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

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.

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 m²) 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.

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 m²). IL-18 was increased in NADKD and correlated positively with Rac-1 (ρ = 0.19, p = 0.005) and nephrin (ρ = 0.19, p = 0.006). These associations remained robust after adjustment for PSM and IPTW. EGF demonstrated strong diagnostic performance in predicting reduced eGFR (AUC = 0.818, p < 0.001), and VCAM-1 moderately identified albuminuria (AUC = 0.722, p < 0.001).

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.