Early Post-Approval Experience of The Selective Cytopheretic Device Surveillance Registry for Pediatric AKI Requiring Kidney Replacement Therapy

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Goldstein, Kelli Krallman, Meredith Harris, Rajit Basu, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7988526/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Feb, 2026 Read the published version in Pediatric Nephrology → Version 1 posted 4 You are reading this latest preprint version Abstract Background The selective cytopheretic device for pediatrics (SCD-PED) was granted a Humanitarian Device Exemption (HDE) in 2024 by United States Food and Drug Administration (FDA) for treatment of critically ill children weighing ≥ 10 kilograms with AKI due to sepsis or a septic condition on antibiotics and requiring CKRT. FDA required a post-approval surveillance registry to collect additional safety data among all patients treated with SCD-PED under the HDE as part of the approval. Methods The S CD-PED Pedi A tric Sur V eillance R E gistry (SAVE; NCT06517810) will enroll up to 300 patients initiated on SCD-PED therapy under the HDE-approved indication. The primary outcome is a new (secondary) blood stream infection in the first 28 days after SCD-PED initiation. Additional Day 28 and Day 90 clinical outcomes including mortality and KRT requirement will be collected. Results Registry design and preliminary outcomes from the first 21 patients are reported. Three new positive blood cultures were observed during the follow-up period after cessation of SCD-PED therapy, all of which were deemed unrelated to SCD. Sixteen (76%) and 15 (71%) of 21 patients survived through to Day 60, and 90, respectively. Three patients died while receiving SCD-PED therapy. No device-related adverse events were reported. Conclusion This initial real-world experience of SCD-PED therapy in pediatric AKI with sepsis in patients requiring CKRT suggests no device-related infections and similar improved clinical outcomes consistent with the previous trial SCD-PED experience in this critically ill population. SCD selective cytopheretic device immunomodulation acute kidney injury kidney replacement therapy sepsis Figures Figure 1 Figure 2 Background Acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT) is a serious and often life-threatening condition in pediatric patients, particularly those with concomitant sepsis or a septic-like condition. Sepsis associated AKI is characterized by a dysregulated immune response, systemic inflammation, and endothelial dysfunction, all of which contribute to the historically poor outcomes observed in this population.[ 1 ] Current therapeutic strategies for managing pediatric sepsis-associated AKI remain limited and are supportive in nature, necessitating innovative approaches to enhance patient survival.[ 2 ] In a multicenter study from the prospective pediatric CKRT (ppCRRT) registry of 116 children with multiorgan dysfunction (MOD) receiving CKRT including 47 (39%) with sepsis, ICU survival was 51.7%.[ 3 ] A recent single-center study of children receiving CKRT revealed a similar survival rate in 130 patients receiving a vasoactive medication (50.0%) or mechanical ventilation (50.7%) on CKRT.[ 4 ] A recent multicenter (32 centers, 7 countries) study from the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Diseases (WE-ROCK) of 980 patients (Birth- 25 years of age) who received CKRT for AKI or pathologic fluid accumulation reported 64.1% survival to ICU discharge.[ 5 , 6 ] A secondary analysis from the same cohort showed patients with sepsis at CKRT initiation were less likely to liberate from CKRT by 28 days (30% vs. 38%; p < 0.001), and had higher mortality rates (47% vs. 31%; p < 0.001) compared to non-septic patients.[ 7 ] The selective cytopheretic device for pediatrics (SCD-PED) represents a potential breakthrough in the management of patients with sepsis associated AKI requiring CKRT. The SCD-PED is a novel cell-directed immunomodulatory therapy that is connected in series to a commercially available CKRT circuit, and in the presence of regional citrate anticoagulation, it modulates inflammation by targeting pro-inflammatory neutrophils and monocytes to shift them to a lower inflammatory phenotype.[ 8 ] The resulting physiological consequences are abatement of the hyperinflammatory milieu, a return to immune homeostasis and restoration of organ function within the patient. Pooled analysis from two prospective multicenter studies (n = 22 children with AKI requiring CKRT and MOD weighing ≥ 10 kg) demonstrated a 77% survival rate, with no device-related serious adverse events observed.[ 9 ] Importantly, none of the survivors were dialysis-dependent at 60 days, and 87.5% had recovered normal kidney function. Based on these findings, the SCD-PED ( QUELIMMUNE™ , SeaStar Medical, Denver, CO) received Humanitarian Device Exemption (HDE) approval from United States Food and Drug Administration for use in critically ill children ≥ 10 kg with AKI accompanied by sepsis or septic conditions receiving antibiotics and requiring CKRT. As part of this approval, FDA required a post-approval surveillance registry to collect additional safety data prospectively among all patients treated with the device under the HDE. We report the study design of the S CD-PED Pedi A tric Sur V eillance R E gistry, (SAVE Registry) and preliminary results from the first 21 patients treated post-approval, including those in SAVE. Methods The SAVE Registry (ClinicalTrials.gov identifier: NCT06517810; Primary IRB: Cincinnati Children’s Hospital: 2024 − 0153; 25-April-2024) is a mandatory, prospective, post-approval surveillance registry with a primary objective to collect descriptive safety data on the clinical use of the SCD-PED under the HDE. We anticipate approximately 50 participating institutions in the United States will enroll up to 300 patients in the registry. Each patient treated with SCD-PED therapy according to its FDA-approved indication under the HDE will be enrolled in the registry. All enrolled patients will receive the standard of care ICU treatment for those undergoing CKRT. There are no specific exclusion criteria for the registry. Additionally, patients treated with the SCD-PED under Expanded Access will be included in the registry, if informed consent is obtained. Informed consent/assent for the registry is mandatory prior to therapy. The treatment period (see Fig. 1 ) begins when the patient starts SCD-PED therapy and will continue until therapy completion. Therapy completion is defined as > 72 hours without re-initiation of SCD-PED therapy. In contrast to the SCD-PED clinical studies, where the treatment duration was limited to ≤ 10 days, the treatment duration will be determined by the clinical team and can exceed 10 days. Follow-up will continue out to 90 days. At baseline, demographic data, hospitalization data and CKRT data will be collected (see Fig. 2 ). During the treatment period, CKRT parameters, SCD-PED performance, adverse events of special interest, and other parameters will be collected. The primary outcome is a new (secondary) blood stream infection (BSI) in the first 28 days after SCD-PED initiation or through hospital discharge, whichever is sooner. A matched cohort of CKRT patients with sepsis who did not receive treatment with SCD-PED from the WE-ROCK registry 3 will serve as controls. Additional outcomes (see Fig. 2 ) collected at Day 28 include patient survival status, hospitalization status, kidney replacement therapy status, cardiorespiratory support, most recent serum creatinine, adverse events, and events of interest. An additional follow up at