Lactate and lactylation in sepsis-associated acute kidney injury: clinical evidence from the MIMIC-IV database and mechanistic insights.

Summary

In 11,431 ICU sepsis patients, higher admission lactate and lower lactate clearance independently predicted SA-AKI, CRRT use, and mortality, with a nonlinear risk inflection above ~5.7 mmol/L. In CLP mice, kidney-specific protein lactylation increased, suggesting a mechanistic link between lactate metabolism and renal vulnerability.

Key Findings

• Elevated lactate independently associated with higher SA-AKI risk, CRRT use, and 28-day mortality in 11,431 sepsis patients.
• Restricted cubic spline identified a nonlinear risk increase with an inflection around 5.7 mmol/L.
• CLP mice showed kidney-specific upregulation of protein lactylation, suggesting a mechanistic link to renal injury.

Clinical Implications

Incorporate admission lactate and lactate clearance into SA-AKI risk models and early nephroprotective strategies. Consider monitoring lactylation-related pathways as potential therapeutic targets pending further validation.

Limitations

• Observational retrospective design with residual confounding; sepsis phenotyping based on EHR
• Mechanistic lactylation evidence limited to mice; human kidney tissue validation lacking

Future Directions

Validate lactylation signatures in human kidney tissue/urine, test lactate/lactylation-modulating interventions, and integrate lactate dynamics into predictive tools for SA-AKI.