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院内急性肾损伤患者的预后相关研究
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摘要
第一部分院内急性肾损伤患者的临床特点和预后因素
     目的
     分析院内急性肾损伤(acute kidney injury, AKI)患者的临床特点,并探讨AKI患者90天死亡的预后因素。
     研究对象和方法
     本研究为前瞻性队列研究,共纳入357例院内AKI的患者,根据RIFLE(风险,损伤,衰竭,丢失或终末期肾病)标准对患者进行危险分级,收集临床资料及实验室检查结果,分析90天全因死亡率的预后因素。
     结果
     在357例住院AKI患者中,患者年龄越高,占总人数的比例越大;且90天死亡的患者为159例,死亡率达44.5%。单因素分析显示,死亡组和存活组在机械通气、脓毒症以及多项实验室指标等方面有统计学差异(p<0.05)。多因素Cox回归模型提示,与AKI患者90天预后相关的危险因素包括PLT、TB、前白蛋白、GCS、MAP、BUN (p<0.05),且回归方程Y的受试者工作特征曲线(receiver operator characteristic curve, ROC)曲线下面积=0.847,有一定预测价值。
     结论
     AKI是急危重症,病死率高。多因素Cox回归模型提示,与AKI患者90天预后相关的独立危险因素包括PLT、TB、前白蛋白、GCS、MAP、BUN,且回归方程Y预测预后有一定价值。合理使用这些指标,有助于临床医师判断住院AKI患者的预后,及早干预进而改善预后。
     第二部分血清炎症指标和营养指标与住院AKI患者预后的关系研究
     目的
     比较AKI患者和血透患者、腹透患者及健康对照组体内的炎症指标和营养指标水平,探讨血清炎症指标和营养指标的组合与AKI患者90天死亡的关系。
     研究对象与方法
     本研究为前瞻性队列研究,根据RIFLE标准,共纳入155例院内获得性AKI患者。在确诊AKI时,检测患者的炎症指标C-反应蛋白(CRP),营养指标(白蛋白,前白蛋白和胆固醇)水平,随访90天全因死亡率。此外,也检测健康对照组、维持性血液透析和腹膜透析患者的血清CRP和营养指标水平,与AKI患者进行比较。各组人群在年龄、性别方面相匹配。
     结果
     AKI患者与健康对照组、维持性血液透析或腹膜透析的终末期肾脏疾病患者相比, CRP/前白蛋白水平显著升高(p<0.001)。将AKI患者分为死亡组和存活组,死亡组血清CRP显著升高,而白蛋白,前白蛋白和胆固醇水平显著降低(p<0.001);同样,指标组合如CRP/白蛋白、CRP/前白蛋白和CRP/胆固醇比值在死亡组也明显高于存活组(p<0.001)。多元统计分析(Cox回归)显示,经年龄、性别、脓毒症和SOFA校正后,CRP/前白蛋白是AKI患者独立的死亡预测因子(p=0.027),而其他指标(CRP、白蛋白、前白蛋白、胆固醇、CRP/白蛋白和CRP/胆固醇)则无统计学意义。根据CRP/前白蛋白水平的四分位数分为4组,随四分位数的增高,患者死亡的风险比分别为1.00(参考基准)、1.85、2.25和3.89(p=0.01),也随之升高。
     结论
     AKI患者常伴有炎症和营养不良。CRP/前白蛋白水平可预测AKI患者90天死亡,且独立于病情严重程度。除了SOFA评分,它可能在评估病情的严重程度和预测AKI患者的预后方面有一定价值。
     第三部分血浆3-硝基酪氨酸和巯基与住院AKI患者预后的关系研究
     目的
     分析急性肾损伤(AKI)患者的氧化应激的特点,比较AKI患者、非AKI的危重患者及健康对照组体内的血浆蛋白氧化标志物的水平,并探讨血浆蛋白氧化水平和AKI患者90天死亡率之间的关联。
     研究对象和方法
     本研究为前瞻性队列研究,共纳入158例院内AKI的患者,根据RIFLE(风险,损伤,衰竭,丢失或终末期肾病)标准对患者进行危险分级。对照组包括12例非AKI的危重患者和15例健康受试者,2组对照在年龄和性别方面与AKI组相匹配。检测各组人群体内的血浆蛋白氧化标记物水平,分析全因死亡率与AKI患者血浆蛋白氧化的生物标志物(3-硝基酪氨酸和巯基)之间的关系。
     结果
     AKI患者的血浆3-NT/Tyr在AKI组为(395.9±369.8),显著高于健康对照(8.1±10.7)和非AKI的危重病人(45.9±68.4)(ANOVA,p<0.001)。AKI患者血浆巯基浓度(290.1±99.1umol/L)比健康对照组低(408.0±79.6umol/L),但高于非AKI的危重病人(196.1±94.9umol/L)(ANOVA,p=0.002)。3-NT/Tyr水平与AKI的严重程度(ANOVA,p<0.001)显著相关。高3-NT/Tyr或高巯基浓度的患者90天的全因死亡率显着高于低水平组(log-rank检验分别为:p=0.001;p=0.032)。多元统计分析(Cox回归)显示,经年龄、性别、脓毒症和APACHE II评分校正后,3-NT/Tyr和巯基水平仍与90天死亡率显著相关(检验结果分别为:p=0.025,p=0.008)。
     结论
     AKI患者的血浆中存在过度的蛋白质氧化,表现为硝基酪氨酸含量的增加和巯基含量的减少。3-NT和巯基与AKI的患者90天死亡率显著相关,且独立于病情严重程度。
PART1Clinical Characteristics and Prognostic Factors in Patients with Hospital-acquired Acute Kidney Injury
     Objectives
     To examine clinical characteristics and prognostic factors in patients with hospital-acquired acute kidney injury and to investigate the risk factors for90days all-cause mortality.
