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Plasma neutrophil-gelatinase-associated lipocalin and cystatin C could early diagnose contrast-induced acute kidney injury in patients with renal insufficiency undergoing an elective percutaneous coronary intervention

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Chinese Medical Journal 2012年第6期125卷 1051-1056页

作者： LIU Xiao-li WANG Zhi-jian YANG Qing YU Miao SHEN Hua NIE Bin HAN Hong-ya GAO Fei ZHOU Yu-jie Department of Cardiology Anzhen HospitalCapital Medical UniversityBeijing 100029China

Background Contrast induced acute kidney injury （CIAKI） is an important complication in the use of iodinated contrast media （CM）. Our study was to evaluate the neutrophil gelatinase-associated lipocalin （NGAL） and cystatin C for early diagnosis of CIAKI. Methods The patients with established or suspected coronary artery disease （CAD） with the estimated glomerular filtration rate （eGFR） was more than 30 ml·min^-1·1.73 m^-2 and nor more than 90 ml·min^-1·1.73 m^-2 were continuously enrolled. The blood samples of the first 50 patients were obtained before and at 2, 4, 8, 24 and 48 hours after procedure to identify the time points at which the biomarkers reached peaks and at which the blood samples of the rest of patients were obtained. The plasma NGAL and cystatin C measure used enzyme-linked immunosorbent assay （ELISA） kit. The diagnostic characteristics of absolute and relative increasing NGAL and cystatin C for CIAKI were evaluated. Results Total 311 patients were enrolled, among whom 39 （12.5%） developed CIAKI. Plasma NGAL increased at 2 hours and reached peak at 4 hours after procedure, while plasma cystatin C increased at 2 hours and reached peak at 24 hours after procedure. Thus, we determine rational point of time at 4 hours for NGAL and at 24 hours after procedure for cystatin C, respectively. The plasma NGAL at 4 hours after CM exposure showed largest area under curve （AUC） of 0.662 （95% confidence interval （CI）： 0.565-0.758, P=0.002） with 51.5% sensitivity and 80.6% of specificity. The relative increasing 25% of NGAL showed the best sensitivity and specificity of 0.872 and 0.808, respectively, with maximum Youden index of 0.680, while cystatin C with relative increasing more than 25% had 76.9% of sensitivity and 81.2% of specificity. Combined two biomarkers might get more than 90% of specificity. Conclusions Single measurement of NGAL or cystatin C had poor sensitivity and specificity; however, the relative increasing 25% of NGAL at 4 hours after CM exposure

关键词： acute kidney injury early diagnosis neutrophil gelatinase-associated lipocalin cystatin C

Renal Doppler and Novel Biomarkers to Assess acute kidney injury in a Swine Model of Ventricular Fibrillation Cardiac Arrest

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Chinese Medical Journal 2015年第22期128卷 3069-3075页

作者： Xue Mei Chen-Chen Hang Shuo Wang Chun-Sheng Li Ze-Xing Yu Department of Emergency Beijing Chao-Yang HospitaL Capital Medical University Beijing 100020 China Department of Ultrasound Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China

Background： Majority of the research on cardiac arrest （CA） have focused on post-CA brain injury and myocardial dysfunction, the renal dysfunction and acute kidney injury （AKI） in other critical illnesses after CA have not been well described. This study was designed to assess AKI with renal Doppler and novel AK1 biomarkers in a swine model of ventricular fibrillation cardiac arrest （VFCA）. Methods： Thirty healthy piglets were divided into VFCA group （17 = 22） and Sham group （n = 8） in a blinded manner. Mean arterial pressure, heart rate. and cardiac output were recorded continuously. Cardiac arrest （CA） was induced by programmed electric stimulation in the VFCA group, and then cardiopulmonary resuscitation was performed. Twenty piglets returned of spontaneous circulation （ROSC） and received intensive care. Blood and urine samples were collected for AKI biomarkers testing, and Color Doppler flow imaging was performed at baseline, 6 h, 12 h, and 24 11. respectively after ROSC. At ROSC 24 h, the animals were sacrificed and a semi-quantitative evaluation of pathologic kidney injury was performed. Results： In the VFCA group, corrected resistive index （cRl） increased from 0.47 ± 0.03 to 0.64 ± 0.06, and pulsatility index （PI） decreased from 0.82 ± 0.03 to 0.68 ± 0.04 after ROSC. Cystatin C （CysC） in both serum and urine samples increased at ROSC 6 h, but neutrophil gelatinase-associated lipocalin （NGAL） in serum increased to 5.34 ± 1.68 ng/ml at ROSC 6 h, and then decreased to 3.16 ± 0.69 ng/ml at ROSC 24 h while CysC increasing constantly. According to the renal histopathology, 18 of 20 animals suffered from kidney injury. The grade of renal injury was highly correlated with RI, cRI, NGAL, and CysC. Linear regression equation was established： Grade of renal injury = 0.002× serum CysC ＋ 6.489 × PI ＋ 4.544 × cRI - 8.358 （r^2 = 0.698, F = 18.506, P 〈 0.001）. Conclusions： AKI is common in post-CA syndrome. Renal Doppler and novel AKI biomarkers in serum and urine are of sig

