The role of phospholipid transfer protein in sepsis-associated acute kidney injury.

Summary

In a prospective ICU cohort (n=93) and a CLP mouse model, plasma PLTP activity within 24 hours independently predicted SA-AKI and MAKE30 (AUC 0.87 for both), with higher activity associated with fewer adverse kidney events. PLTP+/− mice had worse renal function and inflammation after CLP, while recombinant human PLTP improved 10-day survival, renal function, and mitochondrial integrity.

Key Findings

• Plasma PLTP activity within 24 h predicted SA-AKI (adjusted OR 0.92 per unit; AUC 0.87).
• PLTP activity predicted MAKE30 with AUC 0.87; high-activity group had fewer adverse kidney events.
• PLTP± mice exhibited worse renal function and higher inflammatory mediators post-CLP versus wild-type.
• Recombinant human PLTP improved 10-day survival, renal function, and reduced mitochondrial injury in CLP mice.

Clinical Implications

Early measurement of PLTP activity may aid risk stratification for SA-AKI and MAKE30; recombinant PLTP or agents that enhance PLTP function warrant evaluation as potential therapies.

Limitations

• Single-center cohort with modest sample size (n=93) may limit generalizability.
• Causality in humans remains unproven; animal model findings may not fully translate.

Future Directions

External validation of PLTP as a biomarker, dose-finding and safety studies of recombinant PLTP, and trials testing PLTP-guided therapy in SA-AKI.