不同急性肾损伤分期的MODS患者连续肾脏替代治疗预后分析

目的探讨RIFLE标准的急性肾损伤(AKI)分期与连续性肾脏替代治疗(CRRT)的多器官功能障碍综合征(MODS)患者预后的关系。方法回顾性分析第四军医大学西京医院肾脏病科2004年以来行连续性静脉-静脉血液滤过(CVVH)治疗的240例MODS患者,按RIFLE标准分为AKIⅠ期、Ⅱ期和Ⅲ期,对比分析不同AKI分期患者的医院死亡率和器官衰竭数,并将CVVH治疗前和治疗24h后的APACHEII评分、SOFA评分、平均动脉压(MAP)、氧合指数、血尿素氮(BUN)和血肌酐(Scr)等指标进行比较。结果①全部患者死亡率为38.75%,AKIⅢ期患者医院死亡率高于AKIⅠ期和Ⅱ期患者(P<0.05)。②随着AKI分期的加重,患者器官衰竭数增加(P=0.001)。发生脏器衰竭≥4个的患者医院死亡率明显高于脏器衰竭数≤3个的患者,(75.5%vs13.4%,P<0.05)。③CVVH治疗24h后,患者MAP、氧合指数、BUN和Scr均明显改善;APACHE II评分和SOFA评分在AKII期和II期患者显著降低,在AKI III期患者中则变化无显著性。结论CVVH是防治MODS合并重症ARF患者的有效手段,RILFE标准对AKI早期诊断和判断预后有指导意义。必须强调CVVH时机的选择,早期(AKIⅠ期和Ⅱ期)行CVVH可以明显改善MODS患者的预后。     

传统肾脏替代治疗开始指标在判断重症急性肾损伤患者预后的价值

目的 探讨血清肌酐(serum creatinine,SCr)或尿素氮(blood urea nitrogen,BUN)水平、急性肾损伤(acute kidney injury,AKI)分级等传统肾脏替代治疗(renal replacement therapy,RRT)开始指标在判断重症AKI患者预后的价值.方法 采用回顾性分析方法,选择在2011年1月至2015年1月期间入住浙江省人民医院重症监护病房诊断为AKI并接受连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)治疗的258例成年患者,根据出院时预后分为存活组(n=104)和死亡组(n=154),比较两组患者在一般情况、疾病组成,CRRT治疗前肾功能情况(尿量、SCr、BUN和AKI分级)、内环境稳态(酸碱平衡和电解质水平)和疾病严重程度(APACHEⅡ评分和SOFA评分)等指标上的差异.同时采用多因素Cox比例风险模型和ROC曲线分析,筛选影响重症AKI患者预后的危险因素.结果 两组患者在性别、年龄、原发疾病性质、AKI病因组成、CRRT治疗前APACHEⅡ评分、肾功能情况(AKI分级、尿量、BUN和SCr)、血钾和血磷水平等因素上差异无统计学意义(均P ＞0.05);但死亡组中严重脓毒症患者比例更高(31.17％ vs.19.23％,P=0.033)、pH值更低(7.27±0.34 vs.7.41 ±0.34,P=0.024)、乳酸水平更高(3.97±2.87vs.2.64±2.30,P=0.006);采用多因素Cox比例风险模型检验分析后发现,仅血磷水平(P =0.043)和乳酸水平(P =0.009)为影响重症AKI患者预后的独立危险因素,而SCr、BUN、AKI分级、尿量、pH值、碳酸氢根水平(HC03-)、血钾水平等传统RRT开始参考指标则与患者预后无显著相关(均P＞0.05).因此,将pH值、HC03-、血钾水平、血磷水平、尿量和AKI分级这六项传统指标进行综合,采用受试者工作特征(ROC)曲线分析并比较综合指标和SCr、BUN、乳酸等因素在预测重症AKI患者院内病死率的作用,结果显示综合指标和乳酸的曲线下面积(AUC)较高,分别为0.669(95％ CI:0.577～0.762)和0.683(95％CI:0.590 ～0.777),而SCr和BUN这两项指标的AUC均＜0.5,分别为0.460(95％ CI:0.358 ～0.562)和0.469 (95％ CI:0.366～0.571).结论 在预测重症AKI患者预后的作用上,RRT治疗前的综合指标优于任一传统RRT开始参考指标.因此,临床上在判断重症AKI患者何时应开始RRT治疗时,应综合考虑,而不是根据某一指标.     

