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Proenkephalin A levels show no correlation with kidney or cardiac markers in hemodialysis patients

Proenkephalin A levels show no correlation with kidney or cardiac markers in hemodialysis patients
Photo by Europeana / Unsplash
Key Takeaway
Interpret PENK biomarker findings cautiously in ESKD due to lack of correlation with standard markers.

This prospective cohort study enrolled 100 adult patients with end-stage kidney disease (ESKD) undergoing maintenance hemodialysis at a single center. The intervention involved measuring Proenkephalin A 119–159 (PENK) levels before and after a single hemodialysis session, with comparisons to estimated GFR (eGFR), BUN, SCr, NT-proBNP, and LVEF. The primary outcome assessed correlations between PENK and eGFR, as well as PENK clearance during hemodialysis.

Main results showed no significant correlations between PENK and eGFR (r = -0.00, p = 0.99), BUN (r = 0.16, p = 0.10), SCr (r = 0.18, p = 0.08), NT-proBNP (r = -0.06, p = 0.58), or LVEF (r = 0.12, p = 0.26) in the entire cohort. In a subgroup of 56 patients with residual urine output, PENK and eGFR also showed no significant correlation (r = -0.15, p = 0.28). BUN clearance during hemodialysis was significant (12.59 vs. 3.68 mmol/L, p < 0.05), but PENK clearance data were not reported.

Safety and tolerability were not reported. Key limitations include the single-center design and lack of reported funding or conflicts. The study notes associations only, with no causation claimed, and the clinical utility of PENK in ESKD remains to be established. Practice relevance is not reported, and findings should be interpreted cautiously due to the observational nature and limited generalizability.

Study Details

Study typeCohort
EvidenceLevel 3
PublishedApr 2026
View Original Abstract ↓
BackgroundHigh levels of Proenkephalin A 119–159 (PENK) have been associated with decreased glomerular filtration rate (GFR) in subjects with preserved kidney function, yet its clinical utility in patients with end-stage kidney disease (ESKD) remains to be established. This study aimed to investigate the correlation between PENK and GFR, and evaluate the clearance of PENK during hemodialysis (HD) in ESKD patients.MethodsThis single-center prospective cohort study enrolled adult patients with ESKD undergoing maintenance HD. Plasma PENK levels were determined before (baseline) and after a single HD session using a double-antibody sandwich enzyme-linked immunosorbent assay. The associations of PENK with estimated GFR (eGFR), and other markers of kidney function and heart failure were analyzed at baseline. Furthermore, changes in PENK levels during HD were evaluated to assess its dialytic clearance.ResultsA total of 100 ESKD patients were enrolled. At baseline, the median eGFR and PENK level were 6.30 mL/min/1.73 m2 and 4.88 ng/mL, respectively. In the entire cohort (n = 100), no significant correlations were observed between PENK and eGFR (r = −0.00, p = 0.99), BUN (r = 0.16, p = 0.10), SCr (r = 0.18, p = 0.08), NT-proBNP (r = −0.06, p = 0.58), or LVEF (r = 0.12, p = 0.26). Among patients with residual urine output (n = 56), PENK and eGFR also exhibited no significant correlation (r = −0.15, p = 0.28). Although significant clearance was observed for BUN (12.59 vs. 3.68 mmol/L, p 
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