Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function

To better understand the diagnostic and predictive performance of urinary biomarkers of kidney injury, we evaluated γ-glutamyltranspeptidase (GGT), alkaline phosphatase (AP), neutrophil-gelatinase-associated lipocalin (NGAL), cystatin C (CysC), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in a prospective observational study of 529 patients in 2 general intensive care units (ICUs). Comparisons were made using the area under the receiver operator characteristic curve (AUC) for diagnosis or prediction of acute kidney injury (AKI), dialysis, or death, and reassessed after patient stratification by baseline renal function (estimated glomerular filtration rate, eGFR) and time after renal insult. On ICU entry, no biomarker had an AUC above 0.7 in the diagnosis or prediction of AKI. Several biomarkers (NGAL, CysC, and IL-18) predicted dialysis (AUC over 0.7), and all except KIM-1 predicted death at 7 days (AUC between 0.61 and 0.69). Performance was improved by stratification for eGFR or time or both. With eGFR <60?ml/min, CysC and KIM-1 had AUCs of 0.69 and 0.73, respectively, within 6?h of injury, and between 12 and 36?h, CysC (0.88), NGAL (0.85), and IL-18 (0.94) had utility. With eGFR >60?ml/min, GGT (0.73), CysC (0.68), and NGAL (0.68) had the highest AUCs within 6?h of injury, and between 6 and 12?h, all AUCs except AP were between 0.68 and 0.78. Beyond 12?h, NGAL (0.71) and KIM-1 (0.66) performed best. Thus, the duration of injury and baseline renal function should be considered in evaluating biomarker performance to diagnose AKI.     

Value of urine IL-8, NGAL and KIM-1 for the early diagnosis of acute kidney injury in patients with ureteroscopic lithotripsy related urosepsis

PurposeTo investigate the clinical value of urine interleukin-18 (IL-8), neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) for the early diagnosis of acute kidney injury (AKI) in patients with ureteroscopic lithotripsy (URL) related urosepsis.MethodsA retrospective study was carried out in 157 patients with urosepsis after URL. The patients were divided into AKI group and non-AKI group according to the Kidigo guideline and urine IL-8, NGAL and KIM-1 levels were detected by enzyme-linked immunosorbent assay at 0, 4, 12, 24 and 48 h after the surgery. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of these three biomarkers for postoperative AKI.ResultsThe level of urine IL-8, NGAL and KIM-1 in AKI group was significantly higher than that in non-AKI group at 4, 12, 24 and 48 h (p < 0.01). The ROC analysis showed the combined detection of urine IL-8, NGAL and KIM-1 at 12 h had a larger area under curve (AUC) than a single marker (0.997, 95% CI: 0.991–0.998), and the sensitivity and specificity were 98.2% and 96.7%, respectively. Pearson correlation analysis showed that the levels of urine NGAL at 4, 12, 24 and 48 h in AKI patients were positively correlated with the levels of urine KIM-1 and IL-18 (p < 0.01).ConclusionAKI could be quickly recognized by the elevated level of urine IL-8, NGAL and KIM-1 in patients with URL-related urosepsis. Combined detection of the three urine biomarkers at 12 h after surgery had a better diagnostic performance, which may be an important reference for the early diagnosis of AKI.     

Urinary netrin-1 and KIM-1 as early biomarkers for septic acute kidney injury

Background: Acute kidney injury (AKI) during sepsis is associated with poor outcome. However, diagnosis of AKI with serum creatinine (SCr) level change is neither highly sensitive nor specific. Therefore, identification of novel biomarkers for early diagnosis of AKI is desirable. Aims: To evaluate the capacity of combining urinary netrin-1 and human kidney injury molecule type 1 (KIM-1) in the early diagnosis of septic AKI. Methods: We prospectively recruited 150 septic patients from Jun 2011 to Jun 2013 at Zhejiang Provincial People's Hospital, China. SCr, urinary netrin-1, and KIM-1 levels were recorded at 0, 1, 3, 6, 24, and 48?h of ICU admission and compared between AKI and non-AKI patients. In addition, we investigated the prognostic value of netrin-1 and KIM-1 between non-survivors and survivors in septic AKI patients. Results: SCr levels started to show elevation after 24?h of ICU admission. However, netrin-1 levels increased significantly as early as 1?h, peaked at 3–6?h and remained elevated up to 48?h of ICU admission in septic AKI patients. KIM-1 increased significantly by 6?h, peaked at 24?h and remained significantly elevated until 48?h of ICU admission. Furthermore, we observed significant higher urinary KIM-1 levels at 24?h and 48?h in non-survivors compared to survivors in AKI patients. Conclusions: Our results suggest that both netrin-1 and KIM-1 are clinically useful as early biomarkers in the diagnosis of septic AKI. In addition, persistent elevation of urinary KIM-1 level may be associated with poor prognosis.     

