对比剂所致早期肾损伤时尿中性粒细胞明胶酶脂质运载蛋白的变化

目的：观察冠心病患者经皮冠状动脉腔内介入治疗术（PCI）后对比剂所致肾损伤时尿中性粒细胞明胶酶脂质运载蛋白（NGAL）的变化。方法：选择105例术前肾功能正常的行PCI术的冠心病患者,检测其手术前后不同时间点血肌酐（Scr）、尿NGAL水平和肾小球滤过率（GFR）。结果：术后有11例患者诊断为对比剂肾损伤,其尿NGAL水平异常较Scr提前至少24h。术后12h尿NGALROC曲线得出ROC曲线下的面积为0.824,AUC95%的可信区间为（0.735,0.913）。单变量分析示术前NGAL水平与GFR呈负相关,与年龄、血Scr浓度、血糖水平及糖尿病患病时间、血压水平及高血压患病时间呈正相关;术后尿NGAL水平与GFR呈负相关,与血Scr、手术时间呈正相关;多元Logistic回归分析显示血Scr及GFR是NGAL水平的独立影响因子。结论：尿NGAL对于冠心病患者PCI术后发生早期肾损伤具有良好的预测作用。     

Neutrophil Gelatinase-Associated Lipocalin as an Early Sign of Diabetic Kidney Injury in Children

Objective:

There is some evidence indicating that histopathological changes in type 1 diabetes mellitus (T1DM) emerge before onset of microalbuminuria. The aim of our study was to determine whether urine neutrophil gelatinase-associated lipocalin (NGAL) levels can be considered as an early sign of diabetic kidney injury.

Methods:

Urine NGAL (uNGAL) levels and urinary NGAL/creatinine ratio (uNGAL/Cr) were assessed in 76 patients with T1DM and compared with the findings of 35 healthy individuals. The relationship of uNGAL levels with diabetes duration, body mass index (BMI), serum lipids, HbA1c, and microalbuminuria was also evaluated.

Results:

Mean uNGAL (100.16±108.28 ng/mL) and uNGAL/Cr (118.93-117.97 ng/mg) levels in both microalbuminuric and non-microalbuminuric diabetic patients were found to be higher than those in the control group (uNGAL: 21.46±18.59 ng/mL and uNGAL/Cr: 32.1±51.48 ng/mg) (p=0.0001).

Conclusion:

Urine NGAL level increases in the very early phase of T1DM before microalbuminuria develops. The patients with T1DM should be considered to have diabetic kidney injury from the time of diagnosis on and preventive interventions need to be initiated at an early stage to preclude the progression to end-stage renal disease.     

Potential Role of Neutrophil Gelatinase‐Associated Lipocalin in Identifying Critically Ill Patients With Acute Kidney Injury Stage 2–3 Who Subsequently Require Renal Replacement Therapy

Delayed initiation of renal replacement therapy (RRT) in critically ill acute kidney injury (AKI) patients results in high mortality while too early RRT causes unnecessary risks of the treatment. Current traditional indications cannot clearly identify the appropriate time for initiating RRT. This prospective cohort study was conducted to determine the accuracy of using plasma neutrophil gelatinase‐associated lipocalin (pNGAL) and urine NGAL (uNGAL) in early identifying of the AKI patients who subsequently required RRT. Forty‐seven critically ill patients with AKI stage 2–3 who did not reach the traditional indications for RRT were enrolled in this study. The pNGAL, uNGAL, and other parameters were determined in each patient. The primary end point was RRT initiation according to the traditional indications within 3 days. The mean age of the patients was 63.0 ± 18.1 years. pNGAL could predict subsequent RRT requirements with area under ROC 0.813 (P < 0.001, 95%CI 0.66–0.90). The cut‐off point of 960 ng/mL provided sensitivity and specificity of 72.2 and 89.6%, respectively, and positive and negative predictive values of 81.25% and 83.8%, respectively. The uNGAL provided slightly lower significance of statistical parameters. The combination of pNGAL level of 960 ng/mL and APACHE II score of 20 improved statistical values. In conclusion, pNGAL is an excellent early biomarker for RRT initiation in critically ill patients with AKI stage 2–3. The pNGAL value of 960 ng/mL, alone or in combination with APACHE II score might be used as the early new indicator for early initiation of RRT in AKI stage 2–3 and this might improve patient survival.     

Urinary Neutrophil Gelatinase-Associated Lipocalin in Cirrhotic Patients with Acute Kidney Injury

Introduction and aim. It is well known that development of acute kidney injury (AKI) increases mortality in hospitalized cirrhotic patients; therefore many novel markers have been studied for early detection, differential diagnosis and prognosis in cirrhotic patients with AKI. The aim of the current work is to evaluate urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) as a diagnostic biomarker for different causes of acute kidney injury in liver cirrhosis and to assess it as a prognostic marker.Material and meth-ods. Out of 83 cirrhotic patients with AKI admitted between October 2015 and June 2016; 70 patients were included in this prospective study. Routine laboratory tests, uNGAL and fractional excretion of Na were obtained on admission. End points were death or improvement of kidney function and discharge.Results. The patients included in our study were 41 males and 29 females with mean age 54.27 ± 6.08 years. HCV was the etiology of cirrhosis in 69 cases while one had combined HBV and HCV infection. More than 50% of patients were classified as Child C. Causes of kidney injury were prerenal, hepatorenal syndrome (HRS) and intrinsic tubular injury (iAKI) in 39 patients (55.7%), 17 patients (24.3%) and 14 patients (20%) respectively. mean value of uNGAL in prerenal, HRS and iAKI was 21.70 ± 7.31, 115.53 ± 68.19 and 240.83 ± 116.94 ng/mg creatinine respectively. MELD above 20 and uNGL above 32 were predictors of mortality.Conclusion. A single baseline measurement of uNGAL level has the ability to determine type of kidney dysfunction in cirrhotic patients, perhaps accelerating management decisions and improving outcomes.     

Urinary Neutrophil Gelatinase-Associated Lipocalin Predicts Mortality and Identifies Acute Kidney Injury in Cirrhosis

Background

Kidney failure predicts mortality in patients with cirrhosis. Identification of kidney failure etiology and recognition of those at the highest mortality risk remains a challenge.

Aims

We hypothesized that urinary neutrophil gelatinase-associated lipocalin (uNGAL) predicts mortality and identifies hepatorenal syndrome (HRS) in patients with cirrhosis.

Methods

Prospectively enrolled patients with cirrhosis were investigated by uNGAL immunoblot upon hospital admission. Kidney failure type was determined blinded to NGAL measurements.

Results

One hundred eighteen patients were enrolled. Fifty-two (44?%) patients had normal kidney function, 14 (12?%) stable chronic kidney disease, 17 (14?%) prerenal azotemia, 20 (17?%) HRS, and 15 (13?%) intrinsic acute kidney injury (iAKI). Patients with HRS had uNGAL levels intermediate between prerenal azotemia [median (IQR) 105 (27.5–387.5) vs. 20 (15–45) ng/mL, p?=?0.004] and iAKI [325 (100–700), p??110?ng/mL (OR 6.05, 95?% CI 1.35–27.2) and HRS (OR 6.71, 95?% CI 1.76–25.5) independently predicted mortality, adjusting for age and serum creatinine?>1.5?mg/dL.

Conclusions

uNGAL strongly predicts short-term inpatient mortality in both unadjusted and adjusted models. Patients with HRS may have uNGAL levels intermediate between those with prerenal azotemia and iAKI. Further studies are needed to determine if uNGAL can improve discrimination of HRS from other types of acute kidney injury and predict short- and long-term cirrhosis outcomes.     

Urinary neutrophil gelatinase-associated lipocalin time course during cardiac surgery

Background:

NGAL is one of the most promising AKI biomarkers in cardiac surgery. However, the best timing to dose it and the reference values are still matter of discussion.

Aim of the Study:

We performed a uNGAL perioperative time course, to better understand its perioperative kinetics and its role in AKI diagnosis.

Setting of the Study:

San Raffaele University Hospital, cardiac surgery department.

Material and Methods:

We enrolled in this prospective observational study 19 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Based on preoperative characteristics, they were divided in low-risk and high-risk patients. uNGAL measurements were collected at pre-defined times before, during, and up to 24 hours after surgery.

Statistical Analysis:

Data were analysed by use of SAS 1999-2001 program or IBM SPSS Statistics.

Results:

In low-risk patients, uNGAL had the highest value immediately after general anesthesia induction (basal dosage: uNGAL: 12.20ng×ml^-1, IQR 14.00). It later decreased significantly (3.40 ng×ml^-1, IQR 4.80; P = 0.006) during CPB, and finally return to its original value 24 hours after surgery. In high-risk patients, uNGAL increased immediately after surgery; it had the highest value on ICU arrival (38,20 ng×ml^-1; IQR 133,10) and remained high for several hours. A difference in uNGAL levels between the two groups was already observed at the end of surgery, but it became statistically significant on ICU arrival (P = 0.002).

Conclusion:

This study helps to better understand the different kinetics of this new biomarker in low-risk and high-risk cardiac patients.     

尿中性粒细胞明胶酶相关脂质运载蛋白和白细胞介素-18对重症患者急性肾损伤的早期诊断价值

目的 探讨尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)和尿IL-18(uIL-18)对重症患者急性肾损伤(AKI)的早期诊断价值.方法 以我院ICU收治的92例危重症患者为观察对象,将1周内符合RIFLE诊断标准的AKI患者纳入AKI组(46例),对照组(46例)由匹配的非AKI患者构成.每日收集尿标本,持续1周.ELISA检测uNGAL和uIL-18水平.用受试者工作特征曲线(ROC)评价uNGAL、uIL-18和血肌酐(SCr)对AKI的诊断作用.结果 与AKI诊断前3天比较,AKI诊断前2天患者uNGAL明显增高(P<0.05),但uIL-18和SCr无明显改变(P值均>0.05);AKI诊断前1天AKI患者uNGAL和uIL-18明显增高(P值均<0.05),但SCr无明显改变(P>0.05);观察期间对照组uNGAL、uIL-18和SCr均无明显变化(P值均>0.05).AKI诊断前3天uNGAL、uIL-18和SCr对AKI均无诊断作用;AKI诊断前2天uNGAL的ROC曲线下面积为0.840(95%CI 0.672～1.009,P<0.05),对AKI具有诊断作用,而uIL-18和SCr均无诊断作用;AKI诊断前1天uNGAL和uIL-18的ROC曲线下面积分别为0.830(95%CI 0.711～0.950,P<0.05)和0.818(95%CI 0.697～0.938,P<0.05),对AKI具有诊断作用,而SCr无诊断作用.结论 uNGAL和uIL-18对重症患者AKI可能具有早期诊断价值.     

中性粒细胞明胶酶相关脂质运载蛋白对轻中度肾衰竭患者对比剂急性肾损伤的预测价值

目的:评价血浆中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated li-pocalin,NGAL)在对比剂急性肾损害(contrast induced acute kidney injury,CIAKI)早期诊断价值。方法:连续入选拟行冠状动脉造影及支架植入术的患者。包括稳定型心绞痛及除急性ST段抬高性心肌梗死外的急性冠状动脉综合征患者;按照适合中国人的肾脏疾病饮食调整公式(Modified diet in renal dis-ease,MDRD)公式评价肾功能,选择30≤eGFR<90 mL.min-1.1.73 m-2的患者。CIAKI定义为:PCI术后48～72 h,SCr升高44.2 mmol/L(0.5 mg/dL)或升高25%。术前及术后4 h血浆NGAL采用ELISA方法检测,评价NGAL对CIAKI的预测价值。结果:共入选患者311例,其中39例(12.5%)患者发生了CIAKI。术前及术后4 h血浆NGAL水平的曲线下面积(area under the ROC curve,AUC)分别为(0.567,95%CI:0.465～0.668,P=0.210)和(0.662,95%CI:0.565～0.758,P=0.002)。结论:血浆NGAL可以作为CIAKI的早期诊断标志物,阴性诊断价值更大。     