危重病评分及急性肾损伤分期在行连续性肾脏替代治疗的急性肾损伤患者预后中的应用价值

目的 探讨急性生理学与慢性健康状况评分(acute physiology and chronic health evaluation,APACHE)Ⅱ、多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)评分、序贯性脏器衰竭评分(sequential organ failure assessment,SOFA)3种危重病评分系统和急性肾损伤(acute kidney injury,AKI)分期在行连续性肾脏替代治疗(continuous renal replacement therapy,CRRT)的AKI患者中对预后的判断价值.方法 以2006年1月至2010年12月上海交通大学附属第六人民医院重症监护病房(intensive care unit,ICU)及急诊重症监护病房(emergency intensire care unit,EICU)行CRRT治疗的AKI患者为研究对象,在入ICU、开始CRRT时分别进行APACHE Ⅱ、MODS、SOFA评分和AKl分期,并用受试者工作特征(receiver operating characteristiC,ROC)曲线进行预后分析.结果 共收集患者117例,117例患者存活45例,死亡72例,总病死率为61.5%.剔除肾脏替代治疗作为AKI分期标准,有25例AKI 3期的患者在CRRT时分别纳入AKI 1期和2期.APACHE ⅡCRRT、MODSCRRT、SOFACRRT的ROC曲线下面积分别为0.901、0.851、0.885(P＜0.001),而AKICRRT的ROC曲线下面积为0.617(P=0.034).结论 APACHE Ⅱ、MODS及SOFA评分系统对行CRRT的AKI患者预后的判断价值较高,而AKI分期则意义不大.     

可溶性CD73联合SOFA评分对脓毒症相关急性肾损伤患者28 d死亡风险的预测价值

目的探讨血清可溶性CD73(sCD73)联合序贯器官衰竭评分(SOFA)对脓毒症相关急性肾损伤(SA-AKI)患者28d死亡风险的预测价值。方法前瞻性收集184例SA-AKI患者和50例健康志愿者临床资料。根据28 d转归将SA-AKI患者分为存活组(n=142)和死亡组(n=42)。按AKI分期标准分为AKIⅠ期(n=90)、AKIⅡ期(n=50)和AKIⅢ期(n=44)。单因素和多因素Logistic回归分析临床资料,确定SA-AKI患者28 d死亡的独立影响因素。Spearman相关性分析探讨SA-AKI患者血清sCD73水平与SOFA评分的相关性。利用受试者工作特征(ROC)曲线评估血清sCD73水平、SOFA评分及两者联合检测对SA-AKI患者28 d死亡风险的预测价值。结果SA-AKI患者血清sCD73水平明显高于健康志愿者[μg/L:7.42(4.29,11.23)vs.5.37(3.14,7.27),P<0.001]。SA-AKI患者28 d病死率为22.8%(42/184)。死亡组血清sCD73水平明显低于存活组[μg/L:2.76(1.78,7.32)vs.8.07(5.81,11.75),P<0.001],SOFA评分明显高于存活组(分:10.67±3.03 vs.7.53±2.89,P<0.001)。随AKI分期的增加,SA-AKI患者血清sCD73水平依次降低,SOFA评分依次升高,差异均有统计学意义(P<0.05)。多因素Logistic回归分析显示,年龄(OR=1.088,95%CI 1.039~1.139,P<0.001)、SOFA评分(OR=1.341,95%CI 1.127~1.597,P=0.001)、AKIⅡ期(OR=8.719,95%CI 1.665~45.651,P=0.010)、AKIⅢ期(OR=29.920,95%CI 5.009~178.709,P<0.001)、连续性肾脏替代治疗(OR=0.138,95%CI 0.027~0.693,P=0.016)和sCD73(OR=0.910,95%CI 0.833~0.993,P=0.034)是SA-AKI患者28 d死亡的独立影响因素。血清sCD73水平与SOFA评分呈负相关(rs=-0.319,P<0.001)。ROC曲线分析结果显示,血清sCD73水平与SOFA评分联合检测预测SA-AKI患者28 d死亡风险的AUC明显高于两个指标单独预测(0.854 vs.0.766,Z=2.160,P<0.05;0.854 vs.0.785,Z=2.925,P<0.05)。血清sCD73最佳截断值为5.84μg/L时,诊断敏感度为71.43%,特异度为72.54%;SOFA评分最佳截断值为8分时,诊断敏感度为80.96%,特异度为66.90%。两者联合检测的敏感度为83.33%,特异度为78.87%。结论血清sCD73水平降低、SOFA评分升高是SA-AKI患者28 d死亡的独立危险因素,两者联合检测对SA-AKI患者的28 d死亡风险具有良好的预测价值。     

