Integrated causal inference, kidney transcriptomics, and experimental validation identify ChREBP (MLXIPL) as a driver of maladaptive metabolic remodeling in diabetic kidney disease

Background: ) regulates glycolytic-lipogenic programs, yet its causal contribution to renal injury is challenging to disentangle in advanced DKD, where bulk kidney transcriptomes reflect tissue remodeling and cellular compositional shifts. Methods: -high/low stratification for GSEA/GSVA and functional/network inference. Key observations were validated in db/db mice and primary proximal tubular epithelial cells (PTECs) exposed to high glucose with matched osmotic control. Results: . Conclusions: /ChREBP as a pathogenic nutrient-sensing node linking diabetes susceptibility to renal injury and maladaptive metabolic remodeling in DKD, providing a mechanistic rationale for targeting this axis to mitigate residual renal risk.