CSA-13 treatment in a murine model of Pseudomonas pneumonia-induced sepsis and its effects on renal injury, inflammation, and glycocalyx derangement.

Pneumonia-induced sepsis is a major cause of acute kidney injury (AKI), which can lead to high morbidity and mortality. Ceragenins, such as CSA-13, are synthetic mimics of antimicrobial peptides with known antimicrobial and immunomodulatory properties. This study aimed to evaluate the hypothesis that CSA-13, administered intraperitoneally following pneumonia-induced sepsis, was able to induce renal protection in mice. C57/BL6 female mice were randomly categorized into four groups (n = 6/group): (1) healthy control; (2) pneumonia control; (3) pneumonia followed by a low dose of CSA-13; and (4) pneumonia followed by a high dose of CSA-13. We tested CSA-13 for its effects on renal tissue IL-6 (inflammation marker) and plasma levels of cystatin C (renal injury marker). Plasma levels of hyaluronan were measured to evaluate glycocalyx degradation. Cellular integrity was assessed by histological evaluation. We found that (1) both CSA-13 doses successfully restored cystatin C; (2) high and low doses of CSA-13 decreased IL-6 levels to normal levels; (3) plasma hyaluronan remained elevated in treated and untreated mice; and (4) cellular integrity was largely maintained by the administration of either high or low doses of CSA-13. Intraperitoneal administration of CSA-13 decreases IL-6 levels in the kidneys and protects kidney function and cellular integrity in a model of pneumonia-induced sepsis. Plasma hyaluronan levels of infected mice were not substantially altered by the administration of ceragenin. CSA-13 may be helpful as a treatment protocol for pneumonia that inhibits acute kidney injury.