Proenkephalin A for assessing kidney integrity and guiding KRT liberation decisions in critically ill patients.

BACKGROUND: Utility of serum creatinine (SCr) and urine output (UO) is limited for real-time assessments of functional integrity and guiding kidney replacement therapy (KRT) decisions in acute kidney injury (AKI). Proenkephalin A 119-159 (PENK) may overcome these limitations. We evaluate PENK's use for AKI staging, assessment of residual kidney function during KRT, and assessment of liberation failure. METHODS: Prospective, real-world study in 1,436 critically ill patients at Heidelberg University Hospital, including a subgroup of 138 patients receiving KRT for liberation analyses. Plasma PENK was measured from admission to discharge. AKI was defined by KDIGO criteria; biomarker kinetic, ROC analyses and binary logistic regression models were performed. KRT liberation was considered successful if no re-initiation occurred within >5 days. RESULTS: Of 1,436 patients, 621 (43.2%) developed AKI. Acute KRT was required in 12.6%, 40.9% of whom were successfully liberated, 24.3% failed, and 31.5% underwent no liberation attempt (3.3% lost to follow up). PENK rose with AKI stages and, unlike SCr/UO, distinguished stage 3 AKI with versus without acute KRT requirements, and differentiated acute from chronic KRT patients even under ongoing KRT. From KRT start, mean PENK levels increased progressively whereas SCr decreased under treatment. Later, PENK declined around successful liberation, with lower values compared to cases with liberation failure. PENK was the strongest, independent predictor of KRT liberation failure, outperforming SCr. A PENK cut-off of ≥250 pmol/L provided >90% specificity for liberation failure. Combining PENK and UO, further improved risk stratification. CONCLUSIONS: PENK may reflect kidney integrity independent of KRT, enhance residual kidney function assessment, and may aid prediction of KRT liberation failure, warranting multicenter validation.