KDIGO标准APACHEⅡ与SOFA评分对脓毒症急性肾损伤患者的预后评估

目的 探讨急性肾损伤国际指南(KDIGO)制定的急性肾损伤(AKI)诊断分期标准、急性生理与慢性健康状况评分Ⅱ(APACHEⅡ)和序贯器官衰竭评估(SOFA)评分对脓毒症AKI患者的预后评估价值.方法 前瞻收集2012-03-01 ～2013-03-01期间在我院ICU接受治疗的脓毒症患者的临床资料,采用KDIGO标准对脓毒症患者进行AKI诊断和分期；根据患者入ICU第1个24h内的生理指标最差值进行APACHEⅡ和SOFA评分,并用受试者工作特征(ROC)曲线评估3项系统对预后评估的准确性.以Logistic多元回归分析对预后的影响.结果 共280例脓毒症患者,占同期ICU住院患者的41.7％ (280/670),总体院内死亡率为29.8％.脓毒症肾损伤168例,占脓毒症患者的60％,其中1期76例,死亡率22.4％；2期48例,死亡率37.5％；3期44例,死亡率72.7％.脓毒症肾损伤患者的APACHEⅡ及SOFA评分均高于非AKI患者(P＜0.05).Logistic多元回归分析显示,APACHEⅡ评分＞22分(OR =4.50),KDIGO分期1、2、3期(OR值分别为2.31、7.44、45.00)是脓毒症并AKI患者院内死亡的独立预测指标.结论 KDIGO诊断标准与APACHEⅡ、SOFA评分对脓毒症肾损伤患者整体预后都有较好的预测价值.     

连续肾脏替代疗法治疗急性肾损伤的老年重症患者90d死亡的相关影响因素分析

目的明确连续肾脏替代疗法(CRRT)治疗急性肾损伤(AKI)的老年重症患者90 d死亡的影响因素。方法以2013年12月至2015年3月于我院重症医学科住院的接受CRRT的AKI老年重症患者82例为研究对象,收集所有患者各项临床指标包括年龄、性别、体重、入院时基础血清肌酐浓度、入ICU时血清白蛋白浓度、CRRT开始前APACHEⅡ评分、SOFA评分、应用机械通气及血管活性药物的情况和血清肌酐浓度、入ICU至开始CRRT间隔时间、KDIGO分期,计算入住ICU后5 d内出入量液体平衡和5 d内总液体蓄积量(L)占体重(kg)百分比(即液体蓄积),根据患者90 d存活情况,分为生存组和死亡组,分析接受CRRT的AKI老年重症患者90 d死亡的相关危险因素。结果接受CRRT的AKI老年重症患者90 d内死亡率51.2%,40例生存者中依赖肾脏替代治疗的占25%。单因素分析显示:与生存组比较,死亡组年龄更大,体重更轻,入ICU时血清白蛋白浓度更低,APACHEⅡ评分和SOFA评分更高,液体蓄积更多,合并严重感染、使用血管活性药物比例更大(P<0.05)。多元Logistic回归分析显示液体蓄积多(OR=1.032,95%CI 1.012~1.083)、高龄(OR=1.021,95%CI 1.005~1.075)、SOFA评分高(OR=1.218,95%CI 1.074~1.580)、使用血管活性药物(OR=1.016,95%CI 1.007~1.273)和白蛋白浓度低(OR=0.816,95%CI 0.751~0.967)是影响接受CRRT的AKI老年重症患者90 d死亡的危险因素。结论体内液体蓄积多、SOFA评分高、年龄大、使用血管活性药物和低白蛋白浓度是接受CRRT的AKI老年重症患者90 d死亡的影响因素。     

