Some biomarkers of acute kidney injury are increased in pre-renal acute injury

Pre-renal acute kidney injury (AKI) is assumed to represent a physiological response to underperfusion. Its diagnosis is retrospective after a transient rise in plasma creatinine, usually associated with evidence of altered tubular transport, particularly that of sodium. In order to test whether pre-renal AKI is reversible because injury is less severe than that of sustained AKI, we measured urinary biomarkers of injury (cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), γ-glutamyl transpeptidase, IL-18, and kidney injury molecule-1 (KIM-1)) at 0, 12, and 24?h following ICU admission. A total of 529 patients were stratified into groups having no AKI, AKI with recovery by 24?h, recovery by 48?h, or the composite of AKI greater than 48?h or dialysis. Pre-renal AKI was identified in 61 patients as acute injury with recovery within 48?h and a fractional sodium excretion <1%. Biomarker concentrations significantly and progressively increased with the duration of AKI. After restricting the AKI recovery within the 48?h cohort to pre-renal AKI, this increase remained significant. The median concentration of KIM-1, cystatin C, and IL-18 were significantly greater in pre-renal AKI compared with no-AKI, while NGAL and γ-glutamyl transpeptidase concentrations were not significant. The median concentration of at least one biomarker was increased in all but three patients with pre-renal AKI. Thus, the reason why some but not all biomarkers were increased requires further study. The results suggest that pre-renal AKI represents a milder form of injury.     

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.     

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。     

尿中性粒细胞明胶酶相关脂质运载蛋白在成人心脏手术后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（neutrophil gelatinase-associated lipocalin,NGAL）在心脏手术后急性肾损伤（AKI）早期预测和诊断中的价值。 方法 前瞻性收集我院心脏手术患者手术前后不同时相的血、尿标本,选取其中14例AKI患者,分别测定尿NGAL和Scr水平;并选择临床资料相匹配的非AKI患者15例作为对照。观察两组患者围手术期尿NGAL和Scr的动态变化,运用接受者操作特性曲线（ROC）评价尿NGAL诊断AKI的精确性。AKI定义为Scr水平较基础值增加≥50%。 结果 Scr诊断AKI的中位时间为入ICU后24 h（10 h,48 h）。AKI患者术后入ICU即刻的尿NGAL水平显著高于术前基础水平并达峰值[20.51（13.42,50.02） μg/L比3.42（1.60,9.92） μg/L,P = 0.006];也显著高于非AKI患者 [2.91（0.72,8.61） μg/L,P = 0.002]。入ICU即刻尿NGAL 的ROC曲线下面积为0.824,95%的可信区间（CI）为0.667~0.980,P = 0.003。当以10.95 μg/L作为诊断截点时,此刻的尿NGAL在AKI诊断中的敏感性和特异性分别为85.7%和80.0%。入ICU即刻的尿NGAL与入ICU 24 h的Scr（r = 0.545,P = 0.002）及eGFR（r = －0.546,P = 0.002)呈正及负相关。 结论 心脏手术后AKI患者术后入ICU即刻的尿NGAL水平显著升高,对诊断AKI具有较高的准确性,其诊断AKI的时间早于Scr。尿NGAL可作为成人心脏术后AKI的早期诊断标志物。     

Septic acute kidney injury in critically ill patients – a single-center study on its incidence,clinical characteristics,and outcome predictors

Purpose The objective of this study is to examine the incidence, clinical characteristics, and outcome (90-day mortality) of critically ill Chinese patients with septic AKI. Methods Patients admitted to the ICU of a regional hospital from 1 January 2011 to 31 December 2013 were included, excluding those on chronic renal replacement therapy. AKI was defined using KDIGO criteria. Patients were followed till 90 days from ICU admission or death, whichever occurred earlier. Demographics, diagnosis, clinical characteristics, and outcome were analyzed. Results In total, 3687 patients were included and 54.7% patients developed AKI. Sepsis was the most common cause of AKI (49.2%). Compared to those without AKI, AKI patients had higher disease severity, more physiological and biochemical disturbance, and carried significant co-morbidities. Ninety-day mortality increased with severity of AKI (16.7, 27.5, and 48.3% for KDIGO stage 1, 2, and 3 AKI, p?<?0.001). Full renal recovery was achieved in 71.6% of AKI patients. Compared with non-septic AKI, septic AKI was associated with higher disease severity and required more aggressive support. Non-recovery of renal function occurred in 2.5% of patients with septic AKI, compared with 6.4% in non-septic AKI (p?<?0.001). Cox regression analysis showed that age, emergency ICU admission, post-operative cases, admission diagnosis, etiology of AKI, disease severity score, mechanical ventilation, vasopressor support, and blood parameters (like albumin, potassium and pH) independently predicted 90-day mortality. Conclusions AKI, especially septic AKI is common in critically ill Chinese patients and is associated with poor patient outcome. Etiology of AKI has a significant impact on 90-day mortality and may affect renal outcome.     

