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Kidney Week

Abstract: TH-PO0698

Proenkephalin Predicts Severe AKI in High-Risk Patients

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

  • Koyner, Jay L., The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Fatima, Aiman, The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Anjorin, Ola, The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Zisman, Anna L., The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Gunning, Samantha, The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Puri, Tipu S., The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Prochaska, Megan, The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States
  • Ko, Benjamin S., The University of Chicago Division of the Biological Sciences, Chicago, Illinois, United States

Group or Team Name

  • ESTOP Investigators
Background

Proenkephalin A 119–159 (penKid) has shown promise as a biomarker for early detection of AKI in the ICU. However, further validation of PenKid in and out of the ICU is needed.

Methods

We conducted a post-hoc analysis of the ESTOP-AKI randomized controlled trial (RCT). In this RCT, ward and ICU patients without KDIGO SCr-based AKI but at increased risk for severe (stage 2 and higher) AKI, as measured by a machine-learning risk score (≥0.01), were randomized to an early nephrology consult or usual care. Blood and urine samples from enrolled patients (180) were collected at days 1 and 2 after admission and biobanked. Penkid was measured using a chemiluminescence immunoassay (SphingoTec GmbH, Hennigsdorf, Germany). The area under the curve (AUC) for Penkid to predict KDIGO AKI severity, including persistent AKI lasting ≥48 hours, and other outcomes was examined.

Results

PenKid was measured in 167 patients with a mean age of 62.5 years, 54.5% were male. KDIGO AKI occurred in 65 (39%) in the 7 days after enrollment, with 25 patients (15%) having severe AKI (≥ stage 2), and 11 (7%) had persistent severe AKI. 4 (2.4%) patients received RRT and 14 (8%) died during their admission. The mean pre-hospital baseline SCr (mg/dL) was 0.91, with a SCr of 1.06 at enrollment and 1.03 at day 1. The table provides the AUC (standard error) for penKid values over the first 2 study days to predict the development of AKI, severe AKI, persistent severe AKI, and RRT within next 7 days, as well as inpatient mortality in all patients and those in the ICU (n=92, 55%). A Penkid cutoff of 89 pmol/l had a sensitivity for 25% and a specificity of 91% for receipt of RRT and 25% and 92% for the prediction of persistent severe AKI.

Conclusion

In a cohort already enriched to be at increased risk for severe AKI, penKid measured within 36 hours of elevated ESTOP risk score reliably identifies hospitalized patients (especially in the ICU) at the highest risk for persistent stage ≥2 AKI (AUC 0.78) and RRT (AUC 0.90)

Acknowledgment

We wish to thank Sphingotec for the measurement of PenKid

Performance of PenKid
AUC(SE)
*P<0.05
All AKISevere AKIPersistent Severe AKIRRTInpatient Mortality
Whole Cohort (n=167)n=65n=26n=11n=4n=14
PenKid Day 10.61 (0.05)*0.64 (0.07)0.61 (0.11)*0.79 (0.13)0.51 (0.10)
PenKid Day 20.61 (0.05)*0.66(0.08)*0.76 (0.10)*0.85 (0.06)*0.53 (0.10)
ICU cohort (N=92)n=50n=20n=9n=4n=12
PenKid Day 10.67 (0.07)*0.65 (0.08)0.61 (0.12)0.81 (0.19)0.46 (0.12)
PenKid Day 20.63 (0.07)0.67 (0.08)*0.78 (0.10)*0.90 (0.05)*0.52 (0.11)

Funding

  • NIDDK Support