We developed a novel Sepsis-Related Death (SRD) rat model that replicates urosepsis progression. We performed multi-omics analysis (transcriptomics, proteomics, and metabolomics) on early septic kidney tissues, followed by comprehensive single-cell RNA sequencing of kidney tissues at different disease stages. We validated key findings using immunohistochemistry, immunofluorescence, large-scale public dataset integration, and analysis of clinical samples.