FDA Approves Device Showing Promise in Pediatric Sepsis-Associated AKI

A novel cytopheretic device, Quelimmune, is demonstrating both safety and potential benefit for critically ill children experiencing life-threatening sepsis-associated acute kidney injury (AKI) requiring kidney replacement therapy. The device, approved by the FDA in 2024, is currently the only therapy specifically authorized for pediatric patients in the ICU facing this severe complication, offering a new avenue of treatment where previously supportive care was the standard.

A Shift in Pediatric AKI Management

Prior to the availability of Quelimmune, treatment for pediatric sepsis-associated AKI largely focused on supportive measures – fluids, antibiotics, and circulatory support – without directly addressing the underlying inflammatory processes damaging the kidneys. This approach, despite best efforts, carried a historically high mortality rate of approximately 50% in this vulnerable population, according to Stuart Goldstein, MD, director of the Center for Acute Care Nephrology at Cincinnati Children’s and a member of SeaStar Medical’s scientific advisory board.

Sepsis and sepsis-like conditions are leading causes of AKI, triggering an uncontrolled inflammatory response within the kidneys. This hyperinflammation, driven by leukocytes, can disrupt oxygen delivery and damage blood vessels and kidney tissue, severely impairing the organ’s ability to filter waste and maintain fluid balance. Quelimmune aims to modify this hyperinflammatory response, targeting the root cause of kidney dysfunction.

How Quelimmune Works: Selective Cytopheresis

The device, developed by SeaStar Medical, employs selective cytopheresis to neutralize overactive immune cells. As explained by Kevin Chung, MD, chief medical officer of SeaStar Medical, Quelimmune works alongside existing continuous renal replacement therapy (CRRT) hemofiltration systems. It specifically targets highly inflamed monocytes and neutrophils, reducing their inflammatory state without broadly suppressing the immune system. This targeted approach is crucial, as complete immunosuppression could depart patients vulnerable to secondary infections.

“One key mechanistic attribute is that only the most activated neutrophils are impacted by the device, thereby significantly reducing any risk of immunosuppression or immunodepletion,” Chung said. “By doing this, we are targeting the source of the dysregulated host response that tends to drive most of the damage that is done to the body.”

Post-Approval Study Results: Initial Findings

Recent data published in Pediatric Nephrology provide encouraging post-approval insights into the device’s performance. The study, led by Goldstein and colleagues, evaluated 21 pediatric patients (median age 9.2 years, 47% White) with sepsis-associated AKI requiring kidney replacement therapy. These 21 patients represent the first cohort in an ongoing study aiming to include 50 pediatric patients, a revised target set after the FDA granted humanitarian device exemption status in 2024, reducing the initial requirement from 300 patients.

The primary outcome assessed was the incidence of new secondary bloodstream infections within the first 28 days of treatment. Secondary outcomes included mortality rates and the duration of kidney replacement therapy. Results showed a 76% survival rate at both day 28 and day 60, and a 71% survival rate at day 90. These figures align with the data that initially supported the device’s FDA approval.

Further analysis revealed a 60% survival rate at day 90 among the five patients requiring extracorporeal membrane oxygenation (ECMO). Among the twelve patients without pre-existing finish-stage kidney disease or recent kidney transplants, a significant majority (75% at day 28 and 83% at day 90) were able to discontinue dialysis.

Importantly, the study reported no device-related adverse events or evidence of immunosuppressive effects. Three positive blood cultures were identified during treatment (at days 6, 7, and 22), but researchers determined these infections were unrelated to the device itself.

Contextualizing the Findings: Limitations and Next Steps

Even as these initial results are promising, it’s crucial to acknowledge the study’s limitations. The relatively compact sample size (21 patients) necessitates further investigation with a larger cohort to confirm these findings and assess long-term outcomes. The study population was as well not fully representative of the broader pediatric population, with a majority identifying as White. Further research is needed to determine if these results generalize to diverse racial and ethnic groups.

SeaStar Medical is continuing to collect data from the remaining patients enrolled in the study. Goldstein emphasized the significance of this progress, stating, “I have treated these critically ill children with AKI and sepsis for over 25 years. Leading the studies to achieve FDA approval and observing the continued improvement in patient outcomes after FDA approval has been one of the most rewarding accomplishments in my career.”

Beyond pediatric AKI, SeaStar Medical is exploring the potential applications of this technology in other kidney disease states, including cardiorenal syndrome, hepatorenal syndrome, and end-stage kidney disease (ESKD). An ongoing clinical trial is also evaluating the device’s efficacy in adult patients with AKI, utilizing a larger version of the device adapted for adult physiology. This trial builds on previous research linking obesity to an increased risk of sepsis-associated AKI in adults.

For more information, clinicians can contact Kevin Chung at [email protected] or Stuart Goldstein at [email protected].

The ongoing evaluation of Quelimmune and its potential expansion to other kidney disease indications represent a significant step forward in the field of nephrology, offering hope for improved outcomes for patients facing these challenging conditions. Continued research and careful monitoring will be essential to fully understand the device’s benefits and risks and to optimize its use in clinical practice.