Day 90 is being performed to match the WE-ROCK dataset for patient status, hospitalization status, kidney replacement therapy status, and most recent serum creatinine. An independent data and safety monitoring board (DSMB), composed of 2 clinicians and a biostatistician, will regularly review safety data throughout the registry in accordance with FDA guidance. The board will assess adverse events, bloodstream infections, and deaths, meeting at least quarterly and ad hoc as needed. To support objective oversight, the DSMB operates under a formal charter and has already established data review protocols. Initial post-approval outcomes analysis included patients enrolled in SAVE, as well patients treated under emergency use post-approval who could not be included into the registry. Results The SAVE Surveillance Registry was initiated in July 2024 and preliminary outcomes data are available from 20 patients across five registry sites. Of the 20 patients, two patients were treated under emergency use due to not meeting the HDE indication criteria. One patient exceeded the upper age limit of 22 years, and the other had a body weight below 10 kg. Following treatment, both individuals were subsequently included in the registry to facilitate the collection of safety and outcome data. One additional patient was treated under emergency use at a 6th site and was recently published as a case report,[ 10 ] but could not be included in SAVE due to lack of informed consent for the registry. However, since this episode occurred after HDE approval, data from this case are included for this analysis, resulting in a total of 21 patients available for early outcome analysis. Treated patients were critically ill with AKI or acute kidney worsening requiring CKRT, had sepsis, and a variety of severe underlying illnesses with significant complexities, including those with malignancies, history of kidney transplant and/or ESRD, chronic immunosuppression or immunodeficiencies, and open wounds (see Supplementary Table 1 for individual patient characteristics and hospital/ICU diagnoses). Unless otherwise noted, all metrics refer to the cohort of 21 patients. Median age at ICU admission was 9.2 years (interquartile range [IQR]: 5.3,16.8; range 1.1–23.7; n = 21), and median weight was 21.5 kg (IQR: 16.5, 45.1; range 9-105; n = 17) (Table 1 ). The cohort was 47% White, 19% Hispanic, 10% Black, 5% Asian/Pacific Islander, with 19% of other/unknown background. Median PRISM III score at ICU admission was 15 (IQR: 8, 22; range 0–31). At the time of SCD-PED initiation, median PELOD-2 score was 9 (IQR: 6, 11; range 3–15) and all patients were receiving vasoactive medications and mechanical ventilation. Nearly 20% of patients (4 / 21) had a history of ESRD and/or kidney transplant and were KRT dependent prior to treatment (Supplementary Table 2) and 33% (7 / 21) had receipt of extracorporeal membrane oxygenation (ECMO) either concomitantly (n = 5) with or immediately prior (n = 2) to treatment with SCD-PED. The median number of SCD treatment courses was 1 (IQR: 1, 1; range 1–3), and the median total duration of therapy (DoT) was 5 days (IQR: 2,10; range 1–33). The median days from CKRT to SCD-PED initiation was 2 (IQR: 0, 4; range 0, 97), with 6 patients initiated within a 24-hour period (median of 4.5 hours [IQR: 0, 15.35; range 0, 19.8]). The SCD-PED devices were switched out every 24 hours per protocol throughout the treatment course. Table 1 Patient Demographics & Baseline Details Category (N = # of patients with data reported) Results Patients Enrolled 21 Median (IQR) Age, years (N = 21) 9.2 (5.3, 16.8) Median (IQR) Weight, kg (N = 17) 21.5 (16.5, 45.1) Median (IQR) Height, cm (N = 17) 113 (99.8, 152.4) Sex (Male / Female) (N = 21) 11/10 Median (IQR) PRISM III Score at ICU admission (N = 19) 15 (8, 22) Median (IQR) PELOD-2 Score at SCD-PED initiation (N = 20) 9 (6, 11) Receipt of Vasoactive Medications (%) (N = 21) 21 (100) Intensive Mechanical Ventilation (%) (N = 21) 21 (100) Received Extracorporeal Membrane Oxygenation (N = 19) : Concurrently with SCD-PED, n (%) Prior to SCD-PED, n (%) 5 (25) 2 (10) MedHx of ESRD and/or Recent Kidney Transplant Prior to Treatment (%) 4 (20) Median (IQR) Days from ICU to CKRT (N = 21) 4 (0, 18) Median (IQR) Days from CKRT to SCD-PED Start (N = 21) 2 (0, 4) Median (IQR) SCD-PED Treatment Days (per course) (N = 21) 5 (2, 10) Median (IQR) SCD-PED Treatment Course (N = 21) 1 (1,1) CKRT, continuous kidney replacement therapy; ESRD, end-stage renal disease; ICU, intensive care unit; IQR, interquartile range; MedHx, medical history; PELOD-2, pediatric logistic organ dysfunction-2 score; PRISM III, pediatric risk of mortality score; SCD-PED, selective cytopheretic device for pediatrics Outcomes data were available for all 21 patients at the time of this analysis (Table 2 ). Three patients had positive blood cultures at 6, 7, and 22 days after the termination of SCD-PED therapy. One culture was positive (ampicillin-resistant Klebsiella ) for ~ 32 hours and was negative the following day, while the other two cultures were positive for Enterococcus and Enterobacter . All infections were deemed unrelated to SCD-PED by the treating clinician and the DSMB. Additionally, there were no device-related adverse events reported, including no reports of immunosuppressive effects (e.g., leukopenia or neutropenia). Sixteen (76%) of 21 patients survived through the Treatment Period, Day 28, and Day 60. Three patients died while receiving SCD-PED therapy. Fifteen (71%) of 21 patients survived through Day 90. Three of 5 patients concomitantly treated with SCD-PED and ECMO survived to Day 90. Among the survivors who were not KRT dependent prior to treatment, 9 out of 12 (75%) and 10 out of 12 (83%) patients were KRT independent at Day 28 and Day 90, respectively. Individual Day 28, 60, 90, and KRT patient outcomes are listed in Supplementary Table 3. Table 2 Preliminary Results Category Results Patients Enrolled 21 Device-Related Events 0 Positive Blood Cultures : During Treatment Period During Follow-up Period (28 days post-initiation) Deemed as Related to SCD-PED by DSMB and PI 0 3 0 Survival : Day 28, n (%) Day 60, n (%) Day 90, n (%) All Patients 16/21 (76) 16/21 (76) 15/21 (71) ECMO only † 3/5 (60) 3/5 (60) 3/5 (60) Hx ESRD/Tx ‡ 4/4 (100) 4/4 (100) 3/4 (75) KRT Independence Among Survivors : Day 28, n (%) Day 90, n (%) 9/12 (75) 10/12 (83) † 5 patients with concomitantly treated with SCD-PED and ECMO; ‡ 4 patients were KRT-dependent prior to SCD-PED therapy; of these, 4 patients at Day 28 and 3 at Day 90 were excluded for the KRT is outcome as they were KRT-dependent prior to SCD-PED treatment. DSMB, data safety monitoring board; ECMO, extracorporeal membrane oxygenation; ESRD, end-stage renal disease; Hx, medical history; PI, principal investigator; KRT, renal replacement therapy; SCD-PED, selective cytopheretic device for pediatrics; Tx, kidney transplant. Discussion Pediatric AKI requiring CKRT in the setting of sepsis and/or MOD continues to result in significant morbidity and mortality. Here we report the first real-world clinical experience of SCD-PED therapy in this critically ill pediatric population including patients from the FDA-mandated SAVE registry as part of the HDE. The HDE approval of SCD-PED ( QUELIMMUNE™ ) for pediatric sepsis-associated AKI requiring CKRT was based on safety and probable benefit demonstrated in a cohort of 22 patients. Because the approval of SCD-PED was predicated on a relatively small patient population, FDA mandated the implementation of a post-market registry to monitor the safety profile of the device, especially as it relates to secondary bloodstream infections. As mentioned above, three BSIs occurred within the 28-day period post-SCD-PED initiation, with none attributed to the device. Given that one culture was only positive for ~ 32 hours and the other two are generally considered to be common nosocomial infections, the lack of any unusual infections is reassuring and consistent with similar lack of any device-related infections from the SCD-PED-01 and − 02 registrational studies. Furthermore, there was no evidence of immunosuppression, in the form of opportunistic bacterial, viral or fungal infections, consistent with previous similar safety analyses from prior SCD clinical studies in patients with AKI requiring CKRT and a recent analysis of the effect of SCD treatment on neutrophil to lymphocyte ratios (NLR) from prior AKI studies.