Urinary succinate is associated with kidney injury in type 2 diabetes mellitus: a cross-sectional analysis

Objective Diabetic kidney disease (DKD) is a common microvascular complication in patients with type 2 diabetes mellitus (T2DM), yet reliable biomarkers for disease assessment and effective risk stratification remain limited. Succinate is a signaling molecule implicated in kidney diseases. This study aimed to investigate the association between urinary succinate and kidney injury in patients with T2DM. Methods Cross-sectional study of 240 participants: healthy controls (n = 25), patients with non-DKD (n =40), and 175 patients with T2DM (85 without DKD and 90 with DKD). Urinary succinate levels were measured using a colorimetric assay kit. Results Urinary succinate levels were significantly elevated in patients with T2DM but not in patients with non-DKD, with the highest levels observed in patients with DKD. Urinary succinate correlated negatively with estimated glomerular filtration rate (eGFR) and positively with serum creatinine, urinary albumin-to-creatinine ratio (UACR), urinary N-acetyl-β-D-glucosaminidase (NAG), and urinary neutrophil gelatinase-associated lipocalin (NGAL) in patients with DKD, but only correlated with urinary NAG in patients with T2DM without DKD. In multivariable liner regression analysis, urinary succinate was found to be independently associated with eGFR in patients with DKD after adjustment for age, male sex, smoking history, hypertension, HbA1c > 7.0%, uric acid, UACR, and the use of renin-angiotensin system inhibitors (RASi) and sodium-glucose co-transporter 2 inhibitors (SGLT2i). Receiver operating characteristic (ROC) analysis for detecting eGFR < 60 mL/min/1.73m 2 in DKD yielded an AUC of 0.70, with a sensitivity of 57.14% and a specificity of 75.00%. Conclusion Urinary succinate levels are elevated in patients with T2DM, particularly in DKD, but not increased in patients with non-DKD. Urinary succinate is independently associated with eGFR, and shows moderate diagnostic performance for renal insufficiency in DKD. These findings suggest that urinary succinate may serve as a potential non-invasive biomarker for diabetes-related kidney injury. Prospective studies are needed to evaluate its predictive value for early detection and disease progression of DKD.