危重病评分系统预测急性肾损伤患者预后优于RIFLE分级

目的评价并比较序贯性脏器衰竭评分(sequential organ failure assessment,SOFA)、急性生理学与慢性健康状况评分(acute physiology and chronic health evaluation,APACHE)Ⅱ、简明急性生理学评分(simplified acute physiology score,SAPS)Ⅱ和Liano评分4种危重病评分系统及RIFLE标准对急性肾损伤(acute kidney injury,AKI)患者的预后评估价值。方法本研究为前瞻性、单中心研究,收集2008年12月到2009年11月复旦大学附属华山医院各种病因引起的AKI患者。AKI的诊断标准为RIFLE的肌酐标准,除外肾后性、肾小球性、肾血管性和间质性肾炎等引起的急性损伤。研究的主要终点是28d死亡率。比较存活组和死亡组的RIFLE分级、SOFA、APACHEⅡ、SAPSⅡ和Liano评分,并进行各种评分系统对死亡的ROC曲线分析,同时将4种评分方法根据RIFLE分级进行分层分析。结果共入选194例符合入选标准的AKI患者。存活组和死亡组的RIFLE分级、AKI病因、是否需要透析差异无统计学意义(P0.05)。死亡组的机械通气比例、SOFA、APACHEⅡ、SAPSⅡ和Liano评分显著高于存活组(P0.001)。SOFA、APACHEⅡ、SAPSⅡ和Liano评分预测死亡的受试者工作特性(ROC)曲线下面积分别为0.900、0.885、0.888、0.875(均P0.001),而RIFLE的ROC曲线下面积为0.566(P0.05)。按AKI的RIFLE级别进行分层分析时发现,4个评分方法在衰竭组(Fc)ROC曲线下面积最大,其中又以Liano评分最高。结论 RIFLE分级对AKI患者的预后无明显的判断价值,而危重病评分包括SOFA、APACHEⅡ、SAPSⅡ和Liano评分对AKI的预后具有良好的预测价值。     

去甲肾上腺素联合艾司洛尔对脓毒症休克患者心肌功能及乳酸清除率的影响

目的探讨去甲肾上腺素联合艾司洛尔对脓毒症休克患者心肌功能和乳酸清除率的影响。方法 100例脓毒症休克患者依据入院顺序分为对照组(n=48)与观察组(n=52)。所有患者均给予规范抗感染和液体复苏治疗,对照组在此基础上采用去甲肾上腺素治疗,观察组在对照组基础上联合艾司洛尔治疗。比较2组机械通气时间、重症加强护理病房(ICU)住院时间、6 h内复苏成功率以及治疗前后心肌功能、血乳酸浓度和乳酸清除率、组织灌注情况、序贯器官衰竭估计(SOFA)评分、急性生理与慢性健康(APACHE-Ⅱ)评分。结果观察组机械通气时间、ICU住院时间显著短于对照组,6 h内复苏成功率和治疗7 d后乳酸清除率显著高于对照组(P 0. 05)。治疗前,2组B型尿钠肽(BNP)、肌钙蛋白T(cTnT)及磷酸肌酸同工酶(CK-MB)、尿量、中心静脉血氧饱和度(ScvO_2)、SOFA评分、APACHEⅡ评分比较无显著差异(P 0. 05);治疗后,2组BNP、cTnT及CK-MB、SOFA评分、APACHEⅡ评分均较治疗前显著下降(P 0. 05),观察组上述指标显著低于对照组(P 0. 05),尿量、ScvO_2均较治疗前显著上升(P 0. 05),观察组尿量、ScvO_2显著高于对照组(P 0. 05)。结论去甲肾上腺素联合艾司洛尔能够提高脓毒症休克的疗效,保护心肌功能,提高乳酸清除率,减轻患者组织缺氧程度。     

血浆可溶性白细胞分化抗原14早期预测脓毒症患者发生急性肾损伤的价值

目的 观察脓毒症患者血浆可溶性白细胞分化抗原14(soluble leukocyte differentiation antigen 14, sCD14)水平变化,探讨其对脓毒症患者发生急性肾损伤(acute kidney injury, AKI)的早期预测价值。方法 脓毒症患者80例,发生AKI者58例为AKI组,未发生AKI者22例为非AKI组。比较2组入住ICU 24 h内急性生理学和慢性健康状况评价Ⅱ(acute physiology and chronic health scoring systemⅡ,脓毒症休克比率55.17%,APACHEⅡ)评分、序贯器官衰竭(sequential organ failure assessment, SOFA)评分及入住ICU次日血浆sCD14、血清降钙素原、乳酸、肌酐、白细胞介素-6、C反应蛋白水平,估算肾小球滤过率,入住ICU 24 h尿量;绘制ROC曲线,评估血浆sCD14对脓毒症患者发生AKI的预测价值。结果 AKI组血浆sCD14[705.37(428.11,925.96) ng/L],血清肌酐[120.88(101.07,13...     