[ 11 ] , [ 12 ] Definitive conclusions will depend on the pre-specified comparison with a matched cohort from the WE-ROCK study, which will be conducted upon completion of the full enrollment target of 300 patients in the SAVE registry. Accordingly, the current safety data from these initial 21 patients should be regarded as preliminary and descriptive. Notably, many of these patients treated with SCD-PED therapy were critically ill, with nearly 1/4 receiving concomitant ECMO and 100% receiving vasoactive medications and invasive mechanical ventilation. The median PRISM III score at ICU admission was 15 with a range of complexities (PRISM III range of 0 to 31) and suggested patients with potentially higher severity than the SCD-PED clinical studies (PRISM II of 9.5)[ 9 ]. Importantly, almost half these children would not have been eligible for enrollment in the SCD-PED registrational clinical trials due to the severity of their illness or concomitant conditions, or to immune deficiencies or chronic immunosuppression (one patient had SLE and one patient had neutropenic sepsis[ 10 ]) (Supplementary Table 1). SCD-PED clinical use patterns were generally broad and ranged from early post-CKRT initiation starts to more advanced settings including salvage. In some cases, CKRT was initiated immediately upon admission to the ICU, followed with SCD-PED therapy within 24–48 hours (Supplementary Table 1; 3 patients were concurrently initiated on CKRT and SCD-PED therapy). Most patients only received one SCD-PED treatment course, with a median duration of 5 days. The treatment duration was similar to the registrational study duration of 6 days[ 9 ]. Importantly, patient survival rates were 76% at Day 28 and Day 60 with 71% still alive at Day 90, which is similar to those observed in the registrational studies and higher than the historical ppCRRT cohort of 50%. Ten out of 12 patients that survived to Day 90 were KRT-independent. The two patients who were still KRT dependent had complex chronic multi-organ inflammatory disease, with persistent pancreatitis and gastrointestinal perforation. Thus, they represented outliers, requiring at least four-fold greater SCD-PED therapy duration than the remainder of the cohort (23 and 36 days, respectively vs. cohort median of 5 days) (Supplementary Table 1). As such, they would have been excluded from the original clinical trials. It is important to note that SCD-PED therapy was terminated for these two patients as they achieved clinical stability to not require CKRT and were able to transition to intermittent hemodialysis. The findings from this initial cohort including registry patients demonstrate results consistent with the clinical trial experience which led to the initial HDE approval of the SCD, where a 77% 60-day survival was observed in pooled analysis from the SCD-PED-01 and SCD-PED-02 studies in patients with AKI requiring CKRT.[ 9 ] This post-approval cohort of 21 patients nearly doubles the overall pediatric experience with the SCD-PED to 43 patients. Furthermore, as prior reports on the SCD were limited to 60-day outcomes, this report is the first to present 90-day outcomes in either pediatric or adult patients with AKI requiring CKRT, especially within the context of real-world clinical evidence. We continue to interpret our outcome data with caution, as these data are primarily from an observational registry, so no efficacy claims can be made at this time. Yet, a 76% 60-day and 71% 90-day survival outcome in real-world clinical experience is generally favorable when considering the illness severity of the population, their co-morbid conditions, and the complexities of their treatment courses. Despite the small numbers (3 out of 5), the 60% survival outcomes in ECMO patients is also promising, given that none of the ECMO patients from the registrational SCD-PED-01 and − 02 studies survived.[ 9 ] This early cohort data now further expands evidence of SCD-PED in ECMO patients with AKI requiring CKRT. Similarly, a 75% survival in the four patients who were KRT dependent prior to treatment with SCD-PED at the Day 90 timepoint now provides evidence of the SCD’s potential utility in an unexplored subgroup of pediatric patients. Most importantly, no device-related adverse events or any other safety signals were reported with SCD-PED therapy, especially when considering that the early cohort patients were generally sicker and considerably more complex than the patients from the SCD-PED clinical studies.[ 7 ] We acknowledge several limitations to the current study. First, the outcomes described here are from a small set of patients, the majority of whom were from an observational registry and thus are subject to limitations typical of such sources, including data incompleteness. For example, certain clinical components of the PRISM III (such as Glasgow Coma Scale) and PELOD-2 indices were not available in some patients, resulting in a possible underestimation of their severity and organ status. Finally, the survival and KRT dependence outcomes presented are non-comparative and can only be considered as preliminary and descriptive. In summary, the first real-world experience of SCD-PED therapy in pediatric hospitals across the US demonstrate results consistent with the clinical trial experience in both safety and survival rates. We plan on performing comprehensive comparative outcomes analysis against a matched cohort from WE-ROCK upon completion of the enrollment target of the SAVE registry. Declarations Disclosures SLG is a paid consultant for SeaStar Medical and a member of the SeaStar Medical Scientific Advisory Board (SAB). RKB and DJA are members of the SeaStar Medical SAB. HDH has financial interests in SeaStar Medical. KAK, MH, SM, MSZ and SMG report no disclosures. ECS, DAC, SPNI, and KKC are all employees of SeaStar Medical. 