Case Report: Atypical HUS Presenting With Acute Rhabdomyolysis Highlights the Need for Individualized Eculizumab Dosing.
Case Report: Atypical HUS Presenting With Acute Rhabdomyolysis Highlights the Need for Individualized Eculizumab Dosing.
复制标题
DOI：
10.3389/fped.2022.841051
复制
发表时间：
2022
影响因子：
2.6
通讯作者：
Drake KA
中科院分区：
文献类型：
--
作者：
Benoit SW;Fukuda T;VandenHeuvel K;Witte D;Fuller C;Willis J;Dixon BP;Drake KA
非典型溶血性尿毒症综合征（aHUS）是一种罕见的孤儿病，由补体激活失调导致血栓性微血管病变。虽然补体介导的内皮损伤主要影响肾脏微血管，但在相当比例的患者中存在肾外表现。虽然eculizumab显著改善了这种罕见疾病的发病率和死亡率，但优化这种昂贵药物的治疗方案仍然是治疗aHUS的一个活跃研究领域。本报告描述了一个先前健康的4岁男性病例，他在aHUS发展之前出现横纹肌溶解，无尿肾损伤需要透析。与基于体重的标准化指南相比，临床稳定需要增加和更频繁的eculizumab剂量。在他的疾病维持阶段，药代动力学分析表明，每3周个体化给药方案可以维持足够的eculizumab水平，而不是标准的2周给药，这在该患者4年的随访期间得到了证实。成本分析表明，基于体重的维持剂量每年花费312,000美元，而将剂量间隔延长至每3周一次将花费208,000美元，每年节省104,000美元，而在最初住院期间更频繁地使用eculizumab以抑制其急性疾病所需的费用为72,000美元。该病例体现了严重的、多系统累及aHUS的可能性，表现为肾外表现，包括横纹肌溶解，并强调了在患者疾病过程中个体化给药eculizumab改善临床结果和更高价值护理的可能性。
Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare orphan disease caused by dysregulated complement activation resulting in thrombotic microangiopathy. Although complement-mediated endothelial injury predominantly affects the renal microvasculature, extra-renal manifestations are present in a significant proportion of patients. While eculizumab has significantly improved the morbidity and mortality of this rare disease, optimizing therapeutic regimens of this highly expensive drug remains an active area of research in the treatment of aHUS. This report describes the case of a previously healthy 4 year-old male who presented with rhabdomyolysis preceding the development of aHUS with anuric kidney injury requiring dialysis. Clinical stabilization required increased and more frequent eculizumab doses compared with the standardized weight-based guidelines. In the maintenance phase of his disease, pharmacokinetic analysis indicated adequate eculizumab levels could be maintained with an individualized dosing regimen every 3 weeks, as opposed to standard 2 week dosing, confirmed in this patient over a 4 year follow up period. Cost analyses show that weight-based maintenance dosing costs $312,000 per year, while extending the dosing interval to every 3 weeks would cost $208,000, a savings of $104,000 per year, relative to the cost of $72,000 from more frequent eculizumab dosing during his initial hospitalization to suppress his acute disease. This case exemplifies the potential of severe, multisystem involvement of aHUS presenting with extra-renal manifestations, including rhabdomyolysis as in this case, and highlights the possibility for improved clinical outcomes and higher value care with individualized eculizumab dosing in patients over the course of their disease.
登录
查看更多内容
影响因子：
20.3
作者：
Jodele, Sonata;Dandoy, Christopher E.;Davies, Stella M.
通讯作者：
Davies, Stella M.
影响因子：
13.2
作者：
Ardissino, Gianluigi;Testa, Sara;Cugno, Massimo
通讯作者：
Cugno, Massimo
影响因子：
7.3
作者：
Bouwmeester RN;Ter Avest M;Wijnsma KL;Duineveld C;Ter Heine R;Volokhina EB;Van Den Heuvel LPWJ;Wetzels JFM;van de Kar NCAJ
通讯作者：
van de Kar NCAJ
DOI：
10.1016/j.nefro.2015.07.005
发表时间：
2015-01-01
期刊：
Nefrología (Madrid)
影响因子：
--
作者：
Campistol, Josep M.;Arias, Manuel;Rodríguez de Córdoba, Santiago
通讯作者：
Rodríguez de Córdoba, Santiago
影响因子：
2.2
作者：
Willrich, Maria A., V;Ladwig, Paula M.;Murray, David L.
通讯作者：
Murray, David L.