Innovative BioTherapies, Inc., Ann Arbor, MI, USA.
Artif Organs. 2013 Feb;37(2):203-10. doi: 10.1111/j.1525-1594.2012.01541.x. Epub 2012 Oct 16.
Selective cytopheretic inhibitory device (SCD) therapy is an immunomodulatory treatment provided by a synthetic biomimetic membrane in an extracorporeal circuit, which has shown promise in preclinical large animal models of severe sepsis as well as in clinical trials treating patients with acute kidney injury and multiple organ failure. During SCD therapy, citrate is administered to lower ionized calcium levels in blood for anticoagulation and inhibition of leukocyte activation. Historically, citrate has been known to interfere with sorbent dialysis, therefore, posing a potential issue for the use of SCD therapy with a portable dialysis system. This sorbent dialysis SCD (sorbent SCD) would be well suited for battlefield and natural disaster applications where the water supply for standard dialysis is limited, and the types of injuries in those settings would benefit from SCD therapy. In order to explore the compatibility of sorbent and SCD technologies, a uremic porcine model was tested with the Allient sorbent dialysis system (Renal Solutions Incorporated, Fresenius Medical Care, Warrendale, PA, USA) and concurrent SCD therapy with regional citrate anticoagulation. The hypothesis to be assessed was whether the citrate load required by the SCD could be metabolized prior to recirculation from systemic blood back into the therapeutic circuit. Despite the fact that the sorbent SCD maintained urea clearance without any adverse hematologic events, citrate load for SCD therapy caused an interaction with the sorbent column resulting in elevated, potentially toxic aluminum levels in dialysate and in systemic blood. Alternative strategies to implement sorbent-SCD therapy will be required, including development of alternate urease-sorbent column binding chemistry or further changes to the sorbent-SCD therapeutic circuit along with determining the minimum citrate concentration required for efficacious SCD treatment.
选择性细胞滤过抑制装置 (SCD) 疗法是一种在体外回路中提供的免疫调节治疗，在严重脓毒症的临床前大型动物模型以及治疗急性肾损伤和多器官衰竭患者的临床试验中显示出前景。在 SCD 治疗期间，柠檬酸盐用于降低血液中的离子钙水平以进行抗凝和抑制白细胞活化。历史上，柠檬酸盐已被证明会干扰吸附剂透析，因此，对使用便携式透析系统的 SCD 治疗构成潜在问题。这种吸附剂透析 SCD（吸附剂 SCD）非常适合战场和自然灾害应用，在这些应用中，标准透析的供水有限，并且这些环境中的损伤类型将受益于 SCD 治疗。为了探索吸附剂和 SCD 技术的兼容性，使用 Allient 吸附剂透析系统（Renal Solutions Incorporated，Fresenius Medical Care，Warrendale，PA，USA）和同时进行的局部柠檬酸盐抗凝 SCD 治疗对尿毒症猪模型进行了测试。要评估的假设是，SCD 需要的柠檬酸盐负荷是否可以在从全身血液重新循环回治疗回路之前被代谢。尽管吸附剂 SCD 在没有任何不良血液事件的情况下保持了尿素清除率，但用于 SCD 治疗的柠檬酸盐负荷与吸附剂柱相互作用，导致透析液和全身血液中铝水平升高，潜在有毒。将需要实施吸附剂-SCD 治疗的替代策略，包括开发替代脲酶-吸附剂柱结合化学物质，或对吸附剂-SCD 治疗回路进行进一步更改，以及确定有效 SCD 治疗所需的最低柠檬酸盐浓度。
