Reduced peripheral CD8+ T cells are associated with sepsis-associated acute kidney injury in intra-abdominal infection: a multicenter cohort and multi-omics analysis.

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is a severe complication of sepsis characterized by high mortality and limited early immune-related biomarkers. Increasing evidence suggests that immune dysregulation contributes substantially to the pathogenesis of SA-AKI; however, the immunological characteristics underlying bacterial intra-abdominal infection (IAI)-associated SA-AKI remain incompletely understood. METHODS: In this study, we investigated alterations in lymphocyte subsets and immune mediators in patients with bacterial IAI-associated sepsis. Clinical and immunological data were collected to identify independent risk factors for SA-AKI, and an immuno-nomogram was established. Public transcriptomic datasets from the Gene Expression Omnibus (GEO) database were analyzed to evaluate immune cell infiltration and immunosuppressive gene expression. Experimental validation was performed using murine LPS and CLP models with flow cytometry and immunofluorescence. RESULTS: A total of 408 patients with bacterial IAI-associated sepsis were enrolled, among whom 120 patients (29.4%) developed SA-AKI. Patients with SA-AKI exhibited significantly lower peripheral CD8+ T-cell percentages compared with those without SA-AKI. Integrated immuno-inflammatory profiling identified peripheral CD8+ T cell reduction as a prominent immune feature and an independent risk factor for SA-AKI. Incorporation of CD8+ T cell percentage into the immuno-nomogram significantly improved predictive performance compared with the clinical model alone. Transcriptomic analysis and experimental validation consistently demonstrated reduced renal CD8+ T cell infiltration accompanied by enhanced immunosuppressive signaling and elevated immunosuppressive scores. Moreover, renal CD8+ T cell abundance was inversely associated with immunosuppressive signaling. CONCLUSIONS: Collectively, these findings identify CD8+ T cell reduction as a key immunological feature of SA-AKI. Integrated clinical, transcriptomic, and experimental data support a consistent association between systemic immune alterations and kidney immune-related signatures in SA-AKI. These findings support the potential utility of CD8+ T cells as an immune-associated biomarker for risk stratification in SA-AKI.