尿胱抑素C预测非少尿型ATN近期结局的临床应用价值

目的：探讨尿胱抑素C预测非少尿型急性肾小管坏死（acutetubular necrosis，ATN）近期是否需要肾替代治疗（renal replacement therapy，RRT）的临床应用价值。方法：用ELISA法检测64例非少尿型ATN患者（均在发病3日内）的尿胱抑素C水平，观察此64例患者15日后的结局，根据有否行RRT分为RRT组及非RRT组，比较2组进入研究时的血清肌酐水平、尿流速、LLANO积分、尿胱抑素C水平，并比较后两者的接收者工作特征（receiver operating characteristic，ROC）曲线。结果：21例进入RRT纽，余43例为非RRT组。2纽进入研究时的血清肌酐及尿流速比较，差异均无统计学意义（均为P〉0．05）；而进入研究时，RRT组的尿胱抑素C水平比非RRT组显著升高（P〈0．01）；2组的LLANO积分比较差异亦有统计学意义（P〈0．05）。通过比较两者的ROC曲线，前者的敏感度、特异度均高于后者。结论：尿胱抑素C在近期结局不同的非少尿型ATN患者中存在明显的差异，可作为预测此类患者是否需要行RRT治疗的指标，其敏感度及特异度均高于LLANO积分，具有重要的临床应用价值。     

Tubular proteinuria and enzymuria following open heart surgery

Objective We investigated the effect of cardiac surgery on a marker of tubular damage, an enzyme called neutral endopeptidase (NEP), and on a marker of tubular function, retinol binding protein (RBP). Markers of tubular damage or function are useful in the early detection of acute renal failure and help identify the risk factors for this disease. We also examined if colloid interfered with NEP measurement.Design A controlled prospective cohort study.Setting A teaching cardio-thoracic unit in London, England.Patients and participants Thirty-four patients underwent cardiac surgery. Eight patients waiting for cardiac surgery acted as controls.Interventions Twenty-five patients had coronary artery bypass graft, four patients had valve replacements, one patient had a coronary artery bypass graft with a valve replacement and one patient had a left ventricular aneurysm repair.Measurements and Results Neutral endopeptidase was measured in all the patients and controls. In separate subgroups RBP (n=5) and Gelofusine use (n=12) were recorded. Urine samples were collected pre-operatively, 3 h, 1 and 4 days post-operatively. NEP rose significantly (p<0.05) after cardiac surgery compared with the control population. RBP also rose significantly (p<0.05) after cardiac surgery. NEP correlated with RBP 3 h post-operatively (p<0.05, r²=0.97). There was no correlation between the amount of Gelofusine given and NEP excretion.Conclusion Excretion of NEP and RBP were both increased after cardiac surgery. Colloid did not affect the excretion of NEP, although in other studies it has affected the excretion of RBP. This may make NEP excretion a better index of acute and impending renal damage following cardiac surgery.Partial funding was obtained via a research vacation scholarship from the Wellcome Trust. (JB)Work was carried out at The Middlesex Hospital, London.     

Prucalopride-associated acute tubular necrosis

We report the first case of acute renal failure secondary to prucalopride, a novel agent for the treatment of chronic constipation. The 75 years old male patient was initiated on prucalopride after many failed treatments for constipation following a Whipple's procedure for pancreatic cancer. Within four months of treatment his creatinine rose from 103 to 285 μmol/L(e GFR 61 decrease to 19 m L/min per 1.73 m2). He was initially treated with prednisone for presumed acute interstitial nephritis as white blood casts were seen on urine microscopy. When no improvement was detected, a core biopsy was performed and revealed interstitial fibrosis and tubular atrophy. The presence of oxalate and calcium phosphate crystals were also noted. These findings suggest acute tubular necrosis which may have been secondary to acute interstitial nephritis or hemodynamic insult. The use of prednisone may have suppressed signs of inflammation and therefore the clinical diagnosis was deemed acute interstitial nephritis causing acute tubular necrosis. There are no previous reports ofprucalopride associated with acute renal failure from the literature, including previous Phase Ⅱ and Ⅲ trials.     

