There are no definitive therapies for critically ill children who develop acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT). AKI independently multiplies short- and long-term mortality risk and approximately doubles ICU length of stay. AKI, a major complication of injury and sepsis, lacks disease-modifying therapy; CKRT, the standard of care, is supportive only. However, a recent report indicates that the goal of disease modification in AKI may soon be available.
In a recently published paper in Kidney International Reports, “Use of the Selective Cytopheretic Device in Critically Ill Children,” Dr. Stuart L. Goldstein et al. (2021) examined the use of the selective cytopheretic device (SCD) for children with AKI complicating multiple organ failure. The SCD immunomodulates activated circulating leukocytes, seemingly altering disease course in sepsis and AKI. The SCD is added to the CKRT circuit anticoagulated with regional citrate anticoagulation (RCA). The SCD sequesters activated leukocytes that are then deactivated in the low ionized calcium (iCa2+) environment promoted by conventional RCA.
To understand how the SCD could improve survival and kidney recovery in pediatric AKI, the authors point out that AKI drives inflammatory injury in remote organs. In injury or infection, regulated inflammation is a critical host defense essential to survival. AKI, however, commonly drives systemic inflammation to destructive levels; this, in turn, drives excessive neutrophil activation, which is a principal cause of microvascular injury and remote vital organ damage. This damage leads to organ failure, multi-organ dysfunction (MOD), death and disability. Controlling neutrophil activation should break this lethal cycle.
The SCD could provide a new therapeutic method to systemic inflammatory response syndrome (SIRS) and AKI by immunomodulation of activated circulating neutrophils. The SCD provides neutrophil modulation when the circuit ionized calcium is maintained less than 0.40 mmol/l using RCA. Four children’s hospitals enrolled sixteen children with multi-organ dysfunction and AKI requiring CKRT. In a conventional CKRT circuit, the SCD was added downstream of the hemofilter (between the CKRT’s hemofilter and the patient). RCA was used to maintain the circuit iCa2+ level <0.40 mmol/l; SCD treatment were delivered for a median of six days. Fifteen patients survived SCD treatment with twelve surviving to ICU discharge. All survivors were dialysis independent at 60 days. There were no SCD related adverse events. Target iCa <0.40 mmol/L was maintained for 90.2% of SCD treatment time. This observational safety study was sponsored by the US Food and Drug Administration (FDA) to evaluate the safety and feasibility of SCD in critically ill children.
The study showed that SCD therapy is feasible and can be safely delivered to pediatric AKI/MOD patients. This was a safety study not controlled or powered for efficacy. Nonetheless, the lack of SCD related adverse events, the 75% survival rate and the 100% sixty-day renal recovery rate in survivors indicate the SCD is feasible, safe, and potentially very beneficial in children with AKI and MOD.
As a pediatric critical care physician in both the academic and private sectors, I have treated and investigated AKI/MOD for 35 years. The goal has been to improve patient outcomes by moving beyond organ support in AKI, to disease modification. SCD immunomodulation puts this goal within reach. Another multi-center SCD study is now enrolling adult patients with COVID-19 infection complicated by AKI and acute respiratory distress syndrome (ARDS). Safety and efficacy will be evaluated along with SCD’s effect on COVID-19 inflammatory pathology. Subject enrollment should conclude in the coming weeks.