Le dosage plasmatique de Neutrophil Gelatinase-Associated Lipocalin (NGAL) prédit la défaillance rénale au cours du choc septique dès l’admission en réanimation

Purpose

To validate plasma Neutrophil Gelatinase-Associated Lipocalin (pNGAL) as an early biomarker in intensive care unit (ICU) for acute kidney injury (AKI) in critically ill adult with septic shock.

Patients and method

Fifty consecutive patients with septic shock were included in this observational cohort study. AKI was defined if patients met any RIFLE or AKIN criteria. The main objective was to evaluate diagnosis value of pNGAL measured with a point-of-care device at admission (D0), at 24 hours (D1) and at 48 hours (D2).

Results

Among the 50 patients enrolled, 86% had AKI, 48% had persistent renal AKI and 30% required renal replacement therapy (RRT) during their ICU stay. At D0, pNGAL concentration was significantly higher in patients with AKI compared to patients without AKI (471 ng/mL versus 134 ng/mL, P < 0.001). This level remained significantly higher in the AKI population at D1 and D2 and pNGAL concentration at D0 among AKI patients increased with kidney failure level. At D1, pNGAL was significantly higher for persistent renal AKI rather than transient prerenal (570 ng/mL versus 337 ng/mL, P = 0.027). pNGAL concentration below 348 ng/mL at D1 was never seen in patients with RRT.

Conclusion

Plasma NGAL is a useful, sensitive and early biomarker to predict persistent AKI in septic shock at ICU admission and help to discuss RRT.     

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.     

A combination of SOFA score and biomarkers gives a better prediction of septic AKI and in-hospital mortality in critically ill surgical patients: a pilot study

Background

Sepsis is a syndrome characterized by a constellation of clinical manifestations and a significantly high mortality rate in the surgical intensive care unit (ICU). It is frequently complicated by acute kidney injury (AKI), which, in turn, increases the risk of mortality. Therefore, it is of paramount importance to identify those septic patients at risk for the development of AKI and mortality. The objective of this pilot study was to evaluate several different biomarkers, including NGAL, calprotectin, KIM-1, cystatin C, and GDF-15, along with SOFA scores, in predicting the development of septic AKI and associated in-hospital mortality in critically ill surgical patients.

Methods

Patients admitted to the surgical ICU were prospectively enrolled, having given signed informed consent. Their blood and urine samples were obtained and subjected to enzyme-linked immunosorbent assay (ELISA) to determine the levels of various novel biomarkers. The clinical data and survival outcome were recorded and analyzed.

Results

A total of 33 patients were enrolled in the study. Most patients received surgery prior to ICU admission, with abdominal surgery being the most common type of procedure (27 patients (81.8%)). In the study, 22 patients had a diagnosis of sepsis with varying degrees of AKI, while the remaining 11 were free of sepsis. Statistical analysis demonstrated that in patients with septic AKI versus those without, the following were significantly higher: serum NGAL (447.5?±?35.7 ng/mL vs. 256.5?±?31.8 ng/mL, P value 0.001), calprotectin (1030.3?±?298.6 pg/mL vs. 248.1?±?210.7 pg/mL, P value 0.049), urinary NGAL (434.2?±?31.5 ng/mL vs. 208.3?±?39.5 ng/mL, P value <?0.001), and SOFA score (11.5?±?1.2 vs. 4.4?±?0.5, P value <?0.001). On the other hand, serum NGAL (428.2?±?32.3 ng/mL vs. 300.4?±?44.3 ng/mL, P value 0.029) and urinary NGAL (422.3?±?33.7 ng/mL vs. 230.8?±?42.2 ng/mL, P value 0.001), together with SOFA scores (10.6?±?1.4 vs. 5.6?±?0.8, P value 0.003), were statistically higher in cases of in-hospital mortality. A combination of serum NGAL, urinary NGAL, and SOFA scores could predict in-hospital mortality with an AUROC of 0.911.