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Nat Rev Nephrol 19:401–417 Goldstein SL, Somers MJ, Baum MA, Symons JM, Brophy PD, Blowey D, Bunchman TE, Baker C, Mottes T, McAfee N, Barnett J, Morrison G, Rogers K, Fortenberry JD (2005) Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int 67:653–658 Modem V, Thompson M, Gollhofer D, Dhar AV, Quigley R (2014) Timing of continuous renal replacement therapy and mortality in critically ill children*. Crit Care Med 42:943–953 Menon S, Krallman KA, Arikan AA, Fuhrman DY, Gorga SM, Mottes T, Ollberding N, Ricci Z, Stanski NL, Selewski DT, Soranno DE, Zappitelli M, Zang H, Gist KM, Investigators W-R (2023) Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK). Kidney Int Rep 8:1542–1552 Starr MC, Gist KM, Zang H, Ollberding NJ, Balani S, Cappoli A, Ciccia E, Joseph C, Kakajiwala A, Kessel A, Muff-Luett M, Santiago Lozano MJ, Pinto M, Reynaud S, Solomon S, Slagle C, Srivastava R, Shih WV, Webb T, Menon S (2024) Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease C Continuous Kidney Replacement Therapy and Survival in Children and Young Adults: Findings From the Multinational WE-ROCK Collaborative. Am J Kidney Dis 84:406–415 e401 Stanski NL, Gist KM, Hasson D, Stenson EK, Seo J, Ollberding NJ, Muff-Luett M, Cortina G, Alobaidi R, See E, Kaddourah A, Fuhrman DY (2024) Characteristics and Outcomes of Children and Young Adults With Sepsis Requiring Continuous Renal Replacement Therapy: A Comparative Analysis From the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK)*. Crit Care Med 52:1686–1699 Westover AJ, Humes HD, Pino CJ (2024) Immunomodulatory effects of a cell processing device to ameliorate dysregulated hyperinflammatory disease states. Sci Rep 14:12747 Goldstein SL, Ollberding NJ, Askenazi DJ, Basu RK, Selewski DT, Krallman KA, Yessayan L, Humes HD (2024) Selective Cytopheretic Device Use in Continuous Kidney Replacement Therapy in Children: A Cohort Study With a Historical Comparator. Kidney Med 6:100792 Humes HD, Luckritz K, Gorga S, Plomaritas K, Hoatlin S, Humes M, Yessayan L (2025) Management dilemma in choosing evolving treatments in neutropenic septic shock. Pediatr Nephrol Humes HD, Goldstein SL, Yessayan LT, Catanzaro DA, Scribe EC, Iyer SPN, Chung KK (2023) Safety Summary of the Selective Cytopheretic Device: A Review of Safety Data Across Multiple Clinical Trials in ICU Patients With Acute Kidney Injury and Multiple Organ Failure. Crit Care Explor 5:e0995 Iyer SPN, Ollberding NJ, Koyner JL, Yessayan LT, Chung KK, Humes HD (2025) The Impact of the Selective Cytopheretic Device on Neutrophil-to-Lymphocyte Ratios and Hematological Parameters in Acute Kidney Injury: A Pooled Analysis. Nephron:1–13 Supplementary Files SupplementalTable1.docx SupplementalTable2.docx SupplementalTable3.docx Cite Share Download PDF Status: Published Journal Publication published 06 Feb, 2026 Read the published version in Pediatric Nephrology → Version 1 posted Reviewers agreed at journal 09 Nov, 2025 Reviewers invited by journal 06 Nov, 2025 Editor assigned by journal 06 Nov, 2025 First submitted to journal 06 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7988526","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":541199794,"identity":"9196d783-8d0d-45ec-ab31-1c4dc5b54bbe","order_by":0,"name":"Stuart L. 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1","display":"","copyAsset":false,"role":"figure","size":631670,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Picture1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7988526/v1/4b9693c4d28aa3173416f733.jpg"},{"id":96363843,"identity":"269fee20-66e2-42b6-9c66-125aa3ee53fb","added_by":"auto","created_at":"2025-11-20 10:08:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":987477,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"Picture2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7988526/v1/2e01a5f39cf3e3858d96c77d.jpg"},{"id":102234636,"identity":"450c0cd3-46d2-4a40-9216-c612ba85565f","added_by":"auto","created_at":"2026-02-09 16:12:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2091015,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7988526/v1/1af80b46-1041-45ac-aa6a-969a3a8f6122.pdf"},{"id":96363732,"identity":"bf792459-8e9a-452b-8d31-f422a895dbbb","added_by":"auto","created_at":"2025-11-20 10:07:51","extension":"docx","order_by":7,"title":"","display":"","copyAsset":false,"role":"supplement","size":44717,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-7988526/v1/d897d0520af3105932f91a14.docx"},{"id":96270229,"identity":"82b4efa4-acb5-42ec-a646-848683329a0d","added_by":"auto","created_at":"2025-11-19 09:15:43","extension":"docx","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":27549,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable2.docx","url":"https://assets-eu.researchsquare.com/files/rs-7988526/v1/2336f19a4c70258f9262c539.docx"},{"id":96270230,"identity":"e1b3c77d-412f-451f-ab01-c0b5b311c749","added_by":"auto","created_at":"2025-11-19 09:15:43","extension":"docx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":39264,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementalTable3.docx","url":"https://assets-eu.researchsquare.com/files/rs-7988526/v1/f3047968907f616b0e2138cf.docx"}],"financialInterests":"","formattedTitle":"Early Post-Approval Experience of The Selective Cytopheretic Device Surveillance Registry for Pediatric AKI Requiring Kidney Replacement Therapy","fulltext":[{"header":"Background","content":"\u003cp\u003eAcute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT) is a serious and often life-threatening condition in pediatric patients, particularly those with concomitant sepsis or a septic-like condition. Sepsis associated AKI is characterized by a dysregulated immune response, systemic inflammation, and endothelial dysfunction, all of which contribute to the historically poor outcomes observed in this population.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Current therapeutic strategies for managing pediatric sepsis-associated AKI remain limited and are supportive in nature, necessitating innovative approaches to enhance patient survival.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eIn a multicenter study from the prospective pediatric CKRT (ppCRRT) registry of 116 children with multiorgan dysfunction (MOD) receiving CKRT including 47 (39%) with sepsis, ICU survival was 51.7%.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] A recent single-center study of children receiving CKRT revealed a similar survival rate in 130 patients receiving a vasoactive medication (50.0%) or mechanical ventilation (50.7%) on CKRT.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] A recent multicenter (32 centers, 7 countries) study from the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Diseases (WE-ROCK) of 980 patients (Birth- 25 years of age) who received CKRT for AKI or pathologic fluid accumulation reported 64.1% survival to ICU discharge.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] A secondary analysis from the same cohort showed patients with sepsis at CKRT initiation were less likely to liberate from CKRT by 28 days (30% vs. 38%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and had higher mortality rates (47% vs. 31%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared to non-septic patients.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe selective cytopheretic device for pediatrics (SCD-PED) represents a potential breakthrough in the management of patients with sepsis associated AKI requiring CKRT. The SCD-PED is a novel cell-directed immunomodulatory therapy that is connected in series to a commercially available CKRT circuit, and in the presence of regional citrate anticoagulation, it modulates inflammation by targeting pro-inflammatory neutrophils and monocytes to shift them to a lower inflammatory phenotype.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] The resulting physiological consequences are abatement of the hyperinflammatory milieu, a return to immune homeostasis and restoration of organ function within the patient.\u003c/p\u003e\u003cp\u003ePooled analysis from two prospective multicenter studies (n\u0026thinsp;=\u0026thinsp;22 children with AKI requiring CKRT and MOD weighing\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;10 kg) demonstrated a 77% survival rate, with no device-related serious adverse events observed.