Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis.
Anakinra Removal by Continuous Renal Replacement Therapy: An Ex Vivo Analysis.
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DOI：
10.1097/cce.0000000000001010
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发表时间：
2023-12
影响因子：
--
通讯作者：
Edginton AN
中科院分区：
文献类型：
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作者：
Dubinsky SDJ;Watt KM;Imburgia CE;Mcknite AM;Hunt JP;Rice C;Rower JE;Edginton AN
脓毒症患者存在多器官功能障碍的显著风险，包括肺和肾。为了控制与肾损害相关的发病率，可能需要连续性肾脏替代治疗（CRRT）。CRRT中阿那白滞素的药代动力学程度仍未知。本研究的目的是研究阿那白滞素-回路相互作用，并量化从血浆中清除的速率。使用闭环离体CRRT回路评价阿那白滞素-回路相互作用。基于溶质清除方法分三个阶段进行CRRT：1）血液滤过，2）血液透析，3）血液透析滤过。包括阿那白滞素的标准对照样品以评估药物降解。大学研究实验室。没有。将阿那白滞素给予CRRT回路，并沿着收集系列过滤器前血液样本以及时间匹配的对照和血液滤液样本。每个回路重复运行三次，以评估运行间变异性。通过酶联免疫吸附测定法测定每种参考液中阿那白滞素的浓度。通过筛分系数/透析液饱和常数和回路流速的乘积估计跨膜过滤器清除率。对于每种CRRT模式，阿那白滞素从血浆中的清除在几分钟内发生。阿那白滞素给药后血浆中平均药物残留（%）在血液透析滤过组最低（34.9%）。血液透析滤过、血液滤过和血液透析的平均筛选系数分别为0.34、0.37和0.41。各模式的跨膜清除率相当一致，血液透析期间最高（5.53 mL/min），其次是血液透析滤过（4.99 mL/min）和血液滤过（3.94 mL/min）。对照样品中残留的药物百分比（93.1%）在各实验中保持一致，表明血液中的降解可忽略不计。该分析的结果首次证明了采用现代CRRT技术可从血浆中清除大分子治疗性蛋白质（如阿那白滞素）。重度肾损害患者的当前给药建议可能导致接受CRRT的患者阿那白滞素浓度低于治疗水平。
Patients with sepsis are at significant risk for multiple organ dysfunction, including the lungs and kidneys. To manage the morbidity associated with kidney impairment, continuous renal replacement therapy (CRRT) may be required. The extent of anakinra pharmacokinetics in CRRT remains unknown. The objectives of this study were to investigate the anakinra–circuit interaction and quantify the rate of removal from plasma. The anakinra–circuit interaction was evaluated using a closed-loop ex vivo CRRT circuit. CRRT was performed in three phases based on the method of solute removal: 1) hemofiltration, 2) hemodialysis, and 3) hemodiafiltration. Standard control samples of anakinra were included to assess drug degradation. University research laboratory. None. Anakinra was administered to the CRRT circuit and serial prefilter blood samples were collected along with time-matched control and hemofiltrate samples. Each circuit was run in triplicate to assess inter-run variability. Concentrations of anakinra in each reference fluid were measured by enzyme-linked immunosorbent assay. Transmembrane filter clearance was estimated by the product of the sieving coefficient/dialysate saturation constant and circuit flow rates. Removal of anakinra from plasma occurred within minutes for each CRRT modality. Average drug remaining (%) in plasma following anakinra administration was lowest with hemodiafiltration (34.9%). The average sieving coefficient was 0.34, 0.37, and 0.41 for hemodiafiltration, hemofiltration, and hemodialysis, respectively. Transmembrane clearance was fairly consistent across each modality with the highest during hemodialysis (5.53 mL/min), followed by hemodiafiltration (4.99 mL/min), and hemofiltration (3.94 mL/min). Percent drug remaining within the control samples (93.1%) remained consistent across each experiment, indicating negligible degradation within the blood. The results of this analysis are the first to demonstrate that large molecule therapeutic proteins such as anakinra, are removed from plasma with modern CRRT technology. Current dosing recommendations for patients with severe renal impairment may result in subtherapeutic anakinra concentrations in those receiving CRRT.