Background: Sepsis and sepsis-associated acute kidney injury (AKI) are associated with increased patient morbidity and mortality. The immediate host response aimed at combating infection can become dysregulated, leading to uncontrolled inflammation and multiorgan failure, including AKI. Therapies targeting one protein component of the sepsis pathway have largely failed to improve patient outcomes, and currently only organ support therapies are used clinically to provide time for innate organ recovery to occur. Summary: The Selective Cytopheretic Device (SCD) is a continuous cell-processing immunomodulatory device that attracts activated neutrophils and monocytes to its biomimetic membrane surface. The activated leukocytes are transformed to a less pro-inflammatory phenotype and released back into the circulation when exposed to the low ionized calcium concentration established in the SCD by standard regional citrate anticoagulation protocols used in continuous renal replacement therapy. Key Messages: In this review, we detail the history of the SCD and our experience with it, from discovery to preclinical testing to translational research application at the bedside. We discuss the SCD mechanism of action, its immunomodulatory effect, and the human studies involving critically ill adult pediatric patients with AKI who require continuous renal replacement therapy as part of the standard of care. We conclude discussing ongoing and future application of the SCD in both acute and chronic inflammatory states that would benefit from immunomodulation.

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