关键词： acute kidney injury Cardiac Arrest Cystatin C Doppler Ultrasonography Neutrophil Gelatinase-associated Lipocalin

Predictive Value of Serum Creatinine, Blood Urea Nitrogen,Uric Acid, and β2-Microglobulin in the Evaluation of acute kidney injury after Orthotopic Liver Transplantation

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Chinese Medical Journal 2018年第9期131卷 1059-1066页

作者： Hai-Yang Lu Xin-Yu Ning Ying-Qi Chen Shu-Jun Han Ping Chi Sai-Nan Zhu Yun Yue Department of Anaesthesiology Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China Department of Anaesthesiology Beijing You An Hospital Capital Medical University Beijing 100069 China Department of Anaesthesiology Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University Beijing 102218 China Department of Anaesthesiology The General Hospital of the Chinese People's Armed Police Forces Beijing 100039 China Department of Biostatistics Peking University First Hospital Beijing 100034 China

Background：As a major complication after orthotopic liver transplantation （OLT）,the occurrence of acute kidney injury （AKI） is frequently defined by serum creatinine （Cr）;however,the accuracy of commonly used blood urea nitrogen （BUN）,uric acid （UA）,and β2-microglobulin （β2-MG） remains to be *** retrospective study compared the accuracy of these parameters for post-OLT AKI ***：Patients who underwent OLT in three centers between July 2003 and December 2013 were *** postoperative AKI group was diagnosed by the kidney Disease Improving Global Outcomes （KDIGO） criteria and classified by *** data were analyzed using the t-test or Wilcoxon rank-sum test;enumerated data were analyzed using the Chi-square test or Fisher＇s exact *** reliability and predictive accuracy were evaluated using receiver operating characteristic （ROC） curve ***：This study excluded 976 cases and analyzed 697 patients （578 men and 1 1 9 women）;the post-OLT AKI incidence was *** with the no-AKI group,the AKI group showed very significant differences in Model for End-stage Liver Disease score （14.74 ± 9.91 vs.11.07 ± 9.54,Z =5.404;P ＜ 0.001）,hepatic encephalopathy （45 [15.8％] vs.30 [7.3％],x2 =12.699;P ＜ 0.001）,hemofiltration （28 [9.8％] vs.0 [0.0％],x2 =42.171;P ＜ 0.001）,and 28-day mortality （23 [8.1％] vs.9 [2.2％],x2 13.323;P ＜0.001）.Moreover,mean values of Cr,BUN,UA,and β2-MG in the AKI group differed significantly at postoperative days 1,3,and 7 （all P ＜0.001）.ROC curve area was 0.847 of Cr for the detection of AKI Stage 1 （sensitivity 80.1％,specificity 75.7％,cutoffvalue 88.23 μmol/L）,0.916 for Stage 2 （sensitivity 87.6％,specificity 82.6％,cutoff value 99.9 μmol/L）,and 0.972 for Stage 3 （sensitivity 94.1％,specificity 88.2％,cutoff value 122.90 μmol/L）.Conclusion：The sensitivity and specificity of serum Cr might be a high-value