Nilay Tuğçe Işık Bayar

Microalbuminuria indices may miss early diabetic kidney disease (DKD) and can regress. Urinary podocyte and tubular injury biomarkers may detect subclinical kidney injury before albuminuria. We evaluated urinary podocyte- and tubule-derived biomarkers in adolescents/young adults with type 1 diabetes mellitus (T1DM) and compared 12-year prognostic performance with albuminuria. A total of 130 participants with T1DM were screened; 109 were eligible and included in the baseline analysis, and 30 age-matched healthy controls were enrolled. Baseline urinary podocalyxin (u-PCX), nephrin (u-nephrin), and liver-type fatty acid-binding protein (u-LFABP) were measured by ELISA and indexed to creatinine; albuminuria was assessed by 24-h albumin excretion rate (u-AER) and spot albumin-to-creatinine ratio (u-ACR). Fifty-one participants were reassessed after 12 years; measurements were obtained at baseline and at the 12-year follow-up visit. Incident DKD (micro-/macroalbuminuria) was the primary outcome. Discrimination was assessed by ROC curves and Youden thresholds. At baseline, 90% had normoalbuminuria. Participants with normoalbuminuria had higher u-PCX/Cr, u-nephrin/Cr, and u-LFABP/Cr vs. controls (all p ≤ 0.001). Over 12 years, 7/51 developed DKD. Baseline u-PCX/Cr discriminated incident DKD (AUC 0.96; 95% CI 0.91-1.00): <78 ng/mgCr (NPV 100%) and ≥193 ng/mgCr had specificity 95.5%; DKD incidence across <78, 78-193 and ≥193 ng/mgCr strata was 0%, 20% and 75%, respectively (p-trend < 0.001). Baseline spot u-ACR also performed well (AUC 0.87; 95% CI 0.74-1.00). Baseline u-PCX/Cr and u-LFABP/Cr were elevated in those who developed micro-/macroalbuminuria at 12 years. Spot u-ACR remains a practical prognostic tool, while u-PCX/Cr provides complementary, actionable long-term risk cut-points requiring external validation.