Animal models of acute tubular necrosis

The evaluation and management of acute renal failure in the ICU patient remains a formidable task because of the complexity of this condition. Clinical and physiologic assessment and complementing laboratory and imaging tests are currently insufficient to differ between true renal parenchymal damage (acute tubular necrosis; it is important to realize that this term does not necessarily imply widespread injury, because whole organ dysfunction in humans has often been associated with very limited parenchymal cellular necrosis) and prerenal azotemia (decreased renal blood flow with altered glomerular hemodynamics and subsequently diminished glomerular filtration, without significant epithelial cell injury). Moreover, tubular damage and altered glomerular hemodynamics may coexist or lead to each other, and their relative contribution to the evolving renal dysfunction has not been unequivocally established. The limited data regarding the renal pathology of such patients and the scant information about human morphologic and functional correlates further undermine our knowledge about diagnostic and therapeutic approaches to these patients. Advanced techniques are critically needed to establish noninvasively the dynamic status of renal parenchymal microcirculation and the distribution of intrarenal oxygenation and to identify evolving cellular energy depletion and tubular cell damage. A few technologies are potentially promising, such as blood oxygen level dependent magnetic resonance imaging, positron emission tomography, and kidney injury molecule-1 detection in patients' urine. Because of the difficulties in analyzing the pathophysiology in humans, clinicians continue to rely largely on animal models to guide understanding and rationale for the identification of therapeutic targets. Data from such animal studies are complemented by studies in isolated perfused kidneys, isolated tubules, and tubular epithelial cell cultures. In this report, we summarize some concepts of acute tubular necrosis that have evolved as a result of these studies, evaluate available animal models, and underscore controversies regarding experimental acute tubular necrosis.     

Diagnosis and management of acute tubular necrosis

The term acute tubular necrosis refers to those forms of acute renal failure that occur in association with ischemic or hypoxic injury or exposure to nephrotoxic substances. This article discusses the various alternative classifications that are based solely on the clinical setting in which the acute renal failure occurs, and the types of therapies used in the management of them.     

成纤维细胞特异性蛋白-1在急性肾小管坏死病变中的表达及临床意义

目的检测成纤维细胞特异性蛋白-1(FSP-1)在急性肾小管坏死(ATN)病变肾组织及尿沉渣中的表达,并分析其临床意义。方法收集ATN患者10例,新月体肾炎2例为阳性对照,正常肾组织3例为阴性对照,采用免疫组化和免疫荧光法检测FSP-1、CD68(巨噬细胞标志物)在肾组织中的表达,并观察ATN患者尿沉渣涂片中FSP-1的表达。收集6例健康志愿者的晨尿标本作为阴性对照。结果正常肾组织肾间质小血管偶见FSP-1表达,CD68染色阴性。阳性对照新月体肾炎患者肾小球细胞性新月体及纤维细胞性新月体中FSP-1呈散在阳性分布,肾小管间质中亦可见FSP-1阳性细胞。ATN患者肾组织FSP-1阳性细胞位于损伤、再生的肾小管周围及肾小管管腔中,部分肾小管上皮细胞也见FSP-1阳性表达。肾组织病变严重的ATN患者肾脏及尿沉渣涂片中FSP-1阳性细胞明显增多。尿沉渣FSP-1阳性细胞数与肾脏FSP-1阳性细胞数呈正相关(r=0.793,P=0.006)。FSP-1与CD68的阳性表达部位不重叠。健康志愿者的尿沉渣涂片中未见FSP-1阳性细胞表达。结论 ATN患者肾组织中可见FSP-1阳性细胞的浸润及FSP-1在肾小管上皮的表达,与尿沉渣FSP-1阳性细胞数呈正相关,FSP-1有望成为反映肾小管急性损伤的生物学标志物。     

Clara细胞分泌蛋白检测对急性肾小管坏死诊断的意义

目的：探讨Clara细胞分泌蛋白（CCSP）检测在诊断急性肾小管坏死（ATN）中的意义，以提高ATN的早期诊断率。方法：选取4例ATN患者肾活检组织，以原发性慢性肾小球肾炎[膜性肾病（MN）／微小病变（MCD）n=4]患者的肾脏及4例正常肾组织作为对照，应用免疫组化和免疫荧光方法检测肾脏组织的CCSP表达。选择10例ATN、10例原发性慢性肾小球炎（MN／MCD）和15例正常对照，采用ELISA法测定其血、尿CC16浓度。结果：免疫组化和免疫荧光结果显示,ATN组、MN／MCD组及正常对照组，肾小球中均无CCSP表达，肾小管上皮细胞有CCSP表达。而其中ATN患者则因肾小管受损，其肾小管上皮细胞CCSP表达较另2组下降。ATN患者起病期与肾功能恢复期间尿CC16差异有统计学意义[（1624．45±1119．11）ng／mL比（472．60±289．36）ng／mL，P〈0．01]。尿CC16浓度在ATN起病期显著增高，与正常对照组、MN／MCD组间差异有统计学意义（P〈0．05）。结论：检测肾组织中CCSP有助于判断患者的肾小管功能．特别是近端肾小管受损情况：尿CC16浓度测定可作为急性肾小管损伤的指标，且与受检者肾组织中CCSP表达相吻合。     