阿托伐他汀治疗对急性心力衰竭患者炎症标志物和急性肾损伤的影响

目的探讨阿托伐他汀治疗对急性心力衰竭(AHF)患者炎症标志物和急性肾损伤(AKI)的影响。方法选择2012年10月至2014年7月在惠州市仲恺高新区人民医院收治并诊断为AHF的患者92例,将其随机分为阿托伐他汀治疗组(46例)和对照组(46例)。治疗组入院后给予阿托伐他汀80 mg/d持续3 d,随后10 mg/d直至出院。对照组未给予他汀类药物治疗。主要终点事件为AKI发生和炎症标志物的改变。次要终点事件为院内和3个月随访期内全因病死率。结果治疗组患者AKI的发生率(13%)低于对照组AKI的发生率(15%),差异未见统计学意义(P=0.213)。两组患者的N端脑钠肽、超敏C-反应蛋白、胱抑素C水平比较差异未见统计学意义。同时,治疗组和对照组两组间的院内病死率(4.3%和3.8%,P0.999)和90 d随访全因病死率比较差异未见统计学意义。结论 AHF患者住院期间服用大剂量阿托伐他汀治疗可能是安全的,但对于降低炎症标志物和AKI是无效的。     

Body mass index and acute kidney injury in the acute respiratory distress syndrome

OBJECTIVES:: Obesity is increasingly encountered in intensive care units but the relationship between obesity and acute kidney injury is unclear. We aimed to evaluate whether body mass index was associated with acute kidney injury in the acute respiratory distress syndrome and to examine the association between acute kidney injury and mortality in patients with and without obesity. DESIGN:: Retrospective study. SETTING:: Massachusetts General Hospital and Beth Israel Deaconess Medical Center. PATIENTS:: Seven hundred fifty-one patients with acute respiratory distress syndrome. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Acute kidney injury was defined as meeting the "Risk" category according to modified Risk, Injury, Failure, Loss, End-stage criteria based on creatinine and glomerular filtration rate because urine output was only available on the day of intensive care unit admission. Body mass index was calculated from height and weight at intensive care unit admission. The prevalence of acute kidney injury increased significantly with increasing weight (p = .01). The odds of acute kidney injury were twice in obese and severely obese patients compared to patients with normal body mass index, after adjusting for predictors of acute kidney injury (age, diabetes, Acute Physiology and Chronic Health Evaluation III, aspiration, vasopressor use, and thrombocytopenia [platelets ≤ 80,000/mm]). After adjusting for the same predictors, body mass index was significantly associated with acute kidney injury (odds ratioadj 1.20 per 5 kg/m increase in body mass index, 95% confidence interval 1.07-1.33). On multivariate analysis, acute kidney injury was associated with increased acute respiratory distress syndrome mortality (odds ratioadj 2.76, 95% confidence interval 1.72-4.42) whereas body mass index was associated with decreased mortality (odds ratioadj 0.81 per 5 kg/m increase in body mass index, 95% confidence interval 0.71-0.93) after adjusting for mortality predictors. CONCLUSIONS:: In acute respiratory distress syndrome patients, obesity is associated with increased development of acute kidney injury, which is not completely explained by severity of illness or shock. Although increased body mass index is associated with decreased mortality, acute kidney injury remained associated with higher mortality even after adjusting for body mass index.     

Early diagnosis of acute kidney injury

PURPOSE OF REVIEW: The early detection of acute kidney injury may allow for timely preventive or therapeutic measures. This review discusses the role of traditional and novel biomarkers in early acute kidney injury diagnosis. RECENT FINDINGS: Detection of acute kidney injury relies on changes in serum creatinine and urea. These are not ideal and do not reflect genuine injury or real-time changes in kidney function. Several novel biomarkers have emerged for early detection of acute kidney injury. Cystatin C is sensitive to early and mild changes to kidney function. Neutrophril gelatinase-associated lipocalin is expressed early after injury and has value in predicting acute kidney injury after kidney transplant and cardiopulmonary bypass. Interleukin-18 has been detected early in acute kidney injury after kidney transplant, cardiopulmonary bypass and sepsis. Kidney injury molecule-1 is upregulated after ischemic/toxic injury and has the ability to predict the need for renal replacement therapy and mortality. While heterogeneous in their expression, these biomarkers may have value as a sequential 'panel' to aid in detecting, classifying and predicting the clinical course of acute kidney injury. SUMMARY: The early detection of acute kidney injury is a clinical and research priority. Traditional measures may contribute to delayed acute kidney injury diagnosis. Recent biomarkers have promise for earlier detection and for research into novel interventions.     

