Differential Mitochondrial DNA Copy Number and Redox/Inflammatory States in Diabetic and Nondiabetic Chronic Kidney Disease: A Study in a South Indian Cohort

BACKGROUND: Chronic kidney disease (CKD) is a global health challenge, with diabetic kidney disease being a major cause in India. Mitochondrial dysfunction is central to kidney injury, and mitochondrial DNA copy number (mtDNA-CN) reflects mitochondrial health. This study compared mtDNA-CN in urine cell pellets from diabetic CKD (DCKD), non-DCKD (NDCKD), and healthy controls (HC) in a South Indian cohort. MATERIALS AND METHODS: This prospective, cross-sectional study included 75 participants (25 DCKD, 25 NDCKD, 25 HC). Urine cell pellet mtDNA-CN was measured by qPCR. Statistical analysis used ANOVA/Kruskal-Wallis tests ( P < 0.05 significant). RESULTS: Participants averaged 55.08 ± 13.24 years old. DM patients showed significantly higher mtDNA-CN than non-DM patients (93.96 ± 14.01 vs. 49.04 ± 22.28; P = 0.0001). While no difference existed between CKD Stage III and IV, overall mtDNA-CN varied significantly across No CKD, Stage III, and Stage IV groups ( P = 0.0001). A progressive increase in mtDNA-CN was observed from HC (31.84 ± 13.41) to NDCKD (66.24 ± 14.74) and then to DCKD (93.96 ± 14.01), with highly significant differences among these groups ( P = 0.0001). CONCLUSION: Our findings indicate a progressive increase in urine cell pellet mtDNA-CN across healthy individuals, NDCKD, and DCKD. This pattern, particularly in DCKD, may reflect a compensatory mitochondrial response to metabolic stress, suggesting mtDNA-CN as a promising noninvasive biomarker for disease monitoring.