Prognostic significance of survivin and tumor necrosis factor-alpha in adult acute lymphoblastic leukemia

ObjectivesAcute lymphoblastic leukemia (ALL) is an aggressive cancer especially in adults as only 20–40% are cured with current treatment regimens.Design and methodsWe measured survivin and tumor necrosis factor-alpha (TNF-α) in serum of 30 ALL patients before and after induction therapy and compared to 30 age and sex matched normal adults.ResultsSurvivin at cutoff value 15.18 pg/mL was detected in all ALL patients before therapy but in only 83.33% after therapy and not detected in the control group; P < 0.001. However TNF-α at cutoff value 60.05 pg/mL was detected in 90% ALL patients before therapy and 86.6% after therapy that was significantly higher than the control group (20%); P < 0.001. Survivin showed a significant positive correlation with TNF-α (P < 0.05), bone marrow blast cells (P < 0.01), peripheral blast cells (P < 0.05) and Philadelphia chromosome (P < 0.01).ConclusionsSurvivin may have an important role in the development of acute leukemia and it could serve as a significant prognostic marker.     

降钙素原对急性百草枯中毒患者预后的作用

目的 分析急性百草枯中毒(PQ)患者降钙素原(PCT)水平变化特点,探讨其与病情严重程度和预后的关系.方法 选取2013年3月至2014年3月郑州大学第一附属医院急诊医学部收治的急性百草枯中毒患者128例进行回顾性分析,根据中毒后28 d预后分为生存组和死亡组.详细记录患者的中毒剂量、尿百草枯浓度、中毒距就诊时间、中毒距血液灌流时间等一般资料.在患者入院第1,3,7天分别测其血清PCT等生化指标.分析生存组和死亡组PCT指标的动态变化,探讨PCT对急性百草枯中毒患者病情评估及预后的预测价值.结果 128例患者存活72例,死亡56例.其中,有90例患者入院第1天测得PCT水平有不同程度升高,最后死亡48例.生存组和死亡组比较:死亡组患者PCT动态水平与生存组相比差异具有统计学意义[1 d:(0.96±0.13)vs.(0.08±0.01),3d:(1.12±0.14)vs.(0.28±0.05),7d:(1.22±0.14)vs.(0.20±0.03),P＜0.01];动态观察发现,死亡组PCT呈逐步上升趋势,生存组于第3天达高峰后呈下降趋势.病程早期PCT水平与中毒剂量、尿百草枯浓度、CRP、WBC、ALT、CR之间有显著相关性(相关系数r分别为0.794、0.724、0.723、0.332、0.700、0.414,P均＜0.01).结论 急性百草枯中毒后早期PCT水平升高与中毒剂量及尿百草枯浓度呈显著相关性,可作为反映百草枯中毒严重程度的指标;动态监测PCT水平变化,对了解病情发展、预后评估具有重要意义.     

液体反应性对急性呼吸窘迫综合征的预后价值

目的 探讨液体反应性对急性呼吸窘迫综合征(ARDS)患者的预后价值.方法 本前瞻性临床研究在浙江中医药大学附属第二医院ICU进行.59例在接受机械通气的ARDS患者,采用脉搏波指示连续心排血量( PiCCO)技术测定其每搏输出量变异(SVV),根据SVV值将患者分为液体有反应组(SVV≥15％)和液体无反应组(SVV＜15％);比较两组患者28 d生存率、ICU住院时间、机械通气时间的差异;Kaplan-Meier法分析患者累积生存情况;采用Logistic回归分析SVV与患者28 d生存率的关系.结果 与液体无反应组比较,液体有反应组患者28d生存率明显增高(85.3％ vs.56.0％,P=0.012),ICU住院时间明显减少[((13.1±5.2) d vs.(21.6±9.0)d,P=0.008)、机械通气时间明显缩短[(11.4±5.3) d vs.(18.3±4.9)d,P=0.022];Logistic回归分析显示:SVV＜ 15％显著增高ARDS患者28d死亡风险(OR=4.82; 95％ CI:2.67～11.71,P=0.009).结论 以SVV为基础的液体反应性可以作为ARDS患者的预后指标.     

