Proenkephalin A 119-159 for Evaluating Glomerular Filtration Rate and Hemodialysis Adequacy in Patients with End-Stage Kidney Disease: A Prospective Cohort Study

Background: High 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. Methods: This 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. Results: A 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 < 0.001) and SCr (458.70 vs. 165.85 μmol/L, p < 0.001), PENK levels remained unchanged during HD (4.88 vs. 4.80 ng/mL, p = 0.85), with the stability unaffected by residual urine output, dialysis vintage, dialysis frequency, or comorbidities. Conclusion: In this cohort of ESKD patients, plasma PENK levels showed no significant correlation with eGFR, and negligible clearance of PENK was observed during HD. These preliminary results suggested limited value of PENK for evaluating residual kidney function and dialysis adequacy in patients with ESKD. Further studies are required to clarify the mechanisms by which PENK is involved in kidney impairment and to characterize PENK kinetics during HD in this patient population.