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] Importantly, none of the survivors were dialysis-dependent at 60 days, and 87.5% had recovered normal kidney function. Based on these findings, the SCD-PED (\u003cem\u003eQUELIMMUNE\u0026trade;\u003c/em\u003e, SeaStar Medical, Denver, CO) received Humanitarian Device Exemption (HDE) approval from United States Food and Drug Administration for use in critically ill children\u0026thinsp;\u0026ge;\u0026thinsp;10 kg with AKI accompanied by sepsis or septic conditions receiving antibiotics and requiring CKRT. As part of this approval, FDA required a post-approval surveillance registry to collect additional safety data prospectively among all patients treated with the device under the HDE. We report the study design of the \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eS\u003c/span\u003eCD-PED Pedi\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eA\u003c/span\u003etric Sur\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eV\u003c/span\u003eeillance R\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eE\u003c/span\u003egistry, (SAVE Registry) and preliminary results from the first 21 patients treated post-approval, including those in SAVE.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe SAVE Registry (ClinicalTrials.gov identifier: NCT06517810; Primary IRB: Cincinnati Children\u0026rsquo;s Hospital: 2024\u0026thinsp;\u0026minus;\u0026thinsp;0153; 25-April-2024) is a mandatory, prospective, post-approval surveillance registry with a primary objective to collect descriptive safety data on the clinical use of the SCD-PED under the HDE. We anticipate approximately 50 participating institutions in the United States will enroll up to 300 patients in the registry. Each patient treated with SCD-PED therapy according to its FDA-approved indication under the HDE will be enrolled in the registry. All enrolled patients will receive the standard of care ICU treatment for those undergoing CKRT. There are no specific exclusion criteria for the registry. Additionally, patients treated with the SCD-PED under Expanded Access will be included in the registry, if informed consent is obtained. Informed consent/assent for the registry is mandatory prior to therapy. The treatment period (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) begins when the patient starts SCD-PED therapy and will continue until therapy completion. Therapy completion is defined as \u0026gt;\u0026thinsp;72 hours without re-initiation of SCD-PED therapy. In contrast to the SCD-PED clinical studies, where the treatment duration was limited to \u0026le;\u0026thinsp;10 days, the treatment duration will be determined by the clinical team and can exceed 10 days. Follow-up will continue out to 90 days.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAt baseline, demographic data, hospitalization data and CKRT data will be collected (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). During the treatment period, CKRT parameters, SCD-PED performance, adverse events of special interest, and other parameters will be collected.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe primary outcome is a new (secondary) blood stream infection (BSI) in the first 28 days after SCD-PED initiation or through hospital discharge, whichever is sooner. A matched cohort of CKRT patients with sepsis who did not receive treatment with SCD-PED from the WE-ROCK registry\u003csup\u003e3\u003c/sup\u003e will serve as controls. Additional outcomes (see Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) collected at Day 28 include patient survival status, hospitalization status, kidney replacement therapy status, cardiorespiratory support, most recent serum creatinine, adverse events, and events of interest. An additional follow up at Day 90 is being performed to match the WE-ROCK dataset for patient status, hospitalization status, kidney replacement therapy status, and most recent serum creatinine.\u003c/p\u003e\u003cp\u003eAn independent data and safety monitoring board (DSMB), composed of 2 clinicians and a biostatistician, will regularly review safety data throughout the registry in accordance with FDA guidance. The board will assess adverse events, bloodstream infections, and deaths, meeting at least quarterly and ad hoc as needed. To support objective oversight, the DSMB operates under a formal charter and has already established data review protocols.\u003c/p\u003e\u003cp\u003eInitial post-approval outcomes analysis included patients enrolled in SAVE, as well patients treated under emergency use post-approval who could not be included into the registry.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe SAVE Surveillance Registry was initiated in July 2024 and preliminary outcomes data are available from 20 patients across five registry sites. Of the 20 patients, two patients were treated under emergency use due to not meeting the HDE indication criteria. One patient exceeded the upper age limit of 22 years, and the other had a body weight below 10 kg. Following treatment, both individuals were subsequently included in the registry to facilitate the collection of safety and outcome data. One additional patient was treated under emergency use at a 6th site and was recently published as a case report,[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] but could not be included in SAVE due to lack of informed consent for the registry. However, since this episode occurred after HDE approval, data from this case are included for this analysis, resulting in a total of 21 patients available for early outcome analysis. Treated patients were critically ill with AKI or acute kidney worsening requiring CKRT, had sepsis, and a variety of severe underlying illnesses with significant complexities, including those with malignancies, history of kidney transplant and/or ESRD, chronic immunosuppression or immunodeficiencies, and open wounds (see Supplementary Table\u0026nbsp;1 for individual patient characteristics and hospital/ICU diagnoses). Unless otherwise noted, all metrics refer to the cohort of 21 patients. Median age at ICU admission was 9.2 years (interquartile range [IQR]: 5.3,16.8; range 1.1\u0026ndash;23.7; n\u0026thinsp;=\u0026thinsp;21), and median weight was 21.5 kg (IQR: 16.5, 45.1; range 9-105; n\u0026thinsp;=\u0026thinsp;17) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The cohort was 47% White, 19% Hispanic, 10% Black, 5% Asian/Pacific Islander, with 19% of other/unknown background. Median PRISM III score at ICU admission was 15 (IQR: 8, 22; range 0\u0026ndash;31). At the time of SCD-PED initiation, median PELOD-2 score was 9 (IQR: 6, 11; range 3\u0026ndash;15) and all patients were receiving vasoactive medications and mechanical ventilation. Nearly 20% of patients (4 / 21) had a history of ESRD and/or kidney transplant and were KRT dependent prior to treatment (Supplementary Table\u0026nbsp;2) and 33% (7 / 21) had receipt of extracorporeal membrane oxygenation (ECMO) either concomitantly (n\u0026thinsp;=\u0026thinsp;5) with or immediately prior (n\u0026thinsp;=\u0026thinsp;2) to treatment with SCD-PED. The median number of SCD treatment courses was 1 (IQR: 1, 1; range 1\u0026ndash;3), and the median total duration of therapy (DoT) was 5 days (IQR: 2,10; range 1\u0026ndash;33). The median days from CKRT to SCD-PED initiation was 2 (IQR: 0, 4; range 0, 97), with 6 patients initiated within a 24-hour period (median of 4.5 hours [IQR: 0, 15.35; range 0, 19.8]). The SCD-PED devices were switched out every 24 hours per protocol throughout the treatment course.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatient Demographics \u0026amp; Baseline Details\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCategory (N = # of patients with data reported)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eResults\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients Enrolled\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian (IQR) Age, years (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.2 (5.3, 16.