (95% CI, 22.1%–27.7%; I 2 =95%) ( Supplementary Fig. 1 ) [ 15 , 17 , 20 , 21 , 26 , 27 , 29 – 31 , 34 , 35 , 39 , 42 , 44 , 46 , 50 , 55 – 59 , 63 , 69 , 71 , 72 , 74 ]. In the subgroup analyses, 28- or 30-day mortality from sepsis was 22.6% (95% CI, 19.5%–25.9%; I 2 =94%) in retrospective cohort studies, 29.1% (95% CI, 23.4%–35.5%; I 2 =96%) in prospective studies, 23.3% (95% CI, 20.5%–26.5%; I 2 =93%) in single-center studies, and 31.3% (95% CI, 23.4%–40.4%; I 2 =98%) in multicenter studies ( Table 2 ).…”

Reference Interval for the Axis-Shield Clinical Chemistry Heparin-Binding Protein Assay

“…This result implies that HBP concentration may be high without sepsis or other known ill conditions. Several biomarkers, including biologically active adrenomedullin and proenkephalin, have been reported that could be objective and useful markers to predict severity, organ failure, and mortality in septic patients [ 29 , 30 ]. Since the concentration of these biomarkers vary among individuals, it is mandatory to understand the biological variation (BV) of a biomarker in healthy individuals [ 31 , 32 ].…”

Predictive value of blood pressure variability for organ dysfunction in patients with sepsis

“…The higher the level of these indicators, the more serious the sepsis. Multiple organ failure and persistent organ failure are among the most important risk factors for poor prognosis (17)(18)(19), and 28-day mortality is the most important prognosis index. Combined with the results of this study, BPV has a substantial value in predicting the prognosis of patients with sepsis, which is closely related to the severity of sepsis, and it is worthy of further study.…”