Effect of off-pump coronary artery bypass graft surgery on postoperative acute kidney injury and mortality

OBJECTIVE: Risk of mortality after cardiac surgery is associated with severity of acute kidney injury. The aim of this study is to examine the effect of off-pump coronary artery bypass surgery on the risk of postoperative acute kidney injury and its association with mortality. DESIGN: Observational cohort study. SETTING: Tertiary care center. PATIENTS: Some 10,061 patients underwent coronary artery bypass surgery (1998-2002), of which 1,365 patients underwent off-pump surgery. INTERVENTIONS: Acute kidney injury was defined as either requirement of dialysis or >/=50% decline in postoperative glomerular filtration rate but not requiring dialysis. We compared on- and off-pump surgeries and used propensity score matching to examine the effect of off-pump surgery on acute kidney injury and mortality. MEASUREMENTS AND MAIN RESULTS: We found that 2.6% on-pump and 1.2% off-pump patients developed acute kidney injury requiring dialysis among the 2,370 matched subjects (relative risk, 2.06; 95% confidence interval [CI], 1.36-3.36); 5.0% of on-pump patients suffered a >/=50% decline in glomerular filtration rate compared with 2.5% in off-pump group (relative risk, 2.00; 95% CI, 1.48-2.82). The mortality rate in the matched cohort was 2.3% for on-pump group vs. 0.6% in off-pump group (relative risk, 3.88; 95% CI, 2.29-9.50). Among matched patients with acute kidney injury, the risk of mortality was 13.14 (95% CI, 8.43-30.50) in patients requiring dialysis and 9.33 (95% CI, 4.83-19.00) in those with >/=50% decline in glomerular filtration rate but not requiring dialysis. CONCLUSIONS: Off-pump surgery is associated with a lower risk of developing acute kidney injury (regardless of its definition). The risk of mortality is incremental with worsening degrees of acute kidney injury. Lower risk of acute kidney injury may be one of the factors that offer a survival advantage after off-pump surgery.     

Earlier recognition of nephrotoxicity using novel biomarkers of acute kidney injury

Context. A broad range of drugs and chemicals are capable of evoking acute kidney injury, which is conventionally determined by rising serum creatinine concentrations. However there are important limitations to this approach, and there has been interest in alternative biomarkers that might provide a more sensitive and rapid means of detecting acute kidney injury. Most of the available clinical data have thus far been ascertained in patients requiring critical care or with acute sepsis. However, if a sensitive indicator of acute kidney injury were developed, then this could provide a significantly improved means of detecting the effects of acute drug or toxin exposure. Objective. To review the available data concerning potential biomarkers of acute kidney injury and to assess their relative strengths and weaknesses in comparison to existing methods based on serum creatinine concentrations. A large number of possible biomarkers have been proposed. Evidence for individual biomarkers is reviewed with a particular emphasis on those with potential application in clinical toxicology. Where available, comparative data are presented. Methods. There were 236 papers identified using Medline, Embase, and Google Scholar databases, of which 52 were considered directly relevant. Creatinine. Creatinine is subject to glomerular filtration and, to a lesser extent tubular secretion. Serum concentrations are an insensitive marker of acute kidney injury, and the speed of an increase from baseline depends on the magnitude of the acute injury and pre-existing kidney functional reserve. A wide range of inter-individual concentrations means that single time-point determinations are difficult to interpret, and acute kidney injury may not manifest as a detectable increase in serum creatinine concentrations until at least 24–48 h after the primary insult. Kidney enzymes. Enzymes are often localised to specific anatomical locations, and acute injury may cause a detectable increase in urinary activity due to up-regulated activity or leakage due to cell membrane disruption. Key examples include gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase (GST), and N-acetyl-glucosaminidase (NAG), which are found predominantly in the proximal tubule and urinary enzyme activity increases after acute exposure to heavy metals and other nephrotoxins .Neutrophil gelatinase-associated lipocalin. Neutrophil gelatinase-associated lipocalin (NGAL) is expressed by renal tubular epithelium, and a rise in urinary concentrations may provide an indicator of acute renal injury caused by any one of a broad range of provoking factors that is detectable before a rise in serum creatinine concentrations. Cystatin C. Serum and urinary cystatin C concentrations are closely related to kidney function and, for example, in acute tubular necrosis allow better prediction of the need for renal replacement therapy than serum creatinine concentrations. Kidney injury molecule 1. Kidney injury molecule 1 (KIM-1) is expressed in the proximal tubule in the setting of acute ischaemia. For example, urinary KIM-1 concentrations becomes detectable within 24 h of acute tubular necrosis. Urinary KIM-1 expression may be detected after exposure to a variety of nephrotoxic agents, even when serum creatinine concentrations do not increase, and this has been accepted by regulatory authorities as a sensitive biomarker of acute kidney injury during early drug development. Conclusions. Novel biomarkers appear capable of offering a more sensitive means of detecting acute kidney injury than existing approaches. Certain of these allow discrimination between the various mechanisms and anatomical site of acute injury. Ultimately, clinical assessment might incorporate a panel of different biomarkers, each informing on the integrated aspects of glomerular, tubular and interstitial function. Presence of biomarkers may in some cases detect mild or transient renal dysfunction that is presently undetected, and the clinical relevance needs further exploration. Whilst many potentially useful biomarkers have been proposed, comparatively few clinical data exist to support their validity in routine practice. Further prospective clinical studies are required to examine the validity of biomarkers after acute drug or toxin exposure, and to establish whether they might offer improved clinical outcomes in the setting of clinical toxicology.     

