Abstract
OBJECTIVE: Diabetic kidney disease (DKD) is increasingly recognized as a leading cause of chronic kidney disease (CKD) worldwide. Although N6-methyladenosine (m6A) mRNA modification is abundant in eukaryotes, its specific contribution to DKD pathogenesis is not well understood. This study aims to investigate the role of N6-methyladenosine (m6A) RNA modification patterns in DKD and their relationship with immune regulation. METHODS: Three GEO datasets were analyzed to explore m6A modification patterns. Random forest modeling and consensus clustering were used for subtype identification. Immune cell infiltration was evaluated using ssGSEA. Key candidate genes were refined through LASSO regression and experimental verification in diabetic mouse models via qPCR. RESULTS: Eight differentially expressed m6A regulators were identified in DKD. Two distinct m6A modification patterns were established, with cluster B showing enhanced immune cell infiltration. WTAP positively correlated with immune cell populations, while YTHDC2 showed negative correlations. CTSS and CD53 were identified as potential biomarkers and validated in diabetic mouse models, showing negative correlations with glomerular filtration rate. CONCLUSIONS: This study reveals two m6A methylation patterns in DKD, with one associated with increased immune infiltration. We identified CTSS and CD53 as hub genes and validated them in diabetic mouse kidney tissues, suggesting their potential as clinical biomarkers for DKD. CLINICAL TRIAL NUMBER: Not applicable.