Serum and urine acute kidney injury biomarkers in asphyxiated neonates

Background

We evaluated serum (s) cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) and urine (u) CysC, NGAL and kidney injury molecule-1 (KIM-1) as markers of acute kidney injury (AKI) in asphyxiated neonates.

Methods

AKI biomarkers were measured in 13 asphyxiated neonates born at ≥36?weeks gestational age (eight with AKI and five without AKI) and 22 controls. AKI was defined as serum creatinine ≥1.5?mg/dl for >24?h or rising values >0.3?mg/dl from day of life (DOL) 1. Biomarkers were measured on DOL 1, 3, and 10.

Results

Asphyxiated neonates had significantly higher sCysC on DOL 1 as well as sNGAL and uCysC and uNGAL (standardized to urine creatinine and absolute values) than controls at all time points. Compared to controls, significantly higher sNGAL, uCysC, and uNGAL values were observed in the asphyxia-AKI and asphyxia–no AKI subgroups. Regarding uKIM-1, only the absolute values were significantly higher in asphyxiated neonates (DOL 10). sNGAL, uCyst, and uNGAL had a significant diagnostic performance as predictors AKI on DOL 1.

Conclusions

sNGAL, uCysC, and uNGAL are sensitive, early AKI biomarkers, increasing significantly in asphyxiated neonates even in those not fulfilling AKI criteria. Their measurement on DOL 1 is predictive of post-asphyxia-AKI.     

Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review

The diagnosis of acute kidney injury (AKI) is usually based on changes in serum creatinine, but such measurements are a poor marker of acute deterioration in kidney function. We performed a systematic review of publications that evaluated the accuracy and reliability of serum and urinary biomarkers in human subjects when used for the diagnosis of established AKI or early AKI, or to risk stratify patients with AKI. Two reviewers independently searched the MEDLINE and EMBASE databases (January 2000-March 2007) for studies pertaining to biomarkers for AKI. Studies were assessed for methodologic quality. In total, 31 studies evaluated 21 unique serum and urine biomarkers. Twenty-five of the 31 studies were scored as having 'good' quality. The results of the studies indicated that serum cystatin C, urine interleukin-18 (IL-18), and urine kidney injury molecule-1 (KIM-1) performed best for the differential diagnosis of established AKI. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin, IL-18, glutathione-S-transferase-pi, and gamma-glutathione-S-transferase performed best for early diagnosis of AKI. Urine N-acetyl-beta-D-glucosaminidase, KIM-1, and IL-18 performed the best for mortality risk prediction after AKI. In conclusion, published data from studies of serum and urinary biomarkers suggest that biomarkers may have great potential to advance the fields of nephrology and critical care. These biomarkers need validation in larger studies, and the generalizability of biomarkers to different types of AKI as well as the incremental prognostic value over traditional clinical variables needs to be determined.     

Urinary and Serum Biomarkers after Cardiac Catheterization in Diabetic Patients with Stable Angina and without Severe Chronic Kidney Disease

Background/Aims. Different serum and urinary biomarkers have been recently proposed to serve as markers of acute kidney injury. We tested the hypothesis whether NGAL and other biomarkers could represent an early biomarker of contrast nephropathy (CIN) in diabetic patients with normal serum creatinine undergoing cardiac catheterization in comparison with non-diabetic patients. Methods. Serum, urinary NGAL, cystatin C, urinary kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and liver-type fatty acid binding protein (L-FABP) were evaluated before and 2, 4, 8, 24, and 48 hours after cardiac catheterization using commercially available kits. Results. In both groups we found a significant rise in serum NGAL after 2, 4, and 8 hours, and in urinary NGAL and IL-18 after 4, 8, and 24 hours after cardiac catheterization. Serum cystatin C increased significantly 8 hours, reaching peak 24 hours after cardiac catheterization in both groups, and then decreased after 48 hours. L-FABP and KIM-1 increase significantly after 24 and 48 hours after cardiac catheterization. Conclusions. CIN was similarly prevalent in both diabetic and non-diabetic patients undergoing cardiac catheterization. NGAL seems to be a potential early marker for nephrotoxicity and predictor of contrast nephropathy. It is particularly important in the upcoming setting of short-time hospitalizations for cardiac catheterization.     

Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery

Acute kidney injury (AKI) is a frequent complication of cardiopulmonary bypass (CPB). The lack of early biomarkers for AKI has impaired our ability to intervene in a timely manner. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is recently demonstrated as an early biomarker of AKI after CPB, increasing 25-fold within 2 h and declining 6 h after surgery. In the present study, we tested whether interleukin-18 (IL-18) is a predictive biomarker for AKI in the same group of patients following CPB. Exclusion criteria included pre-existing renal insufficiency and nephrotoxin use. Serial urine samples were analyzed by enzyme-linked immunosorbent assay for IL-18 in 20 patients who developed AKI (defined as a 50% or greater increase in serum creatinine after CPB) and 35 controls (age, race, and gender-matched patients who did not develop AKI after CPB). Using serum creatinine, AKI was detected only 48-72 h after CPB. In contrast, urine IL-18 increased at 4-6 h after CPB, peaked at over 25-fold at 12 h, and remained markedly elevated up to 48 h after CPB. The performance of IL-18 as demonstrated by area under the receiver operating characteristics curve for diagnosis of AKI at 4, 12, and 24 h after CPB was 61, 75, and 73% respectively. Also, on multivariate analysis, both IL-18 and NGAL were independently associated with number of days in AKI among cases. Our results indicate that IL-18 is an early, predictive biomarker of AKI after CPB, and that NGAL and IL-18 are increased in tandem after CPB. The combination of these two biomarkers may allow for the reliable early diagnosis and prognosis of AKI at all times after CPB, much before the rise in serum creatinine.     

Value of joint detection of multiple biomarkers on early diagnosis of acute kidney injury in critical patients

Objective To assess the value of joint detection of serum cysteine proteinase inhibitors C (sCys-C), urinary kidney injury molecule 1 (uKIM-1), urinary neutrophil gelatinase-associated lipocalin(uNGAL) and urinary interleukin 18 (uIL-18) for early diagnosis of acute kidney injury (AKI) in critically ill patients. Methods A total of 256 adult patients who stayed Intensive Care Unit for 24 hours in the Third People's Hospital of Liaocheng between Aug 2011 and Dec 2012 were enrolled. According to Kidney Injury Net(AKIN) work, the patients were divided into non-AKI group and AKI group (including state 1, 2 and 3). The concentrations of urine NGAL, KIM-1, IL-18 and serum sCys-C were measured. The diagnosis value of four biomarkers joint detection and single detection for AKI were analyzed with the receiver operating characteristic (ROC) curve and the area under curve (AUC). Results (1) The levels of uNGAL, uKIM-1, uIL-18 and sCys-C were higher in patients with AKI than the patients with no AKI (P﹤0.01). (2) The area under curves of uNGAL, uKIM-1, uIL-18, sCys-C and joint detection were 0.742, 0.871, 0.803, 0.703, 0.925 respectively. (3) The sensitivity and specificity of parallel tests and serial tests of four biomarkers were 97.9%, 62.8%, 64.3% and 96.2% respectively. There were significant differences of sensitivity or specificity between single test and joint tests. Conclusions The urine NGAL, KIM-1, IL-18 and serum Cys-C are sensitive indexes for the early diagnosis of acute kidney injury. Joint detection has high value for early diagnosis of AKI.     

Test characteristics of urinary biomarkers depend on quantitation method in acute kidney injury

The concentration of urine influences the concentration of urinary biomarkers of AKI. Whether normalization to urinary creatinine concentration, as commonly performed to quantitate albuminuria, is the best method to account for variations in urinary biomarker concentration among patients in the intensive care unit is unknown. Here, we compared the diagnostic and prognostic performance of three methods of biomarker quantitation: absolute concentration, biomarker normalized to urinary creatinine concentration, and biomarker excretion rate. We measured urinary concentrations of alkaline phosphatase, γ-glutamyl transpeptidase, cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and IL-18 in 528 patients on admission and after 12 and 24 hours. Absolute concentration best diagnosed AKI on admission, but normalized concentrations best predicted death, dialysis, or subsequent development of AKI. Excretion rate on admission did not diagnose or predict outcomes better than either absolute or normalized concentration. Estimated 24-hour biomarker excretion associated with AKI severity, and for neutrophil gelatinase-associated lipocalin and cystatin C, with poorer survival. In summary, normalization to urinary creatinine concentration improves the prediction of incipient AKI and outcome but provides no advantage in diagnosing established AKI. The ideal method for quantitating biomarkers of urinary AKI depends on the outcome of interest.     

