Early Sepsis Metabolic Changes in Kidney and Liver Precede Clinical Evidence of Organ Dysfunction.

Summary

In two human sepsis cohorts and a murine polymicrobial model, blood acetylcarnitine and L-carnitine signatures indicated impaired mitochondrial β-oxidation and correlated with renal and hepatic dysfunction. These metabolite signals were organ-specific and preceded clinical indices and histologic apoptosis, positioning metabolomics for early detection of impending organ failure.

Key Findings

• In sepsis patients, blood metabolite patterns consistent with impaired mitochondrial β-oxidation correlate with renal and hepatic dysfunction.
• In mice, organ metabolism changes correlate with the blood acetylcarnitine:L-carnitine ratio and differ between liver and kidney.
• Metabolic alterations precede both clinical indices of organ function and histologic evidence of apoptosis.

Clinical Implications

Dynamic monitoring of acetylcarnitine/L-carnitine and related mitochondrial metabolites may support earlier identification of kidney and liver injury in sepsis and guide targeted metabolic therapies.

Limitations

• Causality cannot be established from correlative metabolite associations.
• External validation cohorts and clinical implementation thresholds were not defined in the abstract.

Future Directions

Validate metabolite thresholds prospectively, assess predictive performance versus standard biomarkers, and test whether metabolically targeted interventions alter organ failure trajectories.