Conclusions

This pilot study demonstrated a promising panel that allows an early diagnosis, high sensitivity, and specificity and a prognostic value for septic AKI and in-hospital mortality in surgical ICU. Further study is warranted to validate our findings.

     

尿肾损伤分子1与白细胞介素18对急性肾损伤患者的诊断价值

目的：观察尿肾损伤分子1（kidney inj ury molecule-1,Kim-1）与白细胞介素18（inter-leukin-18,IL-18）在急性肾损伤（acute kidney injury,AKI）患者中的变化,探讨其对 AKI的诊断价值。方法选择我院确诊为AKI患者71例（AKI组）,并根据AKI分期,分为AKI 1期组23例、AKI 2期组25例和 AKI 3期组23例;另选择同时期我院体检中心健康体检者30名（健康对照组）,分别检测2组患者尿Kim-1、尿 IL-18及血肌酐（SCr）水平。结果 AKI组 SCr、尿Kim-1较健康对照组明显升高（P〈0.01）,尿 IL-18亦升高（P〈0.05）,与健康对照组比较,SCr、尿 Kim-1在 AKI 1期组、AKI 2期组、AKI 3期组均明显升高（P〈0.01）,尿 IL-18在 AKI 2期组、AKI 3期组亦明显升高（P〈0.01）,在 AKI 1期组虽升高,但差异无统计学意义（P〉0.05）;与 AKI 1期组比较,SCr、尿 Kim-1在 AKI 2期组、AKI 3期组均明显升高（P〈0.01）,尿IL-18在AKI 2期升高（P〈0.05）,在AKI 3期组亦升高（P〈0.01）,与 AKI 2期组比较,SCr、尿 Kim-1及尿 IL-18在 AKI 3期组均明显升高（P〈0.01）;而且相关性分析显示,尿 Kim-1与 SCr 呈正相关（r=0.842,P〈0.01）;尿 IL-18与 SCr 呈正相关（r=0.785,P〈0.01）;尿Kim-1与尿 IL-18呈正相关（r=0.756,P〈0.01）。而 ROC 曲线下面积比较结果显示,尿Kim-1（0.915）明显大于尿 IL-18（0.807）（P〈0.05）。结论尿 Kim-1、尿 IL-18在 AKI患者中升高,二者均可能作为 AKI的诊断标准,且尿Kim-1诊断价值可能更高。     

Value of kidney injury molecule -1 in the diagnosis of acute kidney injury: a Meta analysis

Objective To access the early diagnosis value of kidney injury molecule-1 (KIM-1) in patients with acute kidney injury (AKI) by Meta-analysis. Methods Databases MEDLINE, EMBASE, Pubmed, Elsevier Science Direct, Scopus, Web of Science, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and WanFang Data were retrieved to collect the diagnostic tests on KIM-1 for AKI published before July 2013. The literatures were screened independently by two reviewers according to the inclusion and exclusion criteria, the data were extracted, and the methodological quality was assessed. Statistic software Meta-Disc 1.4 and STATA 12.0 were used to conduct analyses. Results Eighteen articles were included in this study with a total of 3 427 patients. The summary for urinary KIM-1 in the diagnosis of AKI were sensitivity 0.67(95%CI: 0.63, 0.70), specificity 0.80 (95%CI: 0.78, 0.81), positive likelihood ratio 3.53(95%CI：2.73, 4.56), negative likelihood ratio 0.30 (95%CI: 0.21, 0.42), diagnostic odds ratio 15.13(95%CI: 8.40, 27.25), and the area under the curve (AUC) of summary receiver operating characteristic curves (SROC) was 0.865 2. Subgroup analysis revealed the sensitivity, specificity and diagnostic odds ratio of urinary KIM-1 measured after 2 to12 h post operation in diagnosis of AKI after cardiac surgery were 0.88(95%CI: 0.81, 0.93), 0.75(95%CI: 0.71, 0.79) and 30.22 (95%CI: 16.19, 56.42), respectively. The AUC of SROC was 0.923 7. Conclusions KIM-1 as a single indicator has moderate accuracy for early diagnosing AKI, especially with a high diagnostic accuracy in AKI after cardiac surgery.     

