The translational potential of m6A RNA methylation in DKD: emerging biomarkers for early detection and targeted therapies.

Diabetic Kidney Disease (DKD) is a primary cause of end-stage renal disease, characterized by podocyte dysfunction. While current clinical biomarkers including albuminuria and estimated glomerular filtration rate are foundational for diagnosis, they often function as lagging indicators and fail to detect early renal injury. Recently, N6-methyladenosine (m6A) RNA methylation has emerged as a key epitranscriptomic link between hyperglycemia and podocyte injury, offering a novel frontier for diagnostic biomarker discovery. This review shifts the traditional focus from basic molecular mechanisms to the preclinical translational potential of m6A regulators and their downstream targets as early detection tools. Current experimental evidence in cell and animal models indicates that the abnormal upregulation of METTL3, METTL14, and FTO may reshape podocyte fate through complex regulatory pathways. These alterations appear to enhance the stability of harmful transcripts while degrading protective ones. Furthermore, specific regulators and their associated hub genes, such as CTSS and CD53, show emerging promise as candidate non-invasive biomarkers that correlate with immune infiltration and early renal function decline in preclinical settings, though robust clinical validation remains necessary.