Serum phoenixin-14 levels in chronic kidney disease and hemodialysis patients: a cross-sectional study

Background Phoenixin-14 (PNX-14) is a bioactive peptide associated with mitochondrial function, oxidative stress responses, and cellular protection. Although experimental data suggest a possible role in renal injury, its serum levels in chronic kidney disease (CKD) have not been previously studied. Given the limitations of conventional renal biomarkers, PNX-14 may offer additional information regarding renal dysfunction in CKD. Methods This single-center, prospective, observational, cross-sectional study included 140 adult patients with Stage 3 CKD ( n = 30), Stage 4 CKD ( n = 30), Stage 5 CKD ( n = 30), and end-stage kidney disease receiving maintenance hemodialysis (HD) ( n = 50). Serum PNX-14 was measured using a commercial ELISA kit, before and after dialysis in HD patients. Associations between PNX-14 and clinical and laboratory parameters were assessed using Spearman correlation. Receiver operating characteristic (ROC) curve analysis evaluated the discriminative performance of PNX-14 across CKD stages. Results Serum PNX-14 levels increased progressively with advancing CKD stage, from a median of 17.88 (IQR 15.16–20.20) pg/mL in Stage 3–43.14 (IQR 23.78–95.71) pg/mL in the HD group ( p < 0.001). Post hoc analysis showed that PNX-14 levels were significantly lower in Stage 3 than in Stage 5 and HD, in Stage 4 than in HD, and in Stage 5 than in HD. PNX-14 showed significant positive correlations with creatinine and parathyroid hormone (PTH) and a significant negative correlation with eGFR (all p < 0.001). In the pre-dialysis subgroup, PNX-14 remained significantly correlated with creatinine, eGFR, urea, and PTH. In HD patients, no significant difference was observed between pre-dialysis and post-dialysis PNX-14 levels ( p = 0.152), and no significant correlation was found between PNX-14 and Kt/V. ROC analysis demonstrated good discriminative performance for distinguishing Stage 3 from advanced disease (Stage 5 + HD), with an AUC of 0.839 (95% CI: 0.755–0.913). The optimal cut-off was 19.59 pg/mL, with 87.5% sensitivity and 73.3% specificity. Conclusions Serum PNX-14 levels increase with worsening CKD stage and are strongly associated with renal function parameters. Its limited change after HD and its discriminative performance suggest that PNX-14 may provide clinically relevant information regarding disease severity in CKD. Further prospective and longitudinal studies are needed to clarify its potential clinical utility.