A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.

A multicentre study of acute kidney injury in severe sepsis and septic shock: association with inflammatory phenotype and HLA genotype.
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DOI:
10.1371/journal.pone.0035838
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Busson M
Busson M
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Payen D;Lukaszewicz AC;Legrand M;Gayat E;Faivre V;Megarbane B;Azoulay E;Fieux F;Charron D;Loiseau P;Busson M

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目的探讨严重脓毒症患者急性肾损伤(AKI)的严重程度与预后、全身炎症表型及人类白细胞抗原(HLA)基因分型的关系。在两所大学医院的4个重症监护室进行的前瞻性多中心观察性研究。根据SOFA评分,至少有2个器官衰竭的严重脓毒症和感染性休克患者被分为:1)无AKI,2)轻度AKI(AKIN评分1和2分组),3)“重度AKI”(AKIN评分3期)。连续检测:血管加压药依赖指数(VDI;药物剂量和类型),以评估血流动力学状态与早期AKI的关系;血浆IL-10、巨噬细胞移动抑制因子(MIF)、IL-6和单核细胞表达。对13个人类白细胞抗原-DRB1等位基因进行基因分型,排除存在-DRB3、-DRB4和-DRB5基因。我们使用多变量分析和竞争风险模型来研究关联性。总体而言,根据AKIN评分将176名患者(有感染性休克)分为“无急性心肌梗死”(n = 43例)、“轻度急性心肌梗死”(n = 74例)或“重度急性心肌梗死”(n = 59例)。AKI组之间的VDI没有差异。校正后,“轻、重度急性肾损伤”是死亡的独立危险因素(HR 2.42 95%CI[1.01~5.83],p = 0.048;HR 1.99 95%CI[1.3 0~3.0 3],p = 0.001)。重度AKI组血浆IL-10、MIF和IL-6水平高于无AKI组和轻度AKI组(P<0.05),而MHLA-DR在第0天无差异。在接受肾脏替代治疗的患者中,人类白细胞抗原-DRB基因分型显示4个等位基因的比例(58%)显著低于未接受肾脏替代治疗的重度急性肾损伤患者(84%)(p = 0.004)。AKI严重程度与死亡率和血浆IL-10、MIF或IL-6水平独立相关。重度AKI患者存在4个等位基因可能与RRT需求较低有关。
To investigate the association between severity of acute kidney injury (AKI) and outcome, systemic inflammatory phenotype and HLA genotype in severe sepsis. Prospective multicenter observational study done in 4 intensive care units in two university hospitals. Severe sepsis and septic shock patients with at least 2 organ failures based on the SOFA score were classified: 1) "no AKI", 2) "mild AKI" (grouping stage 1 and 2 of AKIN score) and 3) "severe AKI" (stage 3 of AKIN score). Sequential measurements: The vasopressor dependency index (VDI; dose and types of drugs) to evaluate the association between hemodynamic status and the development of early AKI; plasma levels of IL-10, macrophage migration inhibitory factor (MIF), IL-6 and HLA-DR monocyte expression. Genotyping of the 13 HLA-DRB1 alleles with deduction of presence of HLA-DRB3, -DRB4 and -DRB5 genes. We used multivariate analysis with competitive risk model to study associations. Overall, 176 study patients (146 with septic shock) were classified from AKIN score as "no AKI" (n = 43), "mild AKI" (n = 74) or "severe AKI" (n = 59). The VDI did not differ between groups of AKI. After adjustment, "mild and severe AKI" were an independent risk factor for mortality (HR 2.42 95%CI[1.01-5.83], p = 0.048 and HR 1.99 95%CI[1.30-3.03], p = 0.001 respectively). "Severe AKI" had higher levels of plasma IL-10, MIF and IL-6 compared to “no AKI” and mild AKI (p<0.05 for each), with no difference in mHLA-DR at day 0. HLA-DRB genotyping showed a significantly lower proportion of 4 HLA-DRB alleles among patients requiring renal replacement therapy (RRT) (58%) than in patients with severe AKI who did not receive RRT (84%) (p = 0.004). AKI severity is independently associated with mortality and plasma IL-10, MIF or IL-6 levels. Presence of 4 alleles of HLA-DRB in severe AKI patients seems associated with a lower need of RRT.
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影响因子: 24.7
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期刊: SHOCK
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