Prognostic value of mitochondrial aspartate aminotransferase in acute myocardial infarction

In 112 prospectively selected patients suffering from acute myocardial infarction (AMI), the serum CK, CK-MB, LD, HBD, AST and m-AST were determined from the time of admission to hospital and every 12 hours for three days in succession. Sixteen of the enrolled patients died due to complications which arose within the first four days of hospitalization while the rest had a favourable outcome. All enzyme activities were determined at 37 degrees C using routine methods; m-AST was measured using an immunochemical method. The statistical analysis of the results demonstrated that 12 hours after admission, serum m-AST and m-AST/AST ratio were significantly higher in the group of non-survivors compared with patients with a favourable prognosis. No significant differences in CK-MB were observed between survivors and non-survivors during the entire period. True and false positive rates were calculated for these and the other enzymes. An optimum decision level of 34 IU/L was chosen for m-AST and 10% for the m-AST/AST ratio. This gave a percentage of correctly classified patients, after 12 and 24 hours, of 74.9% and 91.9%, respectively. In conclusion, the immunochemical determination of m-AST in patients with AMI seems to be an early prognostic index which is able to distinguish patients with unfavourable outcome.     

Prognostic value of brain natriuretic peptide in acute pulmonary embolism

Introduction

The relationship between brain natriuretic peptide (BNP) increase in acute pulmonary embolism (PE) and the increase in mortality and morbidity has frequently been suggested in small studies but its global prognostic performance remains largely undefined. We performed a systematic review and meta-analysis of data to examine the prognostic value of elevated BNP for short-term all-cause mortality and serious adverse events.

Methods

The authors reviewed PubMed, BioMed Central, and the Cochrane database and conducted a manual review of article bibliographies. Using a prespecified search strategy, we included a study if it used BNP or N-terminal pro-BNP biomarkers as a diagnostic test in patients with documented PE and if it reported death, the primary endpoint of the meta-analysis, in relation to BNP testing. Studies were excluded if they were performed in patients without certitude of PE or in a subset of patients with cardiogenic shock. Twelve relevant studies involving a total of 868 patients with acute PE at baseline were included in the meta-analysis using a random-effects model.

Results

Elevated BNP levels were significantly associated with short-term all-cause mortality (odds ratio [OR] 6.57, 95% confidence interval [CI] 3.11 to 13.91), with death resulting from PE (OR 6.10, 95% CI 2.58 to 14.25), and with serious adverse events (OR 7.47, 95% CI 4.20 to 13.15). The corresponding positive and negative predictive values for death were 14% (95% CI 11% to 18%) and 99% (95% CI 97% to 100%), respectively.

Conclusion

This meta-analysis indicates that, while elevated BNP levels can help to identify patients with acute PE at high risk of death and adverse outcome events, the high negative predictive value of normal BNP levels is certainly more useful for clinicians to select patients with a likely uneventful follow-up.     

经颅多普勒超声检测对脑出血急性期预后判断的价值

【目的】探讨脑出血病人脑血流动力学有关参数与CT脑血肿量和GCS评分的相关性,评价TCD对急性期脑出血预后判断价值。【方法】对起病≤12 h病人,头部CT确诊的78例幕上单侧自发性脑出血病人通过经颅多普勒(TCD)进行双侧大脑中动脉TCD检测和GCS评分。【结果】TCD双侧大脑中动脉PI值均明显升高,Vd及Vm呈现降低,Vs无明显变化;TCD有关参数与CT血肿量pearson相关系数分析,aPi和uPi P值均<0.001,Vd、Vs和Vm与CT血肿量大小无统计学显著性差异;ICP(颅内压)升高时,TCD最直接的特征是脑血流频谱的变化:即典型的"三峰形"频谱消失,出现收缩峰高尖、S1和S2峰融合、舒张期前切迹加深、搏动增加等;TCD参数与GCS评分pearson相关系数分析,PI值呈负性相关,并具有统计学显著性差异(P<0.0001)。【结论】TCD对急性期脑出血病人脑血流动力学的检测显示:及时反映颅内高压程度和脑血流灌注,为脑出血早期预后判断和及时调整治疗方案提供了简便有效方法。