Inflammation and subclinical infection in chronic kidney disease: A molecular approach

Inflammation and subclinical infection in chronic kidney disease: A molecular approach
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DOI:
10.1159/000096401
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发表时间:
2007-01-01
期刊:
影响因子:
3
通讯作者:
Ronco, C.
Ronco, C.
中科院分区:
医学4区
文献类型:
--
作者:
Cazzavillan, S.;Ratanarat, R.;Ronco, C.

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炎症和感染似乎是慢性肾脏病(CKD)患者发病率和死亡率的重要原因;亚临床感染已被认为是炎症综合征的重要原因,但迄今为止,这一假设仍然是推测性的。我们开发了一种用于CKD患者群体中细菌DNA存在的分子检测方法,以将分子数据与炎症的程度和水平相关联,并评估其在亚临床感染诊断中的有用性。该研究分为两个阶段:(1)筛选81名CKD患者的患病率和炎症水平以及可能的感染的存在,以及(2)38名患者的亚组,没有明显的炎症临床原因,使用细菌DNA引物进行测序,进行亚临床感染的完整分子评价。此外,在所用血液透析器的血液和透析液室中进行了全面分析。一般人群表现出一定程度的亚临床炎症,在有和无明显炎症原因的患者之间没有差异。血培养阴性的患者在使用分子方法时,细菌DNA的存在是阳性的。我们发现细菌DNA的存在与hsCRP、IL-6和氧化应激(晚期氧化蛋白产物)水平的增加以及HLA-DR平均荧光强度的降低之间存在相关趋势。血液透析器膜似乎具有粘附细菌/细菌DNA并作为浓缩器工作的特性。事实上,循环血液中细菌DNA阴性的患者在透析器的血液室中显示阳性。透析液的细菌DNA呈阴性,但所用血液透析器的透析液室呈阳性的百分比很高。此外,我们的数据表明,细菌DNA可以穿过血液透析膜。在检测亚临床感染方面,分子方法已被发现比标准方法灵敏得多。细菌DNA的存在似乎会影响炎症和免疫的某些参数的变化。除了局限性和陷阱,分子方法可能是有用的筛选亚临床感染和诊断亚临床脓毒症时,血培养是阴性的。然而,必须使用种特异性引物来鉴定所涉及的微生物。版权所有(c)2007 S. Karger AG,巴塞尔。
Inflammation and infection seem to be important causes of morbidity and mortality in chronic kidney disease ( CKD) patients; subclinical infections have been proposed as an important cause of inflammatory syndrome, but to date this hypothesis remains speculative. We developed a method for the molecular detection of the presence of bacterial DNA in a population of CKD patients in order to correlate the molecular data with the degree and level of inflammation and to evaluate its usefulness in the diagnosis of subclinical infection. The study was divided into two phases: ( 1) a population of 81 CKD patients was screened for the prevalence and level of inflammation and the presence of possible infection, and ( 2) a subgroup of 38 patients, without evident clinical causes of inflammation, underwent complete molecular evaluation for subclinical infection using bacterial DNA primers for sequencing. Additionally, complete analysis was carried out in the blood and dialysate compartments of the hemodialyzers used. The general population showed a certain degree of subclinical inflammation and no difference was found between patients with and without evident causes of inflammation. Hemoculture-negative patients were positive for the presence of bacterial DNA when molecular methods were used. We found a correlation trend between the presence of bacterial DNA and the increase in hsCRP, IL-6 and oxidative stress ( advanced oxidation protein product) levels and a reduction in the mean fluorescence intensity for HLA-DR. Hemodialyzer membranes seem to have properties that stick to bacteria/bacterial DNA and work as concentrators. In fact, patients with negative bacterial DNA in the circulating blood displayed positivity in the blood compartment of the dialyzer. The dialysate was negative for bacterial DNA but the dialysate compartment of the hemodialyzers used was positive in a high percentage. Moreover our data suggest that bacterial DNA can traverse hemodialysis membranes. Molecular methods have been found to be far more sensitive than standard methods in detecting subclinical infection. The presence of bacterial DNA seems to influence the variation in some parameters of inflammation and immunity. Apart from the limitations and pitfalls, the molecular method could be useful to screen for subclinical infection and diagnose subclinical sepsis when the hemoculture is negative. However, the identification of the microorganism implicated must be done with species-specific primers. Copyright (c) 2007 S. Karger AG, Basel.