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


KAYGUSUZ Y., Özbek D. A., ERDUT A., Abanoz R., Korkut M. G., ÖZDEDE M., ...More

Kidney Diseases, pp.330-345, 2026 (SCI-Expanded, Scopus) identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2026
  • Doi Number: 10.1159/000550855
  • Journal Name: Kidney Diseases
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Directory of Open Access Journals
  • Page Numbers: pp.330-345
  • Keywords: Epidermal growth factor-1, Interleukin-18, Non-albuminuric diabetic kidney disease, Ras-related C3 botulinum toxin substrate-1, Vascular cell adhesion molecule-1
  • Hacettepe University Affiliated: Yes

Abstract

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 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. 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 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). 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.