冠脉搭桥术后急性肾损伤临床分析

【】目的：探讨冠脉搭桥术(CABG)后急性肾损伤(AKI)的相关因素,分析AKI对患者预后的影响。方法：回顾性分析2012年1月~2013年12月河南科技大学第一附属医院227例CABG患者的临床资料,根据患者术后是否出现AKI分为AKI组和非AKI组,应用单因素分析和Logistic回归分析CABG后AKI相关因素,并分析AKI对患者预后的影响。结果：两组患者手术时间、应用主动脉内球囊反搏泵(IABP)、应用呋塞米、多巴胺、肾上腺素、硝酸甘油、米力农、胺碘酮、羟乙基淀粉及前列地尔比较,差异具有统计学意义,可能与CABG后AKI有关,经过Logistic回归分析显示手术时间(P=0.004)、应用呋塞米(P=0.001)、肾上腺素(P=0.035)与CABG后AKI有关,AKI组患者术后机械通气时间、住ICU时间、住院时间较非AKI组长,低氧血症发生率、二次插管率高,差异具有统计学意义。而术后30天内死亡率、心律失常发生率差异无统计学意义。结论：手术时间、应用呋塞米、肾上腺素是CABG后AKI的独立危险因素,AKI患者机械通气时间、住ICU时间、住院时间延长,低氧血症发生率、二次插管率高。     

Statins and Contrast-induced Acute Kidney Injury with Coronary Angiography

BackgroundContrast-induced acute kidney injury is an adverse outcome resulting from radiocontrast medium exposure during coronary angiography and percutaneous coronary intervention.MethodsA systematic search was conducted to retrieve studies that investigated the impact of statin exposure before coronary angiography or percutaneous coronary intervention on the development of contrast-induced acute kidney injury. The primary outcome was the development of contrast-induced acute kidney injury. We separately analyzed statin/placebo comparisons and high-/low-dose statin comparisons.ResultsFifteen randomized controlled trials met inclusion criteria: 11 studies with statin-naïve subjects, 2 studies with chronic statin users, and 2 studies with unspecified prior statin exposure. Statin exposure reduced the risk of contrast-induced acute kidney injury relative to placebo (relative risk [RR] 0.63, P = .01) with a nonsignificant reduction in the need for hemodialysis (RR 0.25, P = .08). This benefit was also observed in high-dose versus low-dose statin trials (RR 0.46, P = .004), in statin-naïve patients (RR 0.53, P <.0001), and with all studied statins. Higher statin exposure reduced contrast-induced acute kidney injury in patients with acute coronary syndromes compared with placebo or low-dose statins (RR 0.49, P <.00001), with no significant benefit among patients undergoing elective procedures (RR 0.86, P = .50). Subgroup analyses confirmed the benefit of statins in patients with diabetes, chronic kidney disease, congestive heart failure, and those receiving >140 mL of contrast dye.ConclusionStatin therapy is effective at reducing the risk of contrast-induced acute kidney injury. It should thus be considered, at least on a short-term basis, for patients at increased risk of this complication.     

When Prevention is Truly Better than Cure: Contrast-Associated Acute Kidney Injury in Percutaneous Coronary Intervention

Contrast-associated acute kidney injury (CA-AKI) is a fairly frequent complication of cardiovascular angiography and percutaneous coronary intervention (PCI). The risk is significantly higher in patients with advanced chronic kidney disease (CKD). Prevention is the only option for avoiding the significant morbidity and mortality associated with CA-AKI. This review provides a concise and clinically directed appraisal of the latest pre-procedural and peri-procedural strategies to minimize the risk of CA-AKI in all patients undergoing PCI. By broadly implementing these evidence-based care bundles, we can dramatically improve outcomes in this vulnerable patient population.     