     Patients and Methods
     357patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE criteria. Clinical data and laboratory test results were collected and the etiology and distribution characteristics of patients with AKI were analyzed. Cox regression analysis was used to investigate the prognostic risk factors of AKI.
     Results
     159patients died within90days, and the mortality reached44.5%. Univariate analysis showed that death group and survival group were significantly different in mechanical ventilation, sepsis, and several laboratory indicators (p<0.05). Cox regression model suggested that PLT、TB、prealbumin、GCS、MAP and BUN were independent prognostic risk factors for patients with AKI (p<0.05), and the area under the ROC curve was0.847, indicating potential predictive value for90days mortality.
     Conclusions
     AKI is one of the most common clinical syndromes in hospitalized patients.PLT、 TB、prealbumin、GCS、MAP、BUN are independent prognostic risk factors of patients with hospital-acquired AKI.
     PART2The Ratio of CRP to Prealbumin Levels Predict Mortality in Patients with Hospital-acquired Acute Kidney Injury
     Objectives
     To examine whether the combination of inflammatory and nutritional markers could predict the mortality of AKI patients.
     Patients and Methods
     155patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE criteria. C-reactive protein (CRP), and the nutritional markers (albumin, prealbumin and cholesterol) measured at nephrology consultation were analyzed in relation to all cause mortality of these patients. In addition, CRP and prealbumin were also measured in healthy controls, maintenance hemodialysis and peritoneal dialysis patients and then compared with AKI patients.
     Results
     Compared with healthy controls and end-stage renal disease patients on maintenance hemodialysis or peritoneal dialysis, patients with AKI had significantly higher levels of CRP/prealbumin (p<0.001). Higher level of serum CRP and lower levels of albumin, prealbumin and cholesterol were found to be significant in the patients with AKI who died than those who survived. Similarly, the combined factors including the ratio of CRP to albumin (CRP/albumin)、CRP/prealbumin and CRP/cholesterol were also significantly higher in the former group (p<0.001for all). Multivariate analysis (Cox regression) revealed that CRP/prealbumin was independently associated with mortality after adjustment for age, gender, sepsis and SOFA (p=0.027) while the others (CRP, albumin, prealbumin, cholesterol, CRP/albumin and CRP/cholesterol) became non-significantly associated. The hazard ratio was1.00(reference),1.85,2.25and3.89for CRP/prealbumin increasing according to quartiles (p=0.01).
     Conclusions
     Inflammation and malnutrition were common in patients with AKI. Higher level of the ratio of CRP to prealbumin was associated with mortality of AKI patients independent of the severity of illness and it may be a valuable addition to SOFA score to predict the prognosis of AKI patients.
     PART3Nitrotyrosine and Thiol Levels were Associated with Mortality in Patients with Acute Kidney Injury
     Objectives
     To examine the characteristics of oxidative stress in patients with acute kidney injury (AKI) and investigate the association between plasma protein oxidation levels and90-day mortality in patients with AKI.
     Patients and Methods
     158patients with hospital-acquired AKI were recruited to this prospective cohort study according to RIFLE (Risk, Injury, Failure, Lost or End Stage Kidney) criteria. Twelve critically ill patients without AKI and15age and gender-matched healthy subjects were enrolled as control. Plasma protein oxidation biomarkers (3-nitrotyrosine and thiol) were analyzed in relation to all cause mortality of patients with AKI.
     Results
     Highest3-NT/Tyr was detected in patients with AKI compared with healthy subjects, and critically ill patients without AKI (ANOVA p<0.001). The concentration of thiol group in AKI patients was lower than that of healthy people but higher than that of critically ill patient (ANOVA, p=0.002). The3-NT/Tyr level was significantly associated with the severity of AKI (ANOVA, p<0.001). The90-day overall mortality was significantly higher in the group with high3-NT/Tyr (p=0.001by log-rank test) or high thiol concentration (p=0.032by log-rank test). Multivariate analysis (Cox regression) revealed that3-NT/Tyr (p=0.025) and thiol (p=0.008) were independently associated with mortality after adjustment for age、gender、sepsis and Acute Physiology and Chronic Health Evaluation (APACHE) Ⅱ score.
     Conclusions
     There is excess plasma protein oxidation in patients with AKI, as evidenced by increased nitrotyrosine content and diminished thiol content.3-NT and thiol were associated with mortality of AKI patients independent of the severity of illness.
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