To investigate epigenomic indices of diabetic kidney disease (DKD) susceptibility among high-risk populations with type 2 diabetes mellitus.KDIGO (Kidney Disease: Improving Global Outcomes) clinical guidelines were used to classify people living with or without DKD. Differential gene methylation of DKD was then assessed in a discovery Aboriginal Diabetes Study cohort (PROPHECY, 89 people) and an external independent study from Thailand (THEPTARIN, 128 people). Corresponding mRNA levels were also measured and linked to levels of albuminuria and eGFR.Increased DKD risk was associated with reduced methylation and elevated gene expression in the PROPHECY discovery cohort of Aboriginal Australians and these findings were externally validated in the THEPTARIN diabetes registry of Thai people living with type 2 diabetes mellitus.Novel epigenomic scores can improve diagnostic performance over clinical modelling using albuminuria and GFR alone and can distinguish DKD susceptibility.