Biomarkers for the diagnosis of acute kidney injury

The identification of acute kidney injury relies on tests like blood urea nitrogen and serum creatinine that were identified and incorporated into clinical practice several decades ago. This review summarizes clinical studies of newer biomarkers that may permit earlier and more accurate identification of acute kidney injury. The urine may contain sensitive and specific markers of kidney injury that are present due to either impaired tubular reabsorption and catabolism of filtered molecules or release of tubular cell proteins in response to ischemic or nephrotoxic injury. Many potential markers have been studied. Promising injury markers in the urine include N-acetyl-beta-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and interleukin-18. New biomarkers of kidney injury hold the promise of substantially improving the diagnostic approach to acute kidney injury. Adequately powered clinical studies of multiple biomarkers are needed to qualify the biomarkers before they can be fully adopted in clinical practice. Once adopted, more sensitive biomarkers of acute kidney injury hold the potential to transform the care of patients with renal disease.     

Predictive and pathogenetic value of plasma biomarkers for acute kidney injury in patients with acute lung injury

OBJECTIVE: To identify biological and clinical predictors of acute kidney injury in subjects with acute lung injury. DESIGN: Secondary data analysis from a multicenter, randomized clinical trial. SETTING: Intensive care units in ten university medical centers. PATIENTS: A total of 876 patients enrolled in the first National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial. INTERVENTIONS: Study subjects were randomized to receive a low tidal volume ventilation strategy and pharmacologic therapy with ketoconazole or lisofylline in a factorial design. MEASUREMENTS AND MAIN RESULTS: We tested the association of baseline levels of interleukin-6, interleukin-8, interleukin-10, von Willebrand factor, tumor necrosis factor-[alpha], type I and II soluble tumor necrosis factor receptors (sTNFR-I and -II), protein C, plasminogen activator inhibitor-1 (PAI-1), surfactant protein-A, surfactant protein-D, and intracellular adhesion molecule-1 with subsequent acute kidney injury. Of 876 study participants who did not have end-stage renal disease, 209 (24%) developed acute kidney injury, defined as a rise in serum creatinine of >50% from baseline over the first four study days. The 180-day mortality rate for subjects with acute kidney injury was 58%, compared with 28% in those without acute kidney injury (p < .001). Interleukin-6, sTNFR-I, sTNFR-II, and PAI-1 levels were independently associated with acute kidney injury after adjustment for demographics, interventions, and severity of illness. A combination of clinical and biological predictors had the best area under the receiver operating characteristic curve, and the contribution of sTNFR-I and PAI-1 to this model was highly significant (p = .0003). CONCLUSIONS: Elevations in PAI-1, interleukin-6, and the sTNFRs in subjects with acute kidney injury suggest that disordered coagulation, inflammation, and neutrophil-endothelial interactions play important roles in the pathogenesis of acute kidney injury. The combination of these biological and clinical risk factors may have important and additive value in predictive models for acute kidney injury.     