Biomarkers for the early detection of acute kidney injury

Acute kidney injury (AKI), previously referred to as acute renal failure (ARF), represents a persistent problem in clinical medicine. Despite significant improvements in therapeutics, the mortality and morbidity associated with AKI remain high. A major reason for this is the lack of early markers for AKI, akin to troponins in acute myocardial disease, and hence an unacceptable delay in initiating therapy. Fortunately, the application of innovative technologies such as functional genomics and proteomics to human and animal models of AKI has uncovered several novel genes and gene products that are emerging as biomarkers. The most promising of these are chronicled in this article. These include a plasma panel [neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C] and a urine panel [NGAL, interleukin 18 (IL-18), and kidney injury molecule 1 (KIM)-1]. As they represent sequentially expressed biomarkers, it is likely that the AKI panels will be useful for timing the initial insult and assessing the duration of AKI. Based on the differential expression of the biomarkers, it is also likely that the AKI panels will distinguish between the various types and etiologies of AKI. It will be important in future studies to validate the sensitivity and specificity of these biomarker panels in clinical samples from large cohorts and from multiple clinical situations.     

尿生物标志物在儿童急性肾损伤早期诊断中的作用研究

目的：评价尿NGAL,KIM-1和β2-MG在儿童不同基础疾病导致的AKI早期诊断中的价值。方法：我们做的是前瞻性临床研究,检测在我院儿科门急诊不同疾病患儿尿中性粒细胞明胶酶相关的脂质运载蛋白（NGAL）,肾脏损伤因子-1（KIM-1）和-β2微球蛋白（β2-MG）的水平,以AKIpRIFLE为分期标准将入选患儿分组,比较尿NGAL,KIM-1和β2-MG在儿童急性肾损伤诊断中的敏感性,特异性,阳性似然比,阴性似然比,分析比较这3个指标在急性肾损伤早期诊断中的作用。结果：入选262例患儿中,23例患儿可诊断为AKI,15例患儿为AKI-R期,8例患儿为AKI-I期,入选患儿中没有AKI-F期,23例患儿中只有5例临床有AKI的诊断。尿NGAL,KIM-1和β2-MG的水平在血肌酐没有明显升高之前已经升高,随着肾损伤的加重升高的更明显,不同组间差异有统计学意义。尿NGAL和β2-MG在预测儿童AKI的早期诊断方面好于尿KIM-1（AUC〉0.8）。结论：尿NGAL,KIM-1和β2-MG均可以在Scr没有升高之前预测儿童AKI的发生,是儿童AKI的早期生物标志物。尿NGAL在早期预测不同基础疾病可能发生AKI方面好于其他两项指标。     

肝移植术后急性肾损伤的早期诊断

背景 急性肾损伤(acute kidney injury,AKI)为肝移植术后常见严重并发症,其发生威胁患者生存.文献报道AKI发生率差异较大,原因可能与不同研究中AKI的诊断标准不一致有关. 目的 探讨肝移植术后AKI早期诊断的最新进展,以便积极预防、尽早治疗. 内容 综述肝移植术后AKI的常用诊断标准及其发生的相关危险因素,并讨论可能的诊断新指标. 趋向 血肌酐(serum creatinine,Scr)是目前诊断AKI最常用的生物标志物,但近年来研究指出,中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)、肾损伤分子-1(kidney injury molecule-1,KIM-1)、胱抑素C(Cystatin C,Cys-C)等新型生物学标志物或许可替代Scr,成为早期诊断AKI的理想指标.     

