Balanced Hydroxyethylstarch (HES 130/0.4) Impairs Kidney Function In-Vivo without Inflammation.
Balanced Hydroxyethylstarch (HES 130/0.4) Impairs Kidney Function In-Vivo without Inflammation.
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DOI：
10.1371/journal.pone.0137247
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wunder C
中科院分区：
文献类型：
--
作者：
Schick MA;Baar W;Bruno RR;Wollborn J;Held C;Schneider R;Flemming S;Schlegel N;Roewer N;Neuhaus W;Wunder C
容量治疗是日常围手术期护理的标准程序，目前正在讨论羟乙基淀粉（HES）胶体复苏的益处。在脓毒症中，由于发生急性肾损伤（阿基）的风险较高，应避免使用HES。在无脓毒症患者中使用羟乙基淀粉的结果存在争议。因此，我们进行了一项动物研究，以评价6% HES 130/0.4对脓毒症或健康条件下肾脏完整性的影响。脓毒症由标准化结肠升结肠支架腹膜炎（sCASP）诱导。sCASP-组和对照组（C）保持不处理24 h。18 h后sCASP+HES组（sCASP+VOL）和对照组+HES组（C+VOL）分别给予50 ml/KG平衡的6%HES（VOL）130/0.4，持续6 h。24小时后，在再次麻醉的大鼠中通过菊糖和PAH清除率测量肾功能，并分析血清尿素、肌酐（crea）、胱抑素C和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）以及组织病理学。体外培养人近曲小管上皮细胞（PTC），加入0.1- 4.0%Vol的脂多糖（LPS），用XTT-法测定细胞活力，LDH-法测定细胞毒性。sCASP诱导的重度脓毒症阿基显示了通过清除率或肌酐测量（侧重于VOL）获得的肾功能不同结果。Soleley HES（C+VOL）在无sCASP的情况下肾功能恶化。组织学检查显示，与对照组相比，所有HES组均出现显著紊乱。在体外LPS并没有恶化的羟乙基淀粉诱导的PTC细胞的细胞活力降低。我们首次证明，在体内应用50 ml/KG 6% HES 130/0.4 6小时可诱导阿基，而无炎症。sCASP诱导的脓毒性阿基的严重程度可能不再对扩容方式敏感。
Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES). In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI). Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP). sCASP-group as well as control group (C) remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL) and control+HES (C+VOL) received 50 ml/KG balanced 6% HES (VOL) 130/0.4 over 6h. After 24h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea), cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as well as histopathology were analysed. In vitro human proximal tubule cells (PTC) were cultured +/- lipopolysaccharid (LPS) and with 0.1–4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL) deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion.