Journal of Diabetes and Metabolic Disorders, cilt.25, sa.1, 2026 (ESCI, Scopus)
Purpose: Diabetic nephropathy (DN) remains a leading cause of chronic kidney disease and end-stage renal disease, yet early detection is challenging when diagnosis relies mainly on albuminuria and estimated glomerular filtration rate (eGFR). Podocyte injury and profibrotic signaling via the transforming growth factor-beta (TGF-β)/Smad pathway can precede overt proteinuria. In this study, we aimed that whether urinary podocyte-associated proteins and TGF-β/Smad pathway components can improve early, non-invasive identification of DN. Methods: In this cross-sectional study, adults with type 2 diabetes mellitus (T2DM) and healthy controls were recruited and categorized by urinary albumin-to-creatinine ratio (UACR) into normoalbuminuria (< 30 mg/g), microalbuminuria (30–300 mg/g), and macroalbuminuria (> 300 mg/g) groups. Urinary nephrin, podocin, podocalyxin, podoplanin, TGF-β1, Smad2, and Smad7 were measured by sandwich ELISA and normalized to urinary creatinine. Diagnostic performance for DN was assessed by receiver operating characteristic (ROC) analysis and compared with UACR. Results: Urinary nephrin, podocin, podocalyxin, TGF-β1, Smad2, and Smad7 were significantly increased in microalbuminuric and macroalbuminuric T2DM groups versus controls, and were positively correlated with diabetes duration, HbA1c, and UACR while negatively correlated with eGFR. ROC analysis demonstrated higher diagnostic accuracy for nephrin (AUC 0.848), podocin (AUC 0.854), Smad2 (AUC 0.865), and the Smad2/Smad7 ratio (AUC 0.877) than for UACR (AUC 0.805). Podoplanin did not show significant diagnostic performance. Conclusion: Urinary nephrin, podocin, and Smad2 and particularly the Smad2/Smad7 ratio show strong diagnostic characteristics for DN and may complement UACR-based screening. Prospective validation in normoalbuminuric T2DM is warranted to determine their value for predicting incident DN.