Value of levels of biomarkers at the time of nephrologists consultation in predicting the prognosis of acute kidney injury patients

Objective To investigate the value of biomarker levels at the time of nephrologists consultation in predicting the prognosis of acute kidney injury (AKI) patients. Methods A total of 103 hospitalized patients with AKI were enrolled at the time of nephrologists consultation. Blood and urine samples were collected when patients were diagnosed as AKI. ELISA was used to detect the concentration of urinary biomarkers including neutrophil gelatinase?associated lipocalin (NGAL), IL?6 and IL?18. Colorimetric method was used to measure urinary N?acetyl?β?D?glucosaminidase (NAG). Turbidimetry and enzymic method were applied to examine the concentration of serum cystatin C (Cys C), baseline Scr (bScr), Scr at consultation (cScr) and the peak of Scr (pScr) respectively. Patients were followed?up to evaluate the prognosis at 28 days after consultation, including patient survival and kidney survival. The levels of biomarkers between different groups, including patient survival or death, kidney recovery or lose and renal replacement therapy (RRT) or not, were compared. Area under curve (AUC) of receiver operating characteristic (ROC) curve of these biomarkers were used to evaluate the sensitivity and specificity in predicting prognosis. AKI was defined as the Scr at the time of consultation increased more than 50% of baseline Scr within 48 hours. Results (1)Mean age of 103 hospitalized AKI patients was (54.28±19.05) years old and ratio of male to female was 1.86 to 1. (2)Patient mortality was 25.2% at 28 days after consultation. The bScr, cScr and pScr were similar between survival and death group, while the concentration of urinary NGAL in death group was significantly higher than that of survival group [147.00(31.59, 221.87) mg/L vs 22.43(6.48, 89.77) mg/L, P＝0.001]. The serum Cys C, urinary IL?6 and NAG were similar between survival and death group (P＞0.05). Logistic regression analysis showed urinary NGAL was an independent risk factor of patient survival (OR＝1.011, 95%CI 1.004?1.018, P＝0.001) with AUC of 0.723. (3)Kidney lose rate was 20.4% at 28 days after consultation. The bScr, cScr and pScr were similar between patients with kidney survival and lose. The levels of urinary NAG, IL?6, NGAL and IL?18 were significantly higher in patients with kidney lose than those of kidney survival. Logistic regression analysis showed urinary IL?6 was an independent risk factor of renal survival (OR＝1.056, 95%CI 1.009?1.105, P＝0.018) with AUC of 0.705. (4)The median time from consultation to RRT was 2.17 (0?3) days. The concentrations of cScr, pScr, serum Cys C, urinary IL?6 and NGAL were significantly higher in RRT patients than thosein non?RRT patients (P＜0.05). Logistic regression analysis showed urinary NGAL was an independent risk factor of RRT (OR＝1.012, 95%CI 1.005?1.019, P＜0.01) with AUC of 0.775. Conclusions Urinary NGAL can predict the prognosis of AKI patients, including patient prognosis and RRT. Urinary IL?6 may predict kidney prognosis in hospitalized patients with AKI. More study with large samples should be done for further estimation of the results.     

Urinary markers of acute kidney injury in newborns with perinatal asphyxia*

Background: Acute kidney injury (AKI) affects up to 60% of severely asphyxiated neonates. The diagnosis of AKI can be and is further challenged by a lack of good biomarkers. We studied the role of novel markers for AKI, neutrophil gelatinase-associated lipocalin (NGAL), interleukin-8 (IL-18), Netrin-1 (NTN-1), and sodium hydrogen exchanger isoform 3 (NHE3) on development and early diagnosis of AKI in newborns with perinatal asphyxia (PA). Methods: Forty-one newborns with a diagnosis of PA (15 with AKI and 26 without AKI) and 20 healthy matched controls were involved to the study. Urinary samples were obtained on postnatal days 1 and 4 for patients with PA and on postnatal day 1 for the control subjects. AKI was defined using a serum creatinine-based modification of the acute kidney injury network criteria. Results: The levels of NGAL, NTN-1, NHE3, and IL-18 on the first postnatal day urine samples were higher in patients compared to controls (p?<?0.001, p?<0.001, p <0.02, p <0.001, respectively). In patients with AKI, the levels of NGAL and IL-18 were higher when compared to patients without AKI (p?=?0.002, p <0.001, respectively). The levels of NTN-1 and NHE3 were similar in both groups. For the samples obtained on postnatal day 4, only NGAL levels were significantly higher in patients with AKI (p?=?0.004) compared to those without AKI. Conclusion: To our knowledge, this is the largest study, which evaluated the utility of urinary biomarkers in the diagnosis of AKI in newborns with PA. First day, urine NGAL and IL-18 levels have an important diagnostic power in such patients.     