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian (IQR) Weight, kg (N\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21.5 (16.5, 45.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian (IQR) Height, cm (N\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e113 (99.8, 152.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (Male / Female) (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11/10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian (IQR) PRISM III Score at ICU admission (N\u0026thinsp;=\u0026thinsp;19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (8, 22)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian (IQR) PELOD-2 Score at SCD-PED initiation (N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (6, 11)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReceipt of Vasoactive Medications (%) (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (100)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntensive Mechanical Ventilation (%) (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (100)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eReceived Extracorporeal Membrane Oxygenation (N\u0026thinsp;=\u0026thinsp;19)\u003c/span\u003e:\u003c/p\u003e\u003cp\u003eConcurrently with SCD-PED, n (%)\u003c/p\u003e\u003cp\u003ePrior to SCD-PED, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (25)\u003c/p\u003e\u003cp\u003e2 (10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedHx of ESRD and/or Recent Kidney Transplant Prior to Treatment (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (20)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian (IQR) Days from ICU to CKRT (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (0, 18)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian (IQR) Days from CKRT to SCD-PED Start (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (0, 4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian (IQR) SCD-PED Treatment Days (per course) (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (2, 10)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian (IQR) SCD-PED Treatment Course (N\u0026thinsp;=\u0026thinsp;21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (1,1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eCKRT, continuous kidney replacement therapy; ESRD, end-stage renal disease; ICU, intensive care unit; IQR, interquartile range; MedHx, medical history; PELOD-2, pediatric logistic organ dysfunction-2 score; PRISM III, pediatric risk of mortality score; SCD-PED, selective cytopheretic device for pediatrics\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eOutcomes data were available for all 21 patients at the time of this analysis (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Three patients had positive blood cultures at 6, 7, and 22 days after the termination of SCD-PED therapy. One culture was positive (ampicillin-resistant \u003cem\u003eKlebsiella\u003c/em\u003e) for ~\u0026thinsp;32 hours and was negative the following day, while the other two cultures were positive for \u003cem\u003eEnterococcus\u003c/em\u003e and \u003cem\u003eEnterobacter\u003c/em\u003e. All infections were deemed unrelated to SCD-PED by the treating clinician and the DSMB. Additionally, there were no device-related adverse events reported, including no reports of immunosuppressive effects (e.g., leukopenia or neutropenia). Sixteen (76%) of 21 patients survived through the Treatment Period, Day 28, and Day 60. Three patients died while receiving SCD-PED therapy. Fifteen (71%) of 21 patients survived through Day 90. Three of 5 patients concomitantly treated with SCD-PED and ECMO survived to Day 90. Among the survivors who were not KRT dependent prior to treatment, 9 out of 12 (75%) and 10 out of 12 (83%) patients were KRT independent at Day 28 and Day 90, respectively. Individual Day 28, 60, 90, and KRT patient outcomes are listed in Supplementary Table\u0026nbsp;3.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePreliminary Results\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCategory\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eResults\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePatients Enrolled\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDevice-Related Events\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePositive Blood Cultures\u003c/span\u003e:\u003c/p\u003e\u003cp\u003eDuring Treatment Period\u003c/p\u003e\u003cp\u003eDuring Follow-up Period (28 days post-initiation)\u003c/p\u003e\u003cp\u003eDeemed as Related to SCD-PED by DSMB and PI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eSurvival\u003c/span\u003e:\u003c/p\u003e\u003cp\u003eDay 28, n (%)\u003c/p\u003e\u003cp\u003eDay 60, n (%)\u003c/p\u003e\u003cp\u003eDay 90, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eAll Patients\u003c/span\u003e\u003c/p\u003e\u003cp\u003e16/21 (76)\u003c/p\u003e\u003cp\u003e16/21 (76)\u003c/p\u003e\u003cp\u003e15/21 (71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eECMO only\u003c/span\u003e\u003csup\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026dagger;\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003e3/5 (60)\u003c/p\u003e\u003cp\u003e3/5 (60)\u003c/p\u003e\u003cp\u003e3/5 (60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eHx ESRD/Tx\u003c/span\u003e\u003csup\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026Dagger;\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003e4/4 (100)\u003c/p\u003e\u003cp\u003e4/4 (100)\u003c/p\u003e\u003cp\u003e3/4 (75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eKRT Independence Among Survivors\u003c/span\u003e:\u003c/p\u003e\u003cp\u003eDay 28, n (%)\u003c/p\u003e\u003cp\u003eDay 90, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003e9/12 (75)\u003c/p\u003e\u003cp\u003e10/12 (83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e\u003cp\u003e\u003csup\u003e\u0026dagger;\u003c/sup\u003e5 patients with concomitantly treated with SCD-PED and ECMO;\u003csup\u003e\u0026Dagger;\u003c/sup\u003e4 patients were KRT-dependent prior to SCD-PED therapy; of these, 4 patients at Day 28 and 3 at Day 90 were excluded for the KRT is outcome as they were KRT-dependent prior to SCD-PED treatment.\u003c/p\u003e\u003cp\u003eDSMB, data safety monitoring board; ECMO, extracorporeal membrane oxygenation; ESRD, end-stage renal disease; Hx, medical history; PI, principal investigator; KRT, renal replacement therapy; SCD-PED, selective cytopheretic device for pediatrics; Tx, kidney transplant.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003ePediatric AKI requiring CKRT in the setting of sepsis and/or MOD continues to result in significant morbidity and mortality. Here we report the first real-world clinical experience of SCD-PED therapy in this critically ill pediatric population including patients from the FDA-mandated SAVE registry as part of the HDE. The HDE approval of SCD-PED (\u003cem\u003eQUELIMMUNE\u0026trade;\u003c/em\u003e) for pediatric sepsis-associated AKI requiring CKRT was based on safety and probable benefit demonstrated in a cohort of 22 patients. Because the approval of SCD-PED was predicated on a relatively small patient population, FDA mandated the implementation of a post-market registry to monitor the safety profile of the device, especially as it relates to secondary bloodstream infections. As mentioned above, three BSIs occurred within the 28-day period post-SCD-PED initiation, with none attributed to the device. Given that one culture was only positive for ~\u0026thinsp;32 hours and the other two are generally considered to be common nosocomial infections, the lack of any unusual infections is reassuring and consistent with similar lack of any device-related infections from the SCD-PED-01 and \u0026minus;\u0026thinsp;02 registrational studies. Furthermore, there was no evidence of immunosuppression, in the form of opportunistic bacterial, viral or fungal infections, consistent with previous similar safety analyses from prior SCD clinical studies in patients with AKI requiring CKRT and a recent analysis of the effect of SCD treatment on neutrophil to lymphocyte ratios (NLR) from prior AKI studies.