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

Fig. 1. Flow chart of study design and data analysis. AKI acute kidney injury, KRT kidney replacement therapy, CKRT continuous veno-venous hemodiafiltration, SLED sustained low-efficiency dialysis (Genius-System), IHD including intermittent hemodialysis, acute KRT patients with acute need for KRT during ICU stay, pre-existing chronic KRT patients with KRT dependency prior ICU admission. 1Data available at KRT start, 2data available at the time of KRT liberation, αchronic KRT patients with continuous PENK values eligible for comparison with acute KRT patients.

Fig. 2. Maximum PENK (A) and SCr levels (B) stratified by AKI stage within 7 days of admission. AKI acute kidney injury, PENK proenkephalin, KRT kidney replacement therapy, SCr serum creatinine. Gray lines indicate upper normal range. Statistical significance is indicated as follows: ns, P ≥ 0.05; P < 0.05 (*); P < 0.01 (**); P < 0.001 (***); P < 0.0001 (****).

Fig. 3. PENK and SCr levels stratified by KRT modality and acute versus chronic KRT. A + B timely matched course of PENK and SCr in relation to the start of kidney replacement therapy stratified by KRT modalities. C + D timely matched course of PENK and SCr in relation to start of kidney replacement therapy stratified comparing acute KRT versus pre-existing chronic KRT (N = 138). CKRT continuous kidney replacement therapy, IHD intermittent hemodialysis, PENK proenkephalin, KRT kidney replacement therapy, SCr serum creatinine, SLED sustained low-efficiency dialysis (Genius). Gray lines indicate upper normal range. Statistical significance is indicated as follows: ns, P ≥ 0.05; P < 0.05 (*); P < 0.01 (**); P < 0.001 (***); P < 0.0001 (****).

Fig. 4. Biomarker kinetics and receiver-operating characteristic (ROC) analysis of PENK to differentiate liberation failure (N = 33) from KRT liberation success (N = 37) in comparison to SCr and 24 h urine output (N = 70). AUC area under the curve, PENK proenkephalin, KRT kidney replacement therapy, SCr serum creatinine. Gray lines indicate upper normal range. Statistical significance is indicated as follows: ns, P ≥ 0.05; P < 0.05 (*); P < 0.01 (**); P < 0.001 (***); P < 0.0001 (****).

Fig. 5. Decision tree integrating 24-h urine output (UO) and PENK for prediction of CKRT liberation outcomes (N = 70). Patients were first stratified by UO ≥ 500 mL/24 h or <500 mL/24 h, followed by PENK categories (<89 pmol/L, 89–249 pmol/L, ≥250 pmol/L). Failure and success rates of liberation trials are shown for each subgroup. KRT kidney replacement therapy, PENK proenkephalin, UO urine output.