Neutrophil Gelatinase-Associated Lipocalin and Acute Kidney Injury after Cardiac Surgery: The Effect of Baseline Renal Function on Diagnostic Performance

Background and objectives: Neutrophil Gelatinase-Associated Lipocalin (NGAL) is rapidly released by renal tubules after injury, potentially allowing early identification of acute kidney injury (AKI) after cardiac surgery. However, the diagnostic performance of NGAL has varied widely in clinical studies, and it remains unknown what factors modify the relationship between NGAL and AKI. We hypothesized the relationship between urinary NGAL and AKI would vary with baseline renal function, allowing a stratified analysis to improve diagnostic performance of this novel biomarker.Design, setting, participants, & measurements: We performed a prospective observational study in 426 adult cardiac surgical patients. Urinary NGAL was serially determined, commencing preoperatively and continuing 24 hours postoperatively. AKI was defined as increase in serum creatinine from baseline by either >50% or >0.3 mg/dl within 48 hours postoperatively. Patients were stratified by baseline estimated GFR (eGFR). NGAL levels were compared between patients with and without AKI and diagnostic characteristics determined according to baseline eGFR.Results: In patients with baseline eGFR ≥60 ml/min, urinary NGAL was higher at all postoperative time points in patients who developed AKI compared with those who did not. In patients with baseline eGFR <60 ml/min, urinary NGAL did not differ at any time between those who did and those who did not develop AKI. Postoperative NGAL best identified AKI in patients with baseline eGFR 90 to 120 ml/min.Conclusions: The relationship between urinary NGAL and AKI after cardiac surgery varies with baseline renal function, with optimal discriminatory performance in patients with normal preoperative function.Acute Kidney Injury (AKI) is a common complication after cardiac surgery, with reported incidence varying from 20% to 50% depending on the definition used (1–4). Early detection of injury is desirable to facilitate early intervention aimed at limiting associated morbidity and mortality. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is rapidly released by renal tubules in response to injury, and an acute rise in urinary NGAL has been reported to accurately identify evolving AKI in both pediatric and adult populations within 2 to 8 hours of cardiac surgery (5–9). However, other studies have found urinary NGAL to have only modest discriminant ability for AKI after cardiac surgery (3,10). Studies reporting excellent discriminant ability have generally excluded patients with preoperative renal dysfunction, whereas those studies reporting a more modest performance have included patients with a heterogeneous mix of baseline renal function. Although it is unknown whether baseline renal function modifies the relationship between NGAL and AKI, the existence of such a relationship may contribute to the limited predictive ability in these studies. Although NGAL is proposed as a real-time marker of acute renal injury rather than renal function, the nonlinear relationship between GFR and serum creatinine may mean that a relatively larger injury, producing a larger reduction in GFR, is required to cause a rise in serum creatinine sufficient to meet diagnostic criteria for AKI in a patient with normal baseline GFR. Conversely, a much smaller injury (and smaller incremental reduction in GFR) may be sufficient to cause a rise in creatinine that would diagnose AKI in a patient with impaired GFR at baseline. If true, the diagnostic utility of urinary NGAL for a creatinine-based diagnosis of AKI may be enhanced using an approach stratified by baseline renal function. We have previously reported a modest performance of urinary NGAL for early identification of evolving AKI in a large, unselected adult population undergoing cardiac surgery, with a wide range of baseline renal function. In this posthoc analysis we sought to investigate this potential source of effect modification to the relationship between NGAL and postoperative AKI. We hypothesized that the relationship between postoperative urinary NGAL and AKI would vary with baseline renal function, measured by estimated GFR (eGFR). We further hypothesized that the diagnostic performance of NGAL for postoperative AKI would be improved using an analysis stratified by baseline function, allowing the use of different diagnostic thresholds.     