尿NGAL、NAG及KIM-1联合检测在高龄老年急性肾损伤早期诊断中的价值

目的探讨尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)、尿N-乙酰β-D氨基葡萄糖苷酶(uNAG)及尿肾损伤分子-1(uKIM-1)的联合检测老年急性肾损伤中的诊断价值。方法选择2016年6月至2018年6月在泰山疗养院住院的老年患者184例,根据急性肾损伤网络(AKIN)标准为诊断标准,诊断AKI组116例(1期55例、2期39例、3期24例),非AKI组68例,检测并比较各组尿NGAL、NAG、KIM-1水平,用受试者工作特征曲线(ROC)及曲线下面积(AUC)分析3项生物学标志物对AIK的诊断价值。结果①AKI组尿NGAL、NAG、KIM-1明显高于对照组(P<0.05),3期尿NGAL、NAG、KIM-1明显高于2期和1期,2期明显高于1期(P<0.05);②尿NGAL、NAG、KIM-1单独诊断AKI的AUC分别为0.734、0.804、0.705;③3项标志物联合诊断AKI的灵敏度、特异度分别为84.9%、90.7%,高于各单项诊断。结论尿NGAL、NAG、KIM-1是诊断AKI的较好指标,联合诊断对高龄老年急性肾损伤的早期诊断有着更重要的价值。     

心脏术后尿中性粒细胞明胶酶相关脂质运载蛋白和白细胞介素18与急性肾损伤的关系

目的 探讨接受体外循环心脏手术患者尿中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和尿白细胞介素18（IL-18）与急性肾损伤（AKI）的关系。 方法 根据AKI的诊断标准，将33例体外循环心脏手术的患者分为AKI组及非AKI组，分别留取术前及术后不同时间点的血液和尿液标本，测定Scr、尿NGAL和IL-18水平。 结果 33例中有9例发生AKI，发生率为27.27%。AKI组Scr升高峰值出现在12～48 h内。与术前相比， AKI组术后2 h、4 h尿NGAL及IL-18水平升高，差异有统计学意义（P < 0.01）。与非AKI组比较，AKI组术后各时间点的尿NGAL水平、术后2 h及4 h的尿IL-18水平都较高，差异有统计学意义（P < 0.01）。经尿肌酐（Ucr）校正后，相应时间点的NGAL/Ucr和IL-18/Ucr差异仍有统计学意义（P < 0.01）。术后2 h尿NGAL和尿NGAL/Ucr的界定（cutoff） 值分别在250 µg/L和250 µg/mmol时；术后2 h尿IL-18和尿IL-18/Ucr的界定值分别在1800 ng/L和1800 ng/mmol时，体现出较好的敏感性和特异性。 AKI组术后12 h Scr水平与术后2 h尿NGAL水平呈正相关（r = 0.638，P < 0.05）。结论 体外循环下接受心脏手术的患者AKI发生率较高；术后2 h尿NGAL和NGAL/Ucr、术后2 h尿IL-18和尿IL-18/Ucr当达到一定界定值时，均可作为体外循环下心脏手术后AKI发生的早期诊断参考指标，其中术后2 h尿NGAL/Ucr为250 µg/mmol时更敏感。     

Postoperative biomarkers predict acute kidney injury and poor outcomes after pediatric cardiac surgery

Acute kidney injury (AKI) occurs commonly after pediatric cardiac surgery and associates with poor outcomes. Biomarkers may help the prediction or early identification of AKI, potentially increasing opportunities for therapeutic interventions. Here, we conducted a prospective, multicenter cohort study involving 311 children undergoing surgery for congenital cardiac lesions to evaluate whether early postoperative measures of urine IL-18, urine neutrophil gelatinase-associated lipocalin (NGAL), or plasma NGAL could identify which patients would develop AKI and other adverse outcomes. Urine IL-18 and urine and plasma NGAL levels peaked within 6 hours after surgery. Severe AKI, defined by dialysis or doubling in serum creatinine during hospital stay, occurred in 53 participants at a median of 2 days after surgery. The first postoperative urine IL-18 and urine NGAL levels strongly associated with severe AKI. After multivariable adjustment, the highest quintiles of urine IL-18 and urine NGAL associated with 6.9- and 4.1-fold higher odds of AKI, respectively, compared with the lowest quintiles. Elevated urine IL-18 and urine NGAL levels associated with longer hospital stay, longer intensive care unit stay, and duration of mechanical ventilation. The accuracy of urine IL-18 and urine NGAL for diagnosis of severe AKI was moderate, with areas under the curve of 0.72 and 0.71, respectively. The addition of these urine biomarkers improved risk prediction over clinical models alone as measured by net reclassification improvement and integrated discrimination improvement. In conclusion, urine IL-18 and urine NGAL, but not plasma NGAL, associate with subsequent AKI and poor outcomes among children undergoing cardiac surgery.     

