Abstract
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 (8–15 kg) 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 6 h.
Results
SCD was readily integrated into the CARPEDIEM™ system and treatment delivered for 6 h 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 ss-SOFA scores at 6 h 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 h 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.
Impact
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SCD therapy with regional citrate anticoagulation has the potential to be administered safely to patients weighing <20 kg using the Carpediem renal replacement therapy platform.
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Use of a renal replacement therapy platform designed specifically for neonates/infants overcomes safety concerns for delivery of SCD treatment in this population.
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SCD therapy using the Carpediem renal replacement therapy platform retained the suggestive efficacy seen in larger children and adults to reduce organ injury and dysfunction from sepsis.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was generously funded through the Frankel Innovation Initiative at the University of Michigan and private donation by Stuart and Maxine Frankel and the National Institutes of Health (NIH) Small Business for Innovative Research (SBIR) program through the National Center for Advancing Translational Sciences (NCATS) award R44TR001324-02A1.
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Study design: K.A.J., C.J.P., S.L.G., H.D.H. Data collection and manuscript preparation: K.A.J., C.J.P., G.C., S.K.K. Approval: K.A.J., S.L.G., H.D.H.
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K.A.J., C.J.P., S.K.K., and H.D.H. are employees of Innovative BioTherapies (IBT). H.D.H. is a shareholder, an officer, and a director of IBT. K.A.J., C.J.P., and H.D.H. are shareholders of SeaStar Medical, Inc. C.J.P. and H.D.H. are inventors on patents held by SeaStar Medical. H.D.H. is a scientific advisor, a director, and a consultant to SeaStar Medical. S.L.G. receives consulting fees from SeaStar Medical. G.C. has no competing interests. SeaStar Medical was not involved in the execution of this study.
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Johnston, K.A., Pino, C.J., Chan, G. et al. Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs. Pediatr Res 93, 89–96 (2023). https://doi.org/10.1038/s41390-022-02061-4
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DOI: https://doi.org/10.1038/s41390-022-02061-4
