Reflective versus predictive value of urinary podocin, nephrin, and their ratio in diabetic kidney disease: a 12-month retrospective cohort study

Introduction: Podocyte injury plays a central role in the development of diabetic kidney disease (DKD). Urinary podocin, nephrin, and the podocin-nephrin ratio (PNR) have been proposed as early indicators of glomerular injury, but their prognostic value remains uncertain. This study aimed to evaluate whether baseline urinary podocyte biomarkers reflect current disease severity and predict DKD progression. Methods: We conducted a retrospective cohort study involving 119 adults with type 2 diabetes and DKD. Baseline urinary podocin, nephrin, and PNR were measured using ELISA. Kidney outcomes were assessed over 12 months. DKD progression was defined as ≥5 mL/min/1.73 m² decline in estimated glomerular filtration rate (eGFR) and/or ≥30% increase in urine albumin-creatinine ratio (uACR). Follow-up uACR data were available for 52 participants. ROC analyses evaluated predictive performance. Results: At baseline, median eGFR was 68.1 mL/min/1.73 m² and median uACR was 112 mg/g. Over 12 months, eGFR declined significantly, while uACR showed high variability without consistent change. Among participants with complete outcome data, 19 (36.5%) experienced eGFR decline and 17 (32.7%) showed uACR progression. Baseline podocin, nephrin, and PNR were numerically higher in progressors but showed no significant group differences (all p > 0.3). Predictive performance was poor: AUCs for eGFR decline were 0.504 (podocin), 0.512 (nephrin), and 0.523 (PNR). For albuminuria progression, AUCs were 0.563, 0.524, and 0.544, respectively. Subgroup analyses similarly showed no significant predictive value. Discussion: These results suggest that single baseline measurements of podocin, nephrin, or PNR may have limited short-term prognostic value in DKD. However, the presence of these markers, even in patients with only moderate disease, supports their role as early indicators of podocyte stress. Conclusion: While urinary podocyte-associated proteins reflect early glomerular injury, their utility as stand-alone prognostic biomarkers over a one-year period may be limited. Larger longitudinal studies assessing biomarker trajectories and integrating additional molecular markers are warranted.