Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study

Abstract

IntroductionSepsis is the leading cause of acute kidney injury (AKI) in critically ill patients. The Kidney in Sepsis and Septic Shock (Kid-SSS) study evaluated the value of proenkephalin A 119-159 (penkid)—a sensitive biomarker of glomerular function, drawn within 24 hours upon intensive care unit (ICU) admission and analyzed using a chemiluminescence immunoassay—for kidney events in sepsis and septic shock.MethodsThe Kid-SSS study was a substudy of Adrenomedullin and Outcome in Severe Sepsis and Septic Shock (AdrenOSS) (NCT02393781), a prospective, observational, multinational study including 583 patients admitted to the intensive care unit with sepsis or septic shock and a validation cohort of 525 patients from the French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study. The primary endpoint was major adverse kidney events (MAKEs) at day 7, composite of death, renal replacement therapy, and persistent renal dysfunction. The secondary endpoints included AKI, transient AKI, worsening renal function (WRF), and 28-day mortality.ResultsMedian age was 66 years (interquartile range 55–75), and 28-day mortality was 22% (95% confidence interval [CI] 19%−25%). Of the patients, 293 (50.3%) were in shock upon ICU admission. Penkid was significantly elevated in patients with MAKEs, persistent AKI, and WRF (median = 65 [IQR = 45–106] vs. 179 [114–242]; 53 [39–70] vs. 133 [79–196] pmol/l; and 70 [47–121] vs. 174 [93–242] pmol/l, all P < 0.0001), also after adjustment for confounding factors (adjusted odds ratio = 3.3 [95% CI = 1.8–6.0], 3.9 [95% CI = 2.1–7.2], and 3.4 [95% CI = 1.9–6.2], all P < 0.0001). Penkid increase preceded elevation of serum creatinine with WRF and was low in renal recovery.ConclusionAdmission penkid concentration was associated with MAKEs, AKI, and WRF in a timely manner in septic patients.

Proenkephalin A 119-159 (penKid) – a novel biomarker for acute kidney injury in sepsis: An observational study.

“…On the other hand, a high value of penKid seems to represent a more important state of risk than a low value of eGFR, as penKid predicted 28-day mortality, whereas eGFR did not. This is in line with several previous studies (11,(15)(16)(17).…”

“…Similar rates of AKI incidence and mortality are presented in a recent study on septic AKI in the unselected ED setting(11), while others have shown slightly higher rates of mortality and AKI in recent publications, but these studies were carried out in the critical care setting, studying patients after ICU-admission. (15,16) The current definition of AKI, both with and without presence of sepsis, is based on the KDIGO-or RIFLE-criteria, which include SCr and urine output. These markers have been mainstays in previous iterations of septic AKI definitions.…”

“…The cohort characteristics, especially regarding mortality and AKI incidence, are comparable to that of a pilot study (11) in the field of penKid prediction of AKI in sepsis. Relative to other papers studying penKid in septic AKI (15,16), the cohort in this study could be deemed rather healthy given the fewer number of ICUadmissions and instances of RRT. It needs to be stressed, however, that these other studies were conducted in the critical care setting, following patients after ICU-admission, whereas the current study population is representative of the patients meeting the emergency physician upon immediate admission to the ED.…”

“…(9) PenKid has been shown to independently predict a variety of significant conditions related to increased morbidity and mortality, such as incidence of chronic kidney disease in the general population (10), worsening renal function and need for renal replacement therapy (RRT) (11), worsening renal function in acute and congestive heart failure (12) and AKI as a complication to cardiac surgery (13,14). In recent studies on septic patients in the intensive care unit (ICU) setting (15)(16)(17), it has been shown that penKid is a highly specific biomarker for renal function and associated with AKI. Also, in contrast to other novel biomarkers for AKI prediction, it has been shown that penKid remains highly specific for renal function despite massive inflammatory drive, as concentrations remain low in the absence of renal dysfunction in the septic patient.…”

Proenkephalin as a new biomarker for pediatric acute kidney injury – reference values and performance in children under one year of age

“…Research in healthy and diseased adults supports PENK as an early indicator of AKI and independent predictor of impaired kidney function. Moreover, PENK was strongly correlated with estimated and measured GFR after cardiac surgery and in septic patients [20][21][22][23][24][25][26][27][28][29].…”