Urinary podocalyxin identifies a pre-albuminuric kidney injury window and stratifies 12-year diabetic kidney disease risk in youth with type 1 diabetes mellitus

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Abstract
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.
Funding Information
  • Manisa Celal Bayar Üniversitesi

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