Kidney-targeted exosomes improve injury indices in porcine sepsis-associated AKI

Researchers investigated kidney-targeted exosomes in pigs with lipopolysaccharide-induced sepsis-associated acute kidney injury (AKI), a condition associated with impaired mitochondrial fatty acid handling. Exosomes derived from fibroblastic reticular cells or CD5L-overexpressing cells were functionalized with the kidney-targeting LTH peptide. The study evaluated therapeutic efficacy and safety and used integrated multiomic and cellular analyses to investigate associated molecular pathways.

Both exosome preparations improved systemic hemodynamics, renal microvascular perfusion, and kidney injury indices, with comparable improvements reported for kidney injury indices. Treatment reduced renal lipid-droplet and acylcarnitine accumulation. CD5L interacted with fatty acid synthase, and treatment was associated with changes in short-chain fatty acids and AMPK-ACC-CPT1A signaling. These changes accompanied improved mitochondrial bioenergetic indices, preserved mitochondrial morphology, and reduced markers of tubular cell pyroptosis.

The findings support further investigation of renal lipid metabolism as a therapeutic target in sepsis-associated AKI, but do not establish efficacy in patients. The supplied report does not provide sample size, numerical effect estimates, treatment timing, or detailed safety results. Translation from a lipopolysaccharide-induced animal model to human sepsis remains uncertain.