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

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 (8–15kg) 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.