[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003csup\u003e,\u003c/sup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Definitive conclusions will depend on the pre-specified comparison with a matched cohort from the WE-ROCK study, which will be conducted upon completion of the full enrollment target of 300 patients in the SAVE registry. Accordingly, the current safety data from these initial 21 patients should be regarded as preliminary and descriptive.\u003c/p\u003e\u003cp\u003eNotably, many of these patients treated with SCD-PED therapy were critically ill, with nearly 1/4 receiving concomitant ECMO and 100% receiving vasoactive medications and invasive mechanical ventilation. The median PRISM III score at ICU admission was 15 with a range of complexities (PRISM III range of 0 to 31) and suggested patients with potentially higher severity than the SCD-PED clinical studies (PRISM II of 9.5)[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Importantly, almost half these children would not have been eligible for enrollment in the SCD-PED registrational clinical trials due to the severity of their illness or concomitant conditions, or to immune deficiencies or chronic immunosuppression (one patient had SLE and one patient had neutropenic sepsis[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]) (Supplementary Table\u0026nbsp;1). SCD-PED clinical use patterns were generally broad and ranged from early post-CKRT initiation starts to more advanced settings including salvage. In some cases, CKRT was initiated immediately upon admission to the ICU, followed with SCD-PED therapy within 24\u0026ndash;48 hours (Supplementary Table\u0026nbsp;1; 3 patients were concurrently initiated on CKRT and SCD-PED therapy). Most patients only received one SCD-PED treatment course, with a median duration of 5 days. The treatment duration was similar to the registrational study duration of 6 days[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Importantly, patient survival rates were 76% at Day 28 and Day 60 with 71% still alive at Day 90, which is similar to those observed in the registrational studies and higher than the historical ppCRRT cohort of 50%. Ten out of 12 patients that survived to Day 90 were KRT-independent. The two patients who were still KRT dependent had complex chronic multi-organ inflammatory disease, with persistent pancreatitis and gastrointestinal perforation. Thus, they represented outliers, requiring at least four-fold greater SCD-PED therapy duration than the remainder of the cohort (23 and 36 days, respectively \u003cem\u003evs.\u003c/em\u003e cohort median of 5 days) (Supplementary Table\u0026nbsp;1). As such, they would have been excluded from the original clinical trials. It is important to note that SCD-PED therapy was terminated for these two patients as they achieved clinical stability to not require CKRT and were able to transition to intermittent hemodialysis.\u003c/p\u003e\u003cp\u003eThe findings from this initial cohort including registry patients demonstrate results consistent with the clinical trial experience which led to the initial HDE approval of the SCD, where a 77% 60-day survival was observed in pooled analysis from the SCD-PED-01 and SCD-PED-02 studies in patients with AKI requiring CKRT.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] This post-approval cohort of 21 patients nearly doubles the overall pediatric experience with the SCD-PED to 43 patients. Furthermore, as prior reports on the SCD were limited to 60-day outcomes, this report is the first to present 90-day outcomes in either pediatric or adult patients with AKI requiring CKRT, especially within the context of real-world clinical evidence. We continue to interpret our outcome data with caution, as these data are primarily from an observational registry, so no efficacy claims can be made at this time. Yet, a 76% 60-day and 71% 90-day survival outcome in real-world clinical experience is generally favorable when considering the illness severity of the population, their co-morbid conditions, and the complexities of their treatment courses. Despite the small numbers (3 out of 5), the 60% survival outcomes in ECMO patients is also promising, given that none of the ECMO patients from the registrational SCD-PED-01 and \u0026minus;\u0026thinsp;02 studies survived.[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] This early cohort data now further expands evidence of SCD-PED in ECMO patients with AKI requiring CKRT. Similarly, a 75% survival in the four patients who were KRT dependent prior to treatment with SCD-PED at the Day 90 timepoint now provides evidence of the SCD\u0026rsquo;s potential utility in an unexplored subgroup of pediatric patients. Most importantly, no device-related adverse events or any other safety signals were reported with SCD-PED therapy, especially when considering that the early cohort patients were generally sicker and considerably more complex than the patients from the SCD-PED clinical studies.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eWe acknowledge several limitations to the current study. First, the outcomes described here are from a small set of patients, the majority of whom were from an observational registry and thus are subject to limitations typical of such sources, including data incompleteness. For example, certain clinical components of the PRISM III (such as Glasgow Coma Scale) and PELOD-2 indices were not available in some patients, resulting in a possible underestimation of their severity and organ status. Finally, the survival and KRT dependence outcomes presented are non-comparative and can only be considered as preliminary and descriptive.\u003c/p\u003e\u003cp\u003eIn summary, the first real-world experience of SCD-PED therapy in pediatric hospitals across the US demonstrate results consistent with the clinical trial experience in both safety and survival rates. We plan on performing comprehensive comparative outcomes analysis against a matched cohort from WE-ROCK upon completion of the enrollment target of the SAVE registry.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eDisclosures\u003c/h2\u003e\u003cp\u003e SLG is a paid consultant for SeaStar Medical and a member of the SeaStar Medical Scientific Advisory Board (SAB). RKB and DJA are members of the SeaStar Medical SAB. HDH has financial interests in SeaStar Medical. KAK, MH, SM, MSZ and SMG report no disclosures. ECS, DAC, SPNI, and KKC are all employees of SeaStar Medical.