经皮冠状动脉介入治疗后两种对比剂诱发的急性肾损伤诊断标准的应用比较

目的:评估两种对比剂诱发的急性肾损伤(CI-AKI)诊断标准在行经皮冠状动脉介入治疗(PCI)患者的临床特征及术后不良事件相关性差异。方法:回顾性分析2013年1月至12月于我院行PCI的患者共10394例。比较欧洲泌尿生殖放射学会CI-AKI诊断标准[血清肌酐绝对值升高≥44.2μmol/L(0.5 mg/dl),或较基线值升高≥25%,简写为CI-AKI 25%标准]和改善全球肾病预后组织CI-AKI诊断标准[血清肌酐绝对值升高≥26.5μmol/L(0.3 mg/dl),或较基线值升高≥50%,简写为CI-AKI 50%标准]诊断的CI-AKI发生率及与PCI后2年内主要心脑血管不良事件(MACCE,包括死亡、心肌梗死、血运重建、支架内血栓、脑卒中的复合终点事件)发生风险的差别。结果:10394例患者中,采用CI-AKI 25%标准诊断的CI-AKI为936例(9.0%),而采用CI-AKI 50%标准诊断的CI-AKI患者为206例(2.0%),P<0.001。与CI-AKI 50%标准诊断的CI-AKI患者相比,CI-AKI 25%标准诊断的CI-AKI患者,其估算的肾小球滤过率(eGFR)更高,而术前血清肌酐更低,慢性肾脏病(CKD)1期的患者比例较高(P均<0.05)。在随访期间,共有1240例(11.9%)患者发生MACCE。CI-AKI 25%标准和CI-AKI 50%标准诊断的患者的MACCE发生率差异无统计学意义(9.9%vs.11.7%,P=0.463)。COX多因素回归分析显示两种CI-AKI诊断标准确定的CI-AKI均不是MACCE的独立预测因素(P>0.05)。结论:为避免在肾功能正常的患者中过度定义CI-AKI,CI-AKI 50%标准更适用于临床中筛选出肾功能损伤高危的患者;两种标准诊断的CI-AKI均与PCI后2年MACCE的发生无显著相关。     

Novel Urinary Biomarkers in Detecting Acute Kidney Injury,Persistent Renal Impairment,and All-Cause Mortality Following Decongestive Therapy in Acute Decompensated Heart Failure

BackgroundNew urinary biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18), are proposed to allow a more reliable early diagnosis and prognosis of acute kidney injury (AKI) in acute decompensated heart failure (ADHF). Our aim was to compare the predictive value of urinary NGAL, KIM-1, and IL-18 for the occurrence of AKI, persistent renal impairment, and mortality in ADHF.Methods and ResultsEighty-three patients admitted for ADHF were analyzed. Urinary creatinine (Cr), NGAL, KIM-1, and IL-18 were measured at baseline. Serum Cr was measured daily during the next 4 days and again at outpatient follow-up after 6 months. Mortality data were prospectively collected. Urinary NGAL, KIM-1, and IL-18 were modestly correlated with each other (Spearman ρ ≤0.61) and poorly correlated with estimated glomerular filtration rate (eGFR; Spearman ρ ≤0.28). None predicted AKI, defined as a 25% decrease in eGFR, during the index hospitalization, but urinary IL-18/Cr was the strongest predictor of persistently elevated serum Cr ≥0.3 mg/dL after 6 months compared with baseline (area under the receiver operating characteristic curve 0.674; P = .013). Urinary IL-18 was also significantly associated with all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.16–1.87; P = .001).ConclusionsLike urinary NGAL, urinary KIM-1 and IL-18 are relatively modest predictors of AKI in ADHF. Among these novel renal biomarkers examined, further investigations regarding the prognostic value of urinary IL-18 are warranted.     

High-risk Acute Coronary Syndrome Patients with Non-ST-Elevation Myocardial Infarction: Definition and Treatment

Introduction  Early risk stratification of patients with acute coronary syndromes (ACS), unstable angina, or non-ST-elevation myocardial infarction ensures patients receive appropriate care. Materials and methods  Many risk-stratification models have been developed to identify high-risk ACS patients who would benefit most from an early invasive strategy and to determine patients at greater risk for bleeding complications. Although high-risk patients seem to benefit most from a combination of aggressive antithrombotic and early invasive therapies, stratification for risk of bleeding also helps in the choice and dosing of appropriate medical therapy. Results  The effective use of glycoprotein IIb/IIIa inhibitors, in particular, is dependent on accurate risk assessment, whereas the risk-to-benefit ratio of direct thrombin inhibitors in high-risk versus low-risk patients as part of an initial therapy plan requires clarification. Nevertheless, use of the same anticoagulant throughout the care pathway may reduce the rates of death or recurrent myocardial infarction, and bleeding complications.