INTRODUCTION: Diabetic nephropathy (DN) is the primary complication associated with diabetes mellitus and is increasingly acknowledged as the leading cause of end-stage renal disease worldwide, placing a significant economic burden on society. This study determined how blood serpin peptidase inhibitor clade E member 2 (SERPINE2) levels affect DN in individuals with type 2 diabetes mellitus (T2DM). METHODS: We recruited 292 individuals diagnosed with T2DM and 120 healthy controls for this study. We employed comprehensive and systematic data collection methodologies to gather relevant biomarkers and information on biochemical parameters. We measured serum levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), transforming growth factor-β1 (TGFβ1), connective tissue growth factor (CTGF), and SERPINE2 by the enzyme-linked immunosorbent assay in control subjects and patients with T2DM. We calculated generalized odds ratios (OR) to estimate the risk of developing DN. RESULTS: Patients with diabetes had significantly higher levels of SERPINE2 (285.64 ± 56.58 pg/mL) than healthy controls (184.84 ± 23.54 pg/mL). Additionally, the multivariate logistic regression analysis indicated that patients with diabetes with DN possessed higher levels of serum SERPINE2 (OR 1.033, 95% confidence interval [CI] 1.013-1.053
P = 0.002), along with an increased body mass index (BMI), duration of diabetes, serum creatinine (Scr), NGAL, KIM-1, TGFβ1, and CTGF. Receiver operating characteristic (ROC) curve analysis indicated that patients with T2DM and serum SERPINE2 levels exceeding 278.94 pg/mL had a significantly higher risk of developing DN. CONCLUSION: The results showed that patients with diabetes with DN have higher levels of serum SERPINE2. A more extensive population-based prospective study is needed to validate our findings.