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。     

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.     

KIM-1、CC16在急性肾/肺损伤临床诊断中的意义

目的观察肾损伤分子-1（kidney injury molecule 1, KIM-1）与Clara细胞分泌蛋白（Clara cell secretion protein, CCSP/CC16）在急性肾损伤（Acute Kidney Injury, AKI）合并急性肺损伤（Acute Lung Injury, ALI）患者体内的变化,探讨其在急性肾/肺损伤临床诊断中的意义。方法入选本院确诊为AKI的患者纳入AKI组（25例）,确诊为ALI的患者纳入ALI组（15例）,确诊为AKI合并ALI的患者纳入AKI+ALI组（25例）,与之年龄、性别、民族相匹配的非吸烟健康志愿者作为正常对照组（23例）,采用酶联免疫吸附法(enzyme-linked immunosorbent assay, ELISA)检测尿液KIM-1、尿液CC16和血浆KIM-1、血浆CC16的水平,用比色法检测尿N-乙酰-β-D-氨基葡萄糖苷酶(N-acetyl-beta-D-glucosaminidase, NAG),整理四组所有研究资料利用统计学方法进行综合分析。 结果与正常非吸烟对照组相比,AKI组的尿NAG酶、尿KIM-1、血浆KIM-1和血浆CC16水平均显著升高,差异有统计学意义（P＜0.05）;ALI组的尿CC16和血浆CC16水平均显著升高,差异有统计学意义（P＜0.05）;AKI+ALI组的尿NAG酶、尿KIM-1、血浆KIM-1、尿CC16和血浆CC16水平均显著升高,差异有统计学意义（P＜0.05）。 直线相关分析显示：AKI患者的尿KIM-1水平与尿NAG呈显著正相关关系（r=0.493, P＜0.01）,血浆KIM-1水平与尿NAG无直线相关关系（r=0.276, P＞0.05）。ALI患者的尿CC16、血浆CC16与氧合指数均呈显著负相关关系(r=0.460, P＜0.01; r=0.468, P＜0.01)。AKI合并ALI患者的尿KIM-1、血浆KIM-1与尿CC16、血浆CC16均呈显著正相关关系（P＜0.05）。3. ROC曲线分析提示：在AKI诊断中,尿KIM-1曲线下面积为0.781（95% CI：0.688～0.875,P＜0.01）;血浆KIM-1曲线下面积为0.988（95% CI：0.000～1.000,P＜0.01）;尿NAG酶曲线下面积为0.798（95% CI：0.708～0.888,P＜0.01）。在ALI诊断中,尿CC16曲线下面积为1.000(95% CI：1.000～1.000,P＜0.01);血浆CC16曲线面积为0.849（95% CI：0.764～0.935,P＜0.01）。 结论 AKI时尿NAG、尿KIM-1、血浆KIM-1均明显升高,进一步证实这些指标可作为诊断AKI早期生物学标志物。2. ALI时尿CC16、血浆CC16水平显著升高,同时具有高敏感性,是诊断ALI的良好实验室指标。急性肾/肺损伤患者体内尿、血浆KIM-1与CC16水平明显升高,二者具有良好的相关性,对诊断急性肾/肺损伤并判断预后具有重要的价值与临床意义。     

Prediction of acute kidney injury complicated by sepsis with sTREM - 1 and NGAL as early marker

