NephroPOC – Proenkephalin A 119-159 predicts acute kidney injury and 28-day mortality in patients with suspected organ dysfunction in the emergency department (ED): secondary analysis from the prospective observational LifePOC study

Abstract

Background: Volume depletion, sepsis, major surgery, and nephrotoxins are the most common causes of acute kidney injury (AKI). The classical markers serum creatinine (Scr) and urine output (UO) for the evaluation of kidney function are of limited value in critical ill patients because they reflect an already existing organ dysfunction. Our hypothesis is that the measurement of the functional biomarker Proenkephalin A 119-159 (penKid), which is freely filtered in the glomerulus and is used as a marker for estimating the glomerular filtration rate, contributes to the early identification of patients with subclinical kidney damage. Methods: This was a secondary analysis of the prospective multicenter LifePOC study. We evaluated critically ill patients admitted to the emergency department (ED) with suspected organ dysfunction based on the risk-stratification tool qSOFA , who developed AKI, defined as Scr ≥0.3 mg/dl from baseline, within 72 hours of enrolment. The primary endpoint was evolving AKI after 48 h. AKI after 24 h, AKI after 72 h and 28-day mortality were defined as secondary endpoints. Measurement and main results: Within 48 h, 88 out of 453 patients (19.4%) developed AKI. Patients with AKI showed increased penKid levels at admission in comparison to patients without AKI (111.5 [73.0-247.5] pmol/l vs. 74.8 [47.2-120.4] pmol/l, p<0.001). PenKid was a superior predictor for AKI within 24, 48 and 72 h in comparison to Scr (all p<0.05), and the advantage increased the later the renal events occurred. Regarding 28-day mortality prediction, penKid also outperformed Scr (p<0.05). The observed superiority of penKid persisted if the recently proposed PENK-Crea formula to estimate the GFR was applied and compared to the latest CKD-EPI formula. Conclusions: Early measurement and the trajectory of penKid predicts early AKI and 28-day mortality in patients with suspected organ dysfunction in the ED superior compared to the classical marker Scr. The results indicate that the superiority is attributed to an earlier rise in penKid compared to Scr. Trial registration: The trial was registered in the German Registry for Clinical Trials (DRKS00011188) on 20 October 2016.