The Impact of the Selective Cytopheretic Device on Neutrophil-to-Lymphocyte Ratios and Hematological Parameters in Acute Kidney Injury: A Pooled Analysis

Background: The selective cytopheretic device (SCD) is an immunomodulatory cell-directed extracorporeal therapy that reprograms activated neutrophils and monocytes towards immune homeostasis in hyperinflammatory conditions such as acute kidney injury (AKI). However, clinical mechanisms remain unclear. Methods: We examined the effect of SCD treatment from prior AKI adult clinical studies on systemic inflammation through neutrophil-to-lymphocyte ratios (NLR) and other hematological measures to gain insights into the mechanism of the SCD. Linear-mixed effects regression was used to estimate differences in NLR and other hematological measures between SCD-treated patients and controls over the first 6 days after initiating continuous kidney replacement therapy (CKRT). Results: Hematological data were analyzed from 76 adult patients with AKI requiring CKRT treated with the SCD, and 32 CKRT-only control patients. SCD reduced NLR across all individual studies through day 6 of treatment, while the control group demonstrated upward trends in NLR past day 3. When analyzed as pooled groups, both cohorts displayed similar baseline NLRs (SCD = 23.6 vs. control = 21.7; p = 0.636). SCD-treated patients demonstrated a statistically significant reduction in NLR vs. control patients at day 6 (SCD = 13.3 vs. control = 25.7 at day 6; p_trend = 0.011). This difference was maintained following sensitivity analysis upon exclusion of an ICU study due to a shorter follow-up period (SCD = 13.7 vs. control = 25.6; p_trend = 0.013). NLR reductions in the SCD group were driven by decreases in neutrophils and increases in lymphocytes. No statistically significant differences were observed between groups for monocyte-to-lymphocyte ratio levels or platelets over the same treatment duration. Conclusions: In a pooled analysis of multiple AKI adult clinical studies, SCD treatment demonstrated reductions in NLR. This analysis provides further clinical mechanistic evidence of leukocyte immunomodulation in targeting the dysregulation of effector immune cells in hyperinflammatory conditions such as AKI and sepsis.