Objective To determine whether triggering receptor expressed on myeloid cells-1 (sTREM - 1) and urinary neutrophil gelatinase - associated lipocalin (NGAL) were early biomarkers of acute kidney injury (AKI) secondary to sepsis. Methods A total of 141 eligible patients were enrolled in this prospective study. Blood and urine samples were collected at different time points as soon as sepsis was diagnosed. The concentrations of serum creatinine (Scr), urine sTREM-1 and NGAL were measured. According to AKI criteria, patients were divided into the AKI group and non - AKI group. Dynamic changes of levels of Scr, urine sTREM-1 and NGAL were observed in two groups. The receiver operating characteristic curves were used to evaluate the early diagnostic value of urine sTREM-1 and NGAL. Results Among 141 septic patients, 44 (31.2%) cases had concomitant AKI. Twenty four hours after sepsis diagnosed, the level of Scr rose to 1.91 times of the baseline [(140.5±13.6) vs (82.6±15.3) μmol/L, P＜0.05], which met the diagnostic criteria of AKI. In the AKI group, urinary concentrations of sTREM-1 and NGAL at 8 h after the diagnosis of sepsis began to rise significantly from baseline [(100.5±17.4) vs (38.9±14.7) ng/L; (144.6±51.9) vs (56.2±43.8) μg/L, both P＜0.05].And at the following time points, urinary concentrations of sTREM - 1 and NGAL were significantly higher than the baseline levels and that of the non-AKI group (all P＜0.05). At 8 h time point, the area under the curve of urine sTREM-1 was 0.877 (95%CI 0.756-0.914), the sensitivity was 89.1% and specificity was 82.0% with a cutoff value of 70 ng/L. At 8 h time point, the area under the curve of urine NGAL was 0.862 (95% CI 0.703-0.958),the sensitivity was 87.4% and specificity was 85.5% with a cutoff value of 90 μg/L. Conclusions Urinary concentrations of sTREM-1 and NGAL at 8 h time point after the diagnosis of sepsis have predictive value for AKI and their diagnostic time is much earlier than that of Scr. Therefore, urinary sTREM-1 and NGAL can be used as early biomarkers of septic AKI.     

Urinary biomarkers to detect acute kidney injury in the pediatric emergency center

We conducted a prospective study in pediatric patients presenting to an emergency center (EC) to (1) test the ability of urinary acute kidney injury (AKI) biomarkers to predict AKI presence and severity and (2) determine if these biomarkers offer similar precision in patients with versus without a known baseline SCr. The accuracy of five putative urinary biomarkers to detect AKI presence and severity was evaluated in 252 children presenting to our EC. AKI was defined by the modified pediatric RIFLE (pRIFLE) system. Eighteen children had AKI by pRIFLE, yet 33–50% of these AKI cases may have been missed since the EC SCr was <1 mg/dl. Urinary NGAL, Kidney Injury Molecule-1 (KIM-1) and beta-2 microglobulin (β2M) all demonstrated good to very good accuracy (AUC > 0.70 to 0.80) to predict patients with pRIFLE-Injury (>50% decrease in eCCl) versus patients with pRIFLE-Risk (25–50% decrease in eCCl) or without AKI. Our data suggest urinary biomarkers may serve well to detect AKI accurately in the pediatric EC setting, even in cases where SCr levels are normal. Further study is required to determine if these biomarkers obtained in the EC can predict AKI development or progression in hospitalized patients.     

Blood Kidney Injury Molecule-1 Is a Biomarker of Acute and Chronic Kidney Injury and Predicts Progression to ESRD in Type I Diabetes

Currently, no blood biomarker that specifically indicates injury to the proximal tubule of the kidney has been identified. Kidney injury molecule-1 (KIM-1) is highly upregulated in proximal tubular cells following kidney injury. The ectodomain of KIM-1 is shed into the lumen, and serves as a urinary biomarker of kidney injury. We report that shed KIM-1 also serves as a blood biomarker of kidney injury. Sensitive assays to measure plasma and serum KIM-1 in mice, rats, and humans were developed and validated in the current study. Plasma KIM-1 levels increased with increasing periods of ischemia (10, 20, or 30 minutes) in mice, as early as 3 hours after reperfusion; after unilateral ureteral obstruction (day 7) in mice; and after gentamicin treatment (50 or 200 mg/kg for 10 days) in rats. In humans, plasma KIM-1 levels were higher in patients with AKI than in healthy controls or post-cardiac surgery patients without AKI (area under the curve, 0.96). In patients undergoing cardiopulmonary bypass, plasma KIM-1 levels increased within 2 days after surgery only in patients who developed AKI (P<0.01). Blood KIM-1 levels were also elevated in patients with CKD of varous etiologies. In a cohort of patients with type 1 diabetes and proteinuria, serum KIM-1 level at baseline strongly predicted rate of eGFR loss and risk of ESRD during 5–15 years of follow-up, after adjustment for baseline urinary albumin-to-creatinine ratio, eGFR, and Hb1Ac. These results identify KIM-1 as a blood biomarker that specifically reflects acute and chronic kidney injury.     

