Division of Nephrology, Department of Internal Medicine, University of Michigan Ann Arbor, Ann Arbor, MI, USA.
Innovative Biotherapies, Ann Arbor, MI, USA.
Pediatr Res. 2023 Jan;93(1):89-96. doi: 10.1038/s41390-022-02061-4. Epub 2022 May 2.
Application of the immunomodulatory selective cytopheretic device (SCD) to enhance renal replacement therapy and improve outcomes of acute kidney injury in pediatric patients is impeded by safety concerns. Therapy using a pediatric hemodialysis system could overcome these limitations.
Yucatan minipigs (8-15 kg) with induced septic shock underwent continuous hemodiafiltration with the CARPEDIEM™ pediatric hemodialysis system using regional citrate anticoagulation (RCA) with or without SCD (n = 5 per group). Circuit function plus hemodynamic and hematologic parameters were assessed for 6 h.
SCD was readily integrated into the CARPEDIEM™ system and treatment delivered for 6 h without interference with pump operation. SCD-treated pigs maintained higher blood pressure (p = 0.009) commensurate with lesser degree of lactic acidosis (p = 0.008) compared to pigs only receiving hemodiafiltration. Renal failure occurred in untreated pigs while urine output was sustained with SCD therapy. Neutrophil activation levels and ss-SOFA scores at 6 h trended lower in the SCD-treated cohort.
SCD therapy under RCA was safely administered using the CARPEDIEM™ pediatric hemodialysis system for up to 6 h and no circuit compatibility issues were identified. Sepsis progression and organ dysfunction was diminished with SCD treatment in this model supportive of therapeutic benefit of this immunomodulatory therapy.
SCD therapy with regional citrate anticoagulation has the potential to be administered safely to patients weighing <20 kg using the Carpediem renal replacement therapy platform. Use of a renal replacement therapy platform designed specifically for neonates/infants overcomes safety concerns for delivery of SCD treatment in this population. SCD therapy using the Carpediem renal replacement therapy platform retained the suggestive efficacy seen in larger children and adults to reduce organ injury and dysfunction from sepsis.
免疫调节选择性细胞分离装置（SCD）的应用可增强肾脏替代治疗并改善儿科急性肾损伤患者的预后，但由于安全性问题，其在儿科患者中的应用受到阻碍。使用儿科血液透析系统进行治疗可能克服这些限制。
诱导脓毒症休克的尤卡坦小型猪（8-15kg）接受连续血液透析滤过治疗，使用 CARPEDIEM™儿科血液透析系统，采用局部枸橼酸抗凝（RCA）联合或不联合 SCD（每组 5 只）。评估 6 小时的回路功能、血流动力学和血液学参数。
SCD 可轻松集成到 CARPEDIEM™系统中，且在不干扰泵操作的情况下，可在 6 小时内进行治疗。与仅接受血液透析滤过治疗的猪相比，接受 SCD 治疗的猪血压更高（p=0.009），酸中毒程度更低（p=0.008）。未接受治疗的猪出现肾功能衰竭，而 SCD 治疗组的尿量持续。SCD 治疗组的中性粒细胞活化水平和 6 小时时的 ss-SOFA 评分呈下降趋势。
在 RCA 下使用 CARPEDIEM™儿科血液透析系统，SCD 治疗可安全进行长达 6 小时，且未发现回路兼容性问题。在该模型中，SCD 治疗可减轻脓毒症进展和器官功能障碍，支持这种免疫调节治疗的治疗益处。
使用局部枸橼酸抗凝的 SCD 治疗具有在体重<20kg 的患者中安全应用的潜力，使用专门为新生儿/婴儿设计的肾脏替代治疗平台可以克服在该人群中应用 SCD 治疗的安全性问题。CARPEDIEM 肾脏替代治疗平台上的 SCD 治疗保留了在较大儿童和成人中观察到的有希望的疗效，可减轻脓毒症引起的器官损伤和功能障碍。
