Mitochondrial DNA copy number in diabetic kidney disease: translational prospects and challenges

Context: Diabetic kidney disease (DKD) presents substantial challenges in early detection and clinical monitoring. Mitochondrial dysfunction plays a pivotal role in DKD pathogenesis, and mitochondrial DNA copy number (mtDNA-CN) reflects this dysfunction. Objective: To evaluate the translational potential of mtDNA-CN as a biomarker for DKD, focusing on its diagnostic, prognostic, and monitoring utility across biological specimens, and examine the critical challenges of its clinical translation. Materials and Methods: We systematically synthesize evidence from cellular experiments, animal models, and clinical studies that assess mtDNA-CN alterations in DKD, with a comparative analysis of specimen types and methodologies. Results: Studies demonstrated that mtDNA-CN in blood and urine are correlated with the onset and progression of DKD. Rigorous standardization must be implemented across specimen collection, pre-analytical processing, analytical testing, detection and data reporting. Conclusion: MtDNA-CN is a promising and measurable biomarker for DKD. Combined with conventional markers, it could enhance clinical utility.