\u003c/p\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFuhrman DY, Stanski NL, Krawczeski CD, Greenberg JH, Arikan AAA, Basu RK, Goldstein SL, Gist KM (2024) workgroup A A proposed framework for advancing acute kidney injury risk stratification and diagnosis in children: a report from the 26th Acute Disease Quality Initiative (ADQI) conference. Pediatr Nephrol 39:929\u0026ndash;939\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZarbock A, Nadim MK, Pickkers P, Gomez H, Bell S, Joannidis M, Kashani K, Koyner JL, Pannu N, Meersch M, Reis T, Rimmele T, Bagshaw SM, Bellomo R, Cantaluppi V, Deep A, De Rosa S, Perez-Fernandez X, Husain-Syed F, Kane-Gill SL, Kelly Y, Mehta RL, Murray PT, Ostermann M, Prowle J, Ricci Z, See EJ, Schneider A, Soranno DE, Tolwani A, Villa G, Ronco C, Forni LG (2023) Sepsis-associated acute kidney injury: consensus report of the 28th Acute Disease Quality Initiative workgroup. Nat Rev Nephrol 19:401\u0026ndash;417\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoldstein SL, Somers MJ, Baum MA, Symons JM, Brophy PD, Blowey D, Bunchman TE, Baker C, Mottes T, McAfee N, Barnett J, Morrison G, Rogers K, Fortenberry JD (2005) Pediatric patients with multi-organ dysfunction syndrome receiving continuous renal replacement therapy. Kidney Int 67:653\u0026ndash;658\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eModem V, Thompson M, Gollhofer D, Dhar AV, Quigley R (2014) Timing of continuous renal replacement therapy and mortality in critically ill children*. Crit Care Med 42:943\u0026ndash;953\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMenon S, Krallman KA, Arikan AA, Fuhrman DY, Gorga SM, Mottes T, Ollberding N, Ricci Z, Stanski NL, Selewski DT, Soranno DE, Zappitelli M, Zang H, Gist KM, Investigators W-R (2023) Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK). Kidney Int Rep 8:1542\u0026ndash;1552\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStarr MC, Gist KM, Zang H, Ollberding NJ, Balani S, Cappoli A, Ciccia E, Joseph C, Kakajiwala A, Kessel A, Muff-Luett M, Santiago Lozano MJ, Pinto M, Reynaud S, Solomon S, Slagle C, Srivastava R, Shih WV, Webb T, Menon S (2024) Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease C Continuous Kidney Replacement Therapy and Survival in Children and Young Adults: Findings From the Multinational WE-ROCK Collaborative. Am J Kidney Dis 84:406\u0026ndash;415 e401\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStanski NL, Gist KM, Hasson D, Stenson EK, Seo J, Ollberding NJ, Muff-Luett M, Cortina G, Alobaidi R, See E, Kaddourah A, Fuhrman DY (2024) Characteristics and Outcomes of Children and Young Adults With Sepsis Requiring Continuous Renal Replacement Therapy: A Comparative Analysis From the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK)*. Crit Care Med 52:1686\u0026ndash;1699\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWestover AJ, Humes HD, Pino CJ (2024) Immunomodulatory effects of a cell processing device to ameliorate dysregulated hyperinflammatory disease states. Sci Rep 14:12747\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoldstein SL, Ollberding NJ, Askenazi DJ, Basu RK, Selewski DT, Krallman KA, Yessayan L, Humes HD (2024) Selective Cytopheretic Device Use in Continuous Kidney Replacement Therapy in Children: A Cohort Study With a Historical Comparator. Kidney Med 6:100792\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHumes HD, Luckritz K, Gorga S, Plomaritas K, Hoatlin S, Humes M, Yessayan L (2025) Management dilemma in choosing evolving treatments in neutropenic septic shock. Pediatr Nephrol\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHumes HD, Goldstein SL, Yessayan LT, Catanzaro DA, Scribe EC, Iyer SPN, Chung KK (2023) Safety Summary of the Selective Cytopheretic Device: A Review of Safety Data Across Multiple Clinical Trials in ICU Patients With Acute Kidney Injury and Multiple Organ Failure. Crit Care Explor 5:e0995\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIyer SPN, Ollberding NJ, Koyner JL, Yessayan LT, Chung KK, Humes HD (2025) The Impact of the Selective Cytopheretic Device on Neutrophil-to-Lymphocyte Ratios and Hematological Parameters in Acute Kidney Injury: A Pooled Analysis. Nephron:1\u0026ndash;13\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"SCD, selective cytopheretic device, immunomodulation, acute kidney injury, kidney replacement therapy, sepsis","lastPublishedDoi":"10.21203/rs.3.rs-7988526/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7988526/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eThe selective cytopheretic device for pediatrics (SCD-PED) was granted a Humanitarian Device Exemption (HDE) in 2024 by United States Food and Drug Administration (FDA) for treatment of critically ill children weighing\u0026thinsp;\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003e\u0026ge;\u003c/span\u003e\u0026thinsp;10 kilograms with AKI due to sepsis or a septic condition on antibiotics and requiring CKRT. FDA required a post-approval surveillance registry to collect additional safety data among all patients treated with SCD-PED under the HDE as part of the approval.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eS\u003c/span\u003eCD-PED Pedi\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eA\u003c/span\u003etric Sur\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eV\u003c/span\u003eeillance R\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eE\u003c/span\u003egistry (SAVE; NCT06517810) will enroll up to 300 patients initiated on SCD-PED therapy under the HDE-approved indication. The primary outcome is a new (secondary) blood stream infection in the first 28 days after SCD-PED initiation. Additional Day 28 and Day 90 clinical outcomes including mortality and KRT requirement will be collected.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eRegistry design and preliminary outcomes from the first 21 patients are reported. Three new positive blood cultures were observed during the follow-up period after cessation of SCD-PED therapy, all of which were deemed unrelated to SCD. Sixteen (76%) and 15 (71%) of 21 patients survived through to Day 60, and 90, respectively. Three patients died while receiving SCD-PED therapy. No device-related adverse events were reported.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eThis initial real-world experience of SCD-PED therapy in pediatric AKI with sepsis in patients requiring CKRT suggests no device-related infections and similar improved clinical outcomes consistent with the previous trial SCD-PED experience in this critically ill population.\u003c/p\u003e","manuscriptTitle":"Early Post-Approval Experience of The Selective Cytopheretic Device Surveillance Registry for Pediatric AKI Requiring Kidney Replacement Therapy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-19 09:15:39","doi":"10.21203/rs.3.rs-7988526/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2025-11-09T08:47:20+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-06T20:58:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-06T17:11:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Nephrology","date":"2025-11-06T11:53:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pnep","sideBox":"Learn more about [Pediatric Nephrology](http://link.springer.com/journal/467)","snPcode":"467","submissionUrl":"https://www.editorialmanager.com/pnep/default2.aspx","title":"Pediatric Nephrology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7ce6adbe-61b9-4575-a65a-c3d78521070d","owner":[],"postedDate":"November 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:08:51+00:00","versionOfRecord":{"articleIdentity":"rs-7988526","link":"https://doi.org/10.1007/s00467-026-07181-1","journal":{"identity":"pediatric-nephrology","isVorOnly":false,"title":"Pediatric Nephrology"},"publishedOn":"2026-02-06 15:58:17","publishedOnDateReadable":"February 6th, 2026"},"versionCreatedAt":"2025-11-19 09:15:39","video":"","vorDoi":"10.1007/s00467-026-07181-1","vorDoiUrl":"https://doi.org/10.1007/s00467-026-07181-1","workflowStages":[]},"version":"v1","identity":"rs-7988526","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7988526","identity":"rs-7988526","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}