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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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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
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author Johnston, Kimberly A.
Pino, Christopher J.
Chan, Goldia
Ketteler, Skylar K.
Goldstein, Stuart L.
Humes, H. David
author_facet Johnston, Kimberly A.
Pino, Christopher J.
Chan, Goldia
Ketteler, Skylar K.
Goldstein, Stuart L.
Humes, H. David
author_sort Johnston, Kimberly A.
collection PubMed
description 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.
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spelling pubmed-96263912023-02-02 Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs Johnston, Kimberly A. Pino, Christopher J. Chan, Goldia Ketteler, Skylar K. Goldstein, Stuart L. Humes, H. David Pediatr Res Article 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. 2023-01 2022-05-02 /pmc/articles/PMC9626391/ /pubmed/35501373 http://dx.doi.org/10.1038/s41390-022-02061-4 Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Johnston, Kimberly A.
Pino, Christopher J.
Chan, Goldia
Ketteler, Skylar K.
Goldstein, Stuart L.
Humes, H. David
Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs
title Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs
title_full Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs
title_fullStr Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs
title_full_unstemmed Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs
title_short Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs
title_sort immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs
topic Article
url 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
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