Netrin-1: A Novel Universal Biomarker of Human Kidney Injury

Currently available diagnostic markers representing kidney injury or function such as serum creatinine and blood urea nitrogen are insensitive and often increased late in the disease process. Netrin-1 protein, a laminin-related secreted molecule, is minimally or not expressed in tubular epithelial cells of normal kidneys. However, it is highly expressed in injured kidneys. Netrin-1 protein has been shown to be detected in urine from mice with acute kidney injury. The current study was carried out to evaluate whether netrin-1 is also induced in human acute kidney injury (AKI) and can serve as a urinary biomarker of the condition. We analyzed netrin-1 levels by sandwich enzyme-linked immunosorbent assay in urine samples from 10 healthy controls, 22 recipients of a renal allograft, 11 patients with ischemic AKI, 13 with AKI associated with sepsis, 9 with radiocontrast-induced AKI, and 8 with drug-induced AKI. Urinary netrin-1 levels normalized for urinary creatinine were significantly higher in all subject groups. The highest values were observed in patients with sepsis and in transplant patients immediately postoperatively. The level of NGAL was similarly increased in transplant patients. In conclusion, urinary netrin-1 levels are increased in patients with various forms of AKI/ATN and may serve as a universal biomarker for AKI.     

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.     

Predicting renal function recovery and short-term reversibility among acute kidney injury patients in the ICU: comparison of machine learning methods and conventional regression

BackgroundAcute kidney injury (AKI) is one of the most frequent complications of critical illness. We aimed to explore the predictors of renal function recovery and the short-term reversibility after AKI by comparing logistic regression with four machine learning models.MethodsWe reviewed patients who were diagnosed with AKI in the MIMIC-IV database between 2008 and 2019. Recovery from AKI within 72 h of the initiating event was typically recognized as the short-term reversal of AKI. Conventional logistic regression and four different machine algorithms (XGBoost algorithm model, Bayesian networks [BNs], random forest [RF] model, and support vector machine [SVM] model) were used to develop and validate prediction models. The performance measures were compared through the area under the receiver operating characteristic curve (AU-ROC), calibration curves, and 10-fold cross-validation.ResultsA total of 12,321 critically ill adult AKI patients were included in our analysis cohort. The renal function recovery rate after AKI was 67.9%. The maximum and minimum serum creatinine (SCr) within 24 h of AKI diagnosis, the minimum SCr within 24 and 12 h, and antibiotics usage duration were independently associated with renal function recovery after AKI. Among the 8364 recovered patients, the maximum SCr within 24 h of AKI diagnosis, the minimum Glasgow Coma Scale (GCS) score, the maximum blood urea nitrogen (BUN) within 24 h, vasopressin and vancomycin usage, and the maximum lactate within 24 h were the top six predictors for short-term reversibility of AKI. The RF model presented the best performance for predicting both renal functional recovery (AU-ROC [0.8295 ± 0.01]) and early recovery (AU-ROC [0.7683 ± 0.03]) compared with the conventional logistic regression model.ConclusionsThe maximum SCr within 24 h of AKI diagnosis was a common independent predictor of renal function recovery and the short-term reversibility of AKI. The RF machine learning algorithms showed a superior ability to predict the prognosis of AKI patients in the ICU compared with the traditional regression models. These models may prove to be clinically helpful and can assist clinicians in providing timely interventions, potentially leading to improved prognoses.     

急性Stanford A型主动脉夹层术后急性肾损伤的肾叶间动脉血流动力学改变

目的探讨急性Stanford A型主动脉夹层术后急性肾损伤(AKI)的超声血流动力学指标改变情况。方法收集40例接受手术治疗的急性Stanford A型主动脉夹层患者,分别在手术前1天、术后即刻(进入重症监护室)、手术后6、24、48h测量双肾叶间动脉收缩期峰值流速(PSV)、舒张期最小流速(EDV)、搏动指数(PI)、阻力指数(RI),同时记录血肌酐(sCr)水平和尿量。以AKIN为标准将患者分为AKI组和无AKI组,比较两组间差异。结果 40例患者中,AKI组27例,无AKI组13例。无AKI组与AKI组患者术后6、24h肾叶间动脉EDV、PI、RI差异有统计学意义(P均0.05)。肾叶间动脉EDV与sCr呈负相关(r=-0.508,P=0.001),PI、RI与SCr呈正相关(r=0.411、0.443,P=0.009、0.005)。结论通过肾叶间动脉EDV、PI、RI可早期预测AKI发生,术后6、24h是超声测量肾叶间动脉血流动力学指标预测肾损伤的最佳时间。