Prognostic value of urinary kidney injury molecule 1, interleukin 18 and cystatin C as biomarkers for gadolinium-based contrast-induced nephropathy in the elderly patients

Objective To assess the prognostic values of urinary kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18) and cystatin C (Cys C) for gadolinium-based contrast-induced nephropathy (Gd-CIN) in the elderly patients. Methods A total of sixty elderly patients who underwent enhanced magnetic resonance imaging (MRI) using gadolinium-based contrast media (GBC) from December 2010 to December 2011 were enrolled. Serum and urine samples were collected before and after the procedure. The levels of urinary KIM-1, IL-18 and Cys C were measured by ELISA respectively. Serum and urine creatinine levels were measured by automatic biochemical analyzer. Results Among 60 patients, Gd-CIN was diagnosed in 8 (13.3%) patients. At 24 h after MRI in the Gd-CIN group, the levels of urinary KIM-1, IL-18 and Cys C were significantly increased compared with the baseline values. Compared with non-Gd-CIN group, the levels of urinary KIM-1, IL-18 and Cys C at 24 h and urinary IL-18 at 48 h after GBC administration were significantly increased (P＜0.05). There were no significant differences in levels of urinary KIM-1, Cys C at 48 h after GBC administration between Gd-CIN and non-Gd-CIN group (P＞0.05). Logistic regression analysis showed that the levels of urinary KIM-1 and IL-18 at 24 h after GBC injection were independent predictive biomarkers of Gd-CIN (OR＝1.612, 1.009, all P＜0.05). The predictable time of acute kidney injury onset determined by urinary KIM-1, IL-18 and Cys C levels was 24 h earlier than that by serum creatinine. Conclusion Urinary KIM-1, IL-18 and Cys C may be early predictive biomarkers of elderly Gd-CIN, which shows a good performance in early diagnosis of Gd-CIN as compared with serum creatinine.     

Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass

Abstract

Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary α and π glutathione S-transferases (α-GST and π-GST), urinary l-type fatty acid-binding protein (l-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24?h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. π-GST (ROCAUC?=?0.75), lower urine Hepcidin:Creatine ratio at 24?h (0.77), greater urine NGAL:Cr ratio post-op (0.73) and greater serum CysC at 24?h (0.72) best predicted AKI. Linear combinations with significant improvement in AUC were: Hepcidin:Cr 24?h?+?post-operative π-GST (AUC?=?0.86, p?=?0.01), Hepcidin:Cr 24?h?+?NGAL:Cr post-op (0.84, p?=?0.03) and CysC 24?h?+?post-operative π-GST (0.83, p?=?0.03), notably these significant biomarkers combinations all involved a tubular injury and a glomerular filtration biomarker. Despite statistical significance in receiver–operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24?h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.     

Neutrophil gelatinase-associated lipocalin: a novel biomarker in acute kidney injury

Acute kidney injury (AKI) is a frequent complication in critically ill patients and is associated with high morbidity and mortality; therefore, its prophylaxis, diagnosis and intervention positively impact patient evolution. Neutrophil gelatinase-associated lipocalin (NGAL) or lipocalin, a protein synthesized by renal tubular cells, has the property to transport lipophilic molecules such as vitamins, hormones and antigenic agents. It is a novel biomarker of AKI of several etiologies and is increased in both serum and urine 48 h before the increase of creatinine. It has a strong correlation with early diagnosis of AKI. NGAL is of the most investigated and promising biomarkers for early diagnosis of AKI in different clinical scenarios, most notably in sepsis, cardiorenal syndrome, cardiac surgery, kidney transplant, contrast nephropathy and hemolytic uremic syndrome. Lipocalin guides the early institution of therapeutic interventions to improve prognosis in AKI of several etiologies.