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Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs

BACKGROUND: Application of the immunomodulatory Selective Cytopheretic Device (SCD) to enhance renal replacement therapy and improve outcomes of acute kidney injury in pediatric patients is impeded by safety concerns. Therapy using a pediatric hemodialysis system could overcome these limitations. ME...

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Detalles Bibliográficos
Autores principales: Johnston, Kimberly A., Pino, Christopher J., Chan, Goldia, Ketteler, Skylar K., Goldstein, Stuart L., Humes, H. David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9626391/
https://www.ncbi.nlm.nih.gov/pubmed/35501373
http://dx.doi.org/10.1038/s41390-022-02061-4
Descripción
Sumario:BACKGROUND: Application of the immunomodulatory Selective Cytopheretic Device (SCD) to enhance renal replacement therapy and improve outcomes of acute kidney injury in pediatric patients is impeded by safety concerns. Therapy using a pediatric hemodialysis system could overcome these limitations. METHODS: Yucatan minipigs (8–15kg) with induced septic shock underwent continuous hemodiafiltration with the CARPEDIEM pediatric hemodialysis system using regional citrate anticoagulation (RCA) with or without SCD (n=5 per group). Circuit function plus hemodynamic and hematologic parameters were assessed for 6h. RESULTS: SCD was readily integrated into the CARPEDIEM(™) system and treatment delivered for 6 hours without interference with pump operation. SCD treated pigs maintained higher blood pressure (p=0.009) commensurate with lesser degree of lactic acidosis (p=0.008) compared to pigs only receiving hemodiafiltration. Renal failure occurred in untreated pigs while urine output was sustained with SCD therapy. Neutrophil activation levels and ssSOFA scores at 6 hour trended lower in the SCD treated cohort. CONCLUSIONS: SCD therapy under RCA was safely administered using the CARPEDIEM(™) pediatric hemodialysis system for up to 6 hours and no circuit compatibility issues were identified. Sepsis progression and organ dysfunction was diminished with SCD treatment in this model supportive of therapeutic benefit of this immunomodulatory therapy.