Levels of neutrophil gelatinase-associated lipocalin in 2 patients with crush syndrome after a mudslide

Neutrophil gelatinase-associated lipocalin is one of the most promising biomarkers for the diagnosis of acute kidney injury. An increase in the level of neutrophil gelatinase-associated lipocalin is a good predictor of acute kidney injury and is associated with an increase in the serum level of creatinine. Two victims of a mudslide in Messina, Italy, initially had crush syndrome followed by development of acute kidney injury. The development of acute kidney injury is the second most common cause of death after large earthquakes and other natural disasters, but at the same time, crush-related acute kidney injury is one of the few life-threatening complications of crush injuries that can be reversed if diagnosed early and treated. In this case, measuring the level of neutrophil gelatinase-associated lipocalin enabled early diagnosis of acute kidney injury and anticipation of the changes in levels of conventional markers such as creatinine.     

Acute kidney injury in the intensive care unit according to RIFLE

OBJECTIVES: To apply the RIFLE criteria "risk," "injury," and "failure" for severity of acute kidney injury to patients admitted to the intensive care unit and to evaluate the significance of other prognostic factors. DESIGN: Retrospective analysis of the Riyadh Intensive Care Program database. SETTING: Riyadh Intensive Care Unit Program database of 41,972 patients admitted to 22 intensive care units in the United Kingdom and Germany between 1989 and 1999. PATIENTS: Acute kidney injury as defined by the RIFLE classification occurred in 15,019 (35.8%) patients; 7,207 (17.2%) patients were at risk, 4,613 (11%) had injury, and 3,199 (7.6%) had failure. It was found that 797 (2.3%) patients had end-stage dialysis-dependent renal failure when admitted to an intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:: Patients with risk, injury, and failure classifications had hospital mortality rates of 20.9%, 45.6%, and 56.8%, respectively, compared with 8.4% among patients without acute kidney injury. Independent risk factors for hospital mortality were age (odds ratio 1.02); Acute Physiology and Chronic Health Evaluation II score on admission to intensive care unit (odds ratio 1.10); presence of preexisting end-stage disease (odds ratio 1.17); mechanical ventilation (odds ratio 1.52); RIFLE categories risk (odds ratio 1.40), injury (odds ratio 1.96), and failure (odds ratio 1.59); maximum number of failed organs (odds ratio 2.13); admission after emergency surgery (odds ratio 3.08); and nonsurgical admission (odds ratio 3.92). Renal replacement therapy for acute kidney injury was not an independent risk factor for hospital mortality. CONCLUSIONS: The RIFLE classification was suitable for the definition of acute kidney injury in intensive care units. There was an association between acute kidney injury and hospital outcome, but associated organ failure, nonsurgical admission, and admission after emergency surgery had a greater impact on prognosis than severity of acute kidney injury.     

Le chlore est-il vraiment néphrotoxique ?

International guidelines recommend the early first-line use of crystalloids for fluid loading in the management of sepsis and septic shock. However, this recommendation is accompanied by a warning regarding the need to monitor blood chloride levels due to the possible involvement of chloride in the occurrence of metabolic acidosis and acute kidney injury by mechanism of vasoconstriction of the afferent arterioles. In the literature, numerous observational studies comparing sodium chloride (NaCl 0.9%) and so-called “balanced” solutions have yielded conflict results as regards with the possible causal relationship between hyperchloremia and occurrence of acute kidney injury or death. Only two large randomized, controlled studies in critically ill patients comparing NaCl 0.9% and a “balanced” solution (Ringer Lactate® and/or Plasma-Lyte®) failed to find any significant difference between the two groups in terms of frequency of acute kidney injury, need for renal replacement therapy or death. Future research should probably focus on identifying situations at risk, or on determining the quantities of crystalloids that it is appropriate to administer.     

Electroporation-mediated HGF gene transfection protected the kidney against graft injury

The annual rate of kidney graft loss caused by chronic allograft nephropathy (CAN) has not improved over the past decade. Recent reports suggest that acute renal ischemia results in development of CAN. The goal of the present study was to assess the renoprotective potential and safety of hepatocyte growth factor (HGF) gene transfer using a porcine kidney transplant warm ischemia injury model. Following left porcine kidney removal, 10 min of warm ischemic injury was intentionally induced. Next, the HGF expression vector or vehicle was infused into the renal artery with the renal vein clamped ex vivo, and electric pulses were discharged using bathtub-type electrodes. Kidney grafts were then transplanted after removing the right kidney. Histopathological examination of vehicle-transfected kidney transplant revealed initial tubular injury followed by tubulointerstitial fibrosis. In contrast, HGF-transfected kidneys showed no initial tubular damage and no interstitial fibrosis at 6 months post-transplant. We conclude that electroporation-mediated ex vivo HGF gene transfection protects the kidney against graft injury in a porcine model.