Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs.
Immunomodulatory therapy using a pediatric dialysis system ameliorates septic shock in miniature pigs.
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DOI：
10.1038/s41390-022-02061-4
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发表时间：
2023-01
影响因子：
3.6
通讯作者：
Humes, H. David
中科院分区：
文献类型：
--
作者：
Johnston, Kimberly A.;Pino, Christopher J.;Chan, Goldia;Ketteler, Skylar K.;Goldstein, Stuart L.;Humes, H. David
安全性问题阻碍了免疫调节性选择性细胞移植装置（SCD）在儿科患者中用于增强肾脏替代治疗和改善急性肾损伤结局的应用。使用儿科血液透析系统的治疗可以克服这些局限性。诱导感染性休克的尤卡坦小型猪（8- 15 kg）使用CARPEDIEM儿科血液透析系统进行连续血液透析滤过，使用局部柠檬酸盐抗凝（RCA），伴或不伴SCD（每组n=5）。6 h后评估循环功能、血流动力学和血液学参数。SCD很容易集成到CARPEDIEM™系统中，治疗持续6小时，不会干扰泵的运行。与仅接受血液透析滤过的猪相比，SCD处理的猪保持较高的血压（p=0.009），与较低程度的乳酸酸中毒（p=0.008）相称。未处理猪发生肾衰竭，而SCD治疗可维持尿量。SCD治疗队列中6小时时的神经元活化水平和ssSOFA评分呈降低趋势。使用CARPEDIEM™小儿血液透析系统在RCA下安全进行SCD治疗长达6小时，未发现回路兼容性问题。在该模型中，SCD治疗减少了脓毒症进展和器官功能障碍，支持了该免疫调节治疗的治疗获益。
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 (8–15kg) 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 6h. SCD was readily integrated into the CARPEDIEM™ system and treatment delivered for 6 hours 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 ssSOFA scores at 6 hour trended lower in the SCD treated cohort. SCD therapy under RCA was safely administered using the CARPEDIEM™ pediatric hemodialysis system for up to 6 hours 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.
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DOI：
10.1056/nejmoa1611391
发表时间：
2017-01-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Kaddourah A;Basu RK;Bagshaw SM;Goldstein SL;AWARE Investigators
通讯作者：
AWARE Investigators
影响因子：
120.7
作者：
Zarbock, Alexander;Kullmar, Mira;Meersch, Melanie
通讯作者：
Meersch, Melanie
影响因子：
1.6
作者：
Tumlin, James A.;Chawla, Lakhmir;Humes, H. David
通讯作者：
Humes, H. David
影响因子：
6
作者：
Pino CJ;Westover AJ;Johnston KA;Buffington DA;Humes HD
通讯作者：
Humes HD
影响因子：
3.7
作者：
Ding F;Song JH;Jung JY;Lou L;Wang M;Charles L;Westover A;Smith PL;Pino CJ;Buffington DA;Humes HD
通讯作者：
Humes HD