Urinary calprotectin,NGAL, and KIM-1 in the differentiation of primarily inflammatory vs. non-inflammatory stable chronic kidney diseases

Introduction It has been demonstrated that urinary neutrophil gelatinase-associated lipocalin (NGAL) and calprotectin are helpful biomarkers in the differentiation of intrinsic and prerenal acute kidney injury.Objective The present cross-sectional study investigates, whether urinary biomarkers are able to differentiate primarily inflammatory from non-inflammatory entities in chronic kidney disease (CKD).Methods Urinary calprotectin, NGAL, and kidney injury molecule-1 (KIM-1) concentrations were assessed in a study population of 143 patients with stable CKD and 29 healthy controls. Stable renal function was defined as an eGFR fluctuation ≤5 ml/min/1.73 m² in the past 12 months. Pyuria, metastatic carcinoma, and renal transplantation were regarded as exclusion criteria. Diabetic nephropathy, hypertensive nephropathy, and polycystic kidney disease were categorized as ‘primarily non-inflammatory renal diseases’ (NIRD), whereas glomerulonephritis and vasculitis were regarded as ‘primarily inflammatory renal diseases’ (IRD).Results Urinary calprotectin and NGAL concentrations significantly differed between CKD and healthy controls (p < 0.05 each), whereas KIM-1 concentrations did not (p = 0.84). The three biomarkers did neither show significant differences in-between the individual entities, nor the two categories of IRD vs. NIRD (calprotectin 155.7 vs. 96.99 ng/ml; NGAL 14 896 vs. 11 977 pg/ml; KIM-1 1388 vs. 1009 pg/ml; p > 0.05 each). Albumin exceeds the diagnostic power of the investigated biomarkers by far.Conclusions The urinary biomarkers calprotectin, NGAL, and KIM-1 have no diagnostic value in the differentiation of primarily inflammatory vs. non-inflammatory etiologies of CKD.     

NGAL基因5′侧翼区转录调控元件的分段定位鉴定

目的 :对中性粒细胞明胶酶相关脂萼蛋白 (neutrophilgelatinase associatedlipocalin ,NGAL)基因 5′侧翼区的转录调控元件进行分段定位鉴定。方法 :以双荧光素酶报告基因检测系统检测NGAL基因 5′侧翼区 ( -14 3 1～ +84)转录调控元件与转录调控蛋白之间的相互作用。结果 :在NGAL基因 5′端 -945～ -65 8和 -65 7～ -4 172个区段发现了转录增强子元件与转录激活蛋白之间的相互作用 ,而在 -4 16～ -15 2区段则发现了转录沉默子元件与转录抑制蛋白之间的相互作用。结论 :在NGAL基因5′侧翼转录调控区可能至少存在着 2个转录增强子元件和 1个转录沉默子元件     

Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

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Predicting long-term outcomes after cardiac arrest by using serum neutrophil gelatinase-associated lipocalin

Objectives

Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by various tissues in pathologic states. Previous studies reported that post-cardiac arrest serum NGAL levels correlate with short-term neurologic outcomes and survival. The aim of this study was to examine the associations between NGAL levels post-cardiac arrest and long-term outcomes and survival.

KIM-1及NGAL在苯酚烧伤致大鼠早期肾损伤中的表达水平及意义

目的 观察肾损伤分子-1（KIM-1）及中性粒细胞明胶酶相关载脂蛋白（NGAL）在苯酚烧伤致大鼠早期肾损伤中的表达水平,并分析其临床意义。方法 将48只SD大鼠随机分为对照组6只、实验组42只,对照组大鼠仅做背部脱毛处理,实验组大鼠建立苯酚烧伤模型,分别于烧伤后15、45 min以及2、4、8、16、32 h观察肾脏组织病理变化,并采用酶联免疫吸附试验（ELISA）法检测KIM-1、NGAL水平,肌氨酸氧化酶法检测血肌酐（Scr）水平,分析KIM-1、NGAL与肾损伤的相关性及其对肾损伤的诊断价值。结果 苯酚烧伤大鼠创面呈浅红色至棕红色、质地稍韧,且伴有全身抽搐及肉眼血尿等表现;苏木精-伊红（HE）染色结果显示,烧伤32 h内大鼠肾脏组织逐渐出现肾小管空泡样变性、蛋白质管型、肾小管扩张、肾小管坏死等病理改变;烧伤后32 h内大鼠血清KIM-1、NGAL水平均呈先升高后降低的趋势,其中KIM-1水平于烧伤后15 min开始升高,8 h到达高峰;NGAL水平于烧伤后2 h开始升高,16 h到达高峰;而Scr水平升高不明显;血清KIM-1、NGAL水平与早期肾损伤具有显著相关性（r=0.664、0.730,P均＜0.001）,两者联合检测对诊断早期肾损伤具有显著优势。结论 血清KIM-1及NGAL水平与苯酚烧伤致大鼠早期肾损伤程度密切相关,对诊断苯酚烧伤致大鼠早期肾损伤具有较高的临床应用价值。     

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.     

Neutrophil gelatinase associated lipocalin as an indicator of acute kidney injury and inflammation in burned children

Introduction

Neutrophil gelatinase associated lipocalin (NGAL) is a novel predictor of acute kidney injury (AKI), which increases with inflammation. We aimed to assess whether serum NGAL (SNGAL) and urine NGAL (UNGAL) can predict AKI in burned children.

Methods

Patients were referred within the 12 h of burn to our center. Serum samples for SNGAL, C-reactive protein (CRP), procalcitonin (PCT) and urine for UNGAL, microalbumine (Umalb), creatinine (Ucr) were obtained at both admission and the 5th day after burn. Blood urea nitrogen (BUN) and serum creatinine (Scr) were examined daily.

Results

Twenty-two subjects were enrolled and six (27.2%) of them developed AKI within the 48 h of injury. Burn size and abbreviated burn severity index (ABSI) were significantly increased in patients with AKI. CRP, PCT, SNGAL and UNGAL levels at admission and day 5 were significantly higher in patients with AKI than in those without AKI and controls. Scr was not significant between AKI and non-AKI groups at hospital days 1 and 5. A SNGAL level of 315 ng/ml and a UNGAL level of 100 ng/ml were determined as predictive cut-off values of AKI at admission (sensitivity and specificity: 71.4%, 83.3% and 93.3%, 93.7%, respectively). SNGAL and UNGAL were positively correlated with CRP, PCT, ABSI and Umalb/Ucr.

Conclusion

SNGAL and UNGAL are good early predictors of AKI in children with severe burn. NGAL might reflect the severity of burn insult and also could be used as an indicator of inflammation in burn children.