Serum Proenkephalin A as a Marker of Renal Dysfunction and Glycemic Status in Diabetic Nephropathy

Introduction: Traditional biomarkers like creatinine and estimated glomerular filtration rate (eGFR) often fail to detect early diabetic nephropathy. Proenkephalin A (PENK-A), a stable, kidney-specific peptide, has emerged as a potential alternative biomarker. This study aimed to evaluate serum PENK-A levels in diabetic nephropathy and their association with renal and clinical parameters. Methods: In this prospective cross-sectional study, PENK-A levels were compared between patients with type 2 diabetes and healthy controls. Biochemical variables were assessed, and receiver operating characteristic (ROC) analysis was used to determine diagnostic performance. Binary logistic regression was conducted to identify independent predictors of elevated PENK-A levels. Results: A total of 120 participants (90 patients, 30 controls) were included. PENK-A levels were significantly higher in patients and correlated with lower eGFR, higher urea, and microalbuminuria. At a cut-off value of 2.25 pmol/L, PENK-A demonstrated moderate diagnostic accuracy (AUC = 0.702, p = 0.001), with high specificity (83.3%) and positive predictive value (90.6%). Logistic regression revealed an independent inverse association between PENK-A and HbA1c, while eGFR showed a borderline relationship. Conclusion: Serum PENK-A may serve as a supportive biomarker for renal dysfunction in diabetic nephropathy. Its relationship with HbA1c suggests possible links to metabolic stress. PENK-A could complement traditional markers, particularly in early detection or high-risk patients. Further longitudinal studies are warranted to confirm its prognostic value.