Urinary Biomarker Profiles Define Divergent Pathways in Albuminuric and Non-Albuminuric Diabetic Kidney Disease.

[INTRODUCTION] Diabetic kidney disease (DKD) presents with distinct phenotypes, including albuminuric (ADKD) and non-albuminuric DKD (NADKD), which are not fully distinguished by conventional clinical markers. This study aimed to evaluate urinary biomarkers indicative of nephron injury - nephrin, epidermal growth factor (EGF), vascular cell adhesion molecule-1 (VCAM-1), interleukin-18 (IL-18), and Rac-1 (Ras-related C3 botulinum toxin substrate) across various DKD phenotypes.

[METHODS] In this cross-sectional study, 211 patients with type 2 diabetes mellitus were categorized into four groups based on estimated glomerular filtration rate (eGFR ≥ or <60 mL/min/1.73 m) and albuminuria (UACR ≥ or <30 mg/g). Urinary biomarker levels were quantified using ELISA. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to minimize confounding.

[RESULTS] EGF levels were significantly higher in the NADKD compared to the ADKD group. VCAM-1 was elevated in individuals with albuminuria and those with mildly reduced eGFR (<90 mL/min/1.73 m). IL-18 was increased in NADKD and correlated positively with Rac-1 (ρ = 0.19, = 0.005) and nephrin (ρ = 0.19, = 0.006). These associations remained robust after adjustment for PSM and IPTW. EGF demonstrated strong diagnostic performance in predicting reduced eGFR (AUC = 0.818, < 0.001), and VCAM-1 moderately identified albuminuria (AUC = 0.722, < 0.001).

[CONCLUSIONS] Higher EGF levels in the NADKD group suggest preserved tubular integrity, whereas elevated VCAM-1 in patients with albuminuria and mildly reduced eGFR indicate early vascular involvement. Positive correlations between IL-18, Rac-1, and nephrin imply a shared inflammatory and glomerular injury pathway. These results support the use of urinary biomarkers for early detection and phenotypic classification of DKD.