Proenkephalin (PENK): a functional biomarker in chronic kidney diseases - hope or just a new bystander?

Proenkephalin has recently emerged as a promising biomarker of kidney function which improves the early detection of acute kidney injury (AKI) compared to creatinine-based methods. Plasma Proenkephalin concentrations have shown a correlation with glomerular filtration rate (GFR) as assessed by gold standard methods. Previous studies have demonstrated its association with adverse clinical outcomes in various settings, including sepsis, heart failure, kidney transplantation, and chronic kidney disease (CKD). Additionally, in healthy individuals, elevated Proenkephalin concentrations have been linked to a decline in GFR and an increased risk of developing CKD. While evidence suggests that Proenkephalin may be a more accurate tool for assessing glomerular filtration and detecting AKI, recent research has primarily focused on subjects with preserved kidney function, leaving its value in CKD patients less explored. Given the heterogeneity and high risk of rapid renal deterioration in patients with chronically impaired kidney function, a reliable biomarker should retain its ability to reflect kidney function in both CKD and AKI settings. This review summarizes the current evidence on Proenkephalin in patients with chronic kidney diseases.