ObjectiveTo explore the key genes of ferroptosis involved in renal tubulointerstitium of diabetic kidney disease （DKD） and its clinical relevance by bioinformatics analysis.MethodsDKD and non-DKD datasets of renal tubulointerstitial tissue were obtained to identify differentially expressed genes （DEGs）， and DKD-specific ferroptosis-related genes. Functional enrichment and protein-protein interaction network （PPI） analyses were conducted. After screening key genes， clinical correlation analysis and quantitative real-time PCR （qPCR） were performed for validation. The relationship between key genes and immune microenvironment was explored.ResultsA total of 37 ferroptosis-associated DEGs in DKD were screened， and they were mainly enriched in metabolic， lipid peroxidation， and inflammatory response signaling pathways. Among the 37 ferroptosis-related genes， 5 genes （PTEN， VEGFA， HSPA5， MAPK8， CD44， ATM） were identified as DKD-specific ferroptosis-associated genes. qPCR showed that the mRNA level of PTEN was significantly up-regulated and that of VEGFA was significantly down-regulated in high glucose-treated human kidney proximal tubular epithelial （HK-2） cells. Nephroseq data showed that the mRNA expression level of VEGFA was positively correlated with glomerular filtration rate （GFR）， and the Person correlation coefficient （r value） was 0.67 （P