The Clinical Significance of Serum Sirtuin 2 in Diabetic Nephropathy: Evidence for a Potential Biomarker of Renal Injury

<b>Background/Objectives:</b> Type 2 diabetes mellitus (T2DM) is a major metabolic disorder associated with progressive microvascular complications such as nephropathy, retinopathy, and neuropathy. Early detection of diabetic nephropathy (DN) remains challenging, as conventional markers such as urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are influenced by non-renal factors and lack sensitivity for subclinical injury. Sirtuin 2 (SIRT2), a cytoplasmic NAD⁺-dependent deacetylase involved in oxidative stress and inflammatory regulation, has recently been implicated in renal pathophysiology. This study aimed to assess the relationship between serum SIRT2 levels and the presence of diabetic nephropathy and to evaluate its potential utility as a complementary biomarker reflecting early renal injury. <b>Methods:</b> In this single-center, cross-sectional study, 180 participants aged 18-80 years were enrolled: 60 healthy controls, 60 T2DM patients without nephropathy (T2DM - DN), and 60 T2DM patients with nephropathy (T2DM + DN). Serum SIRT2 concentrations were quantified using a validated ELISA. Group comparisons, multinomial logistic regression, and receiver operating characteristic (ROC) curve analyses were performed to assess associations between SIRT2 and renal indices (UACR and eGFR). Statistical significance was set at <i>p</i> < 0.05. <b>Results:</b> Serum SIRT2 concentrations showed a progressive elevation across study groups (<i>p</i> < 0.001), with median levels of 6.13 ng/mL in healthy controls, 8.53 ng/mL in T2DM - DN, and 33.19 ng/mL in T2DM + DN. ROC analysis revealed good diagnostic performance for differentiating DN from healthy controls (AUC = 0.813, sensitivity 75%, and specificity 78.3%). Multivariable regression analysis identified SIRT2 as an independent correlate of DN after adjusting for metabolic and renal covariates (adjusted OR = 1.22, 95% CI 1.11-1.35, <i>p</i> < 0.001). <b>Conclusions:</b> Serum SIRT2 levels were observed to increase in parallel with the presence and severity of diabetic nephropathy and remained independently associated with the condition after adjustment for conventional risk factors. These findings suggest that SIRT2 may serve as a feasible complementary biomarker reflecting renal injury processes not captured by traditional measures. Further longitudinal studies are warranted to clarify its prognostic significance and potential for clinical integration.