Urinary Succinate Emerges as Potential Non-Invasive Biomarker for Diabetic Kidney Disease

Despite the prevalence of T2DM, the reliable identification of robust and accessible biomarkers for early disease assessment and effective risk stratification remains a critical challenge within nephrology. This cross-sectional study investigated the association between urinary succinate levels and the progression of kidney injury in a cohort of individuals with T2DM.

Urinary succinate concentrations were quantified utilizing a specific colorimetric assay kit. This rigorous design allowed researchers to compare succinate profiles across the spectrum of diabetic kidney health, from normoglycemic controls through to established DKD.

The results demonstrated a clear pattern of succinate elevation directly linked to the presence of T2DM. Furthermore, the highest concentrations of urinary succinate were consistently observed within the group of patients diagnosed with DKD, suggesting a correlation between higher succinate excretion and more advanced renal impairment.

A detailed correlational analysis further illuminated the relationship between urinary succinate and various established markers of kidney damage. Conversely, it displayed positive correlations with several key indicators of renal injury, including serum creatinine, the urinary albumin-to-creatinine ratio (UACR), urinary N-acetyl-β-D-glucosaminidase (NAG), and urinary neutrophil gelatinase-associated lipocalin (NGAL). Interestingly, in the subset of T2DM patients who did not yet have DKD, the correlation was more limited, showing association only with urinary NAG.

To establish the independent clinical significance of these findings, a multivariable linear regression analysis was performed specifically on the DKD patient cohort. This sophisticated statistical approach allowed researchers to isolate the effect of urinary succinate from numerous confounding variables. The analysis adjusted for several critical factors known to influence renal function and metabolic status, including age, male sex, smoking history, hypertension, HbA1c levels greater than 7.0%, uric acid levels, UACR, and the concurrent use of common therapeutic agents such as renin-angiotensin system inhibitors (RASi) and sodium-glucose co-transporter 2 inhibitors (SGLT2i). After these adjustments, urinary succinate was confirmed to be independently associated with eGFR in patients with DKD, substantiating its independent biological relevance to renal function decline.

The diagnostic potential of urinary succinate was further assessed through Receiver Operating Characteristic (ROC) analysis, specifically targeting the identification of individuals with eGFR below the threshold of 60 mL/min/1.73m2, a common definition of chronic kidney disease. For this specific application within the DKD population, the ROC analysis yielded an Area Under the Curve (AUC) of 0.70. This performance metric, alongside a sensitivity of 57.14% and a specificity of 75.00%, indicates that urinary succinate possesses moderate diagnostic capabilities for detecting renal insufficiency in the context of DKD.

The collective findings strongly suggest that urinary succinate may serve as a promising, non-invasive biomarker for the detection and monitoring of diabetes-related kidney injury. The consistent elevation across the T2DM spectrum, and its independent association with declining eGFR in DKD, positions succinate as a molecule worthy of deeper investigation in clinical settings. However, the current study design is cross-sectional, which inherently limits the ability to definitively establish causality or predict future outcomes. Therefore, the authors emphasize the necessity for future prospective studies to fully evaluate the predictive value of urinary succinate for the early detection of DKD and its subsequent progression over time.

In summary, this research provides substantial evidence that urinary succinate levels are significantly elevated in patients with T2DM, particularly those with established DKD, and that these levels correlate with reduced kidney function. The independent association with eGFR, even after accounting for complex clinical variables like hypertension and diabetes medications, underscores the unique utility of succinate as a potential diagnostic indicator for diabetic kidney disease. While the current evidence points toward its utility, further longitudinal research is essential to confirm its predictive power in the clinical management of DKD.

Subject of Research: The association between urinary succinate levels and kidney injury progression in patients with type 2 diabetes mellitus.

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

Article References: Cai, T., Jiao, Y., Chen, X., Kong, X., Chen, C., Chen, H., Zhang, Y., Hua, J., Liu, X., Cai, B., Zhu, X., & Wang, L. (2026). Urinary succinate is associated with kidney injury in type 2 diabetes mellitus: a cross-sectional analysis. Frontiers in Endocrinology, 17, Article 1908195. https://doi.org/10.3389/fendo.2026.1908195

Image Credits: AI Generated

DOI: 10.3389/fendo.2026.1908195

Keywords: Diabetic Kidney Disease, Urinary Succinate, Type 2 Diabetes Mellitus, Biomarker, Nephrology, Kidney Injury, Cross-sectional Study, eGFR, Metabolic Syndrome, Urinary, succinate, associated