Serum Humanin in Pediatric Septic Shock Associated Multiple Organ Dysfunction Syndrome

Abstract

Background: Multiple organ dysfunction syndrome (MODS) disproportionately contributes to pediatric sepsis morbidity. Humanin (HN) is a small peptide encoded by mitochondrial DNA and thought to exert cytoprotective effects in endothelial cells and platelets. We sought to test the association between serum HN (sHN) concentrations and MODS in a prospectively enrolled cohort of pediatric septic shock. Methods: Human MT-RNR2 ELISA was used to determine sHN concentrations on day 1 and 3. The primary outcome was thrombocytopenia associated multi-organ failure (TAMOF). Secondary outcomes included individual organ dysfunctions on day 7. Associations across pediatric sepsis biomarker (PERSEVERE) based mortality risk strata and correlation with platelet and markers endothelial activation were tested. Results: 140 subjects were included in this cohort, of whom 39 had TAMOF. The concentration of sHN was higher on day 1 relative to day 3, and among those with TAMOF phenotype in comparison to those without. However, the association between sHN and TAMOF phenotype was not significant after adjusting for age and illness severity in multivariate models. In secondary analyses, sHN was associated with presence of day 7 sepsis-associated acute kidney injury (SA-AKI) (p=0.049). Further, sHN was higher among those with high PERSEVERE-mortality risk strata and correlated with platelet counts and several markers of endothelial activation. Conclusion: Future investigation is necessary to validate the association between sHN and SA-AKI among children with septic shock. Further, mechanistic studies that elucidate the role of humanin may lead to therapies that promote organ recovery through restoration of mitochondrial homeostasis among those critically ill.