Serum Cell-Free DNA as Predictor of Progression of Kidney Disease in Diabetes: A Single-Center Prospective Study.

INTRODUCTION: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease with significant variability in progression among individuals. Identifying reliable biomarkers to predict DKD progression remains a critical unmet need. This study aimed to evaluate the role of cell-free DNA (cfDNA) as a biomarker for predicting the progression of DKD in patients with type 2 diabetes mellitus (T2DM). METHODS: In this prospective study, T2DM patients aged 18-80 years with DKD (estimated glomerular filtration rate [eGFR] 20-60 ml/min/1.73 m² and/or urinary albumin-to-creatinine ratio (UACR) 30-300 mg/gm) were recruited and were followed every 6 months for 18 months. Progression was defined as a ≥20% decline in eGFR and/or UACR > 300 mg/gm. Baseline cfDNA was retrospectively analyzed for progression of DKD. Multiple logistic regression analysis was performed to explore the association between cfDNA and the progression of DKD by adjusting in different models. RESULTS: Out of 154 T2DM patients with DKD, 140 participants completed the study and progression was found to be in 63 (45%) of patients. Median baseline cfDNA levels were significantly higher in the progressive group than in the nonprogressive group (197.23 ng/ml vs. 138.79 ng/ml, P = 0.008). cfDNA was found to be an independent predictor of DKD progression (odds ratio 1.004; 95% confidence interval: 1.001-1.006; P = 0.005). The optimal cfDNA cut-off (247.27 ng/ml) showed 44.4% sensitivity and 85.7% specificity for predicting progression of DKD. CONCLUSION: cfDNA independently predicts DKD progression in T2DM patients. However, future large-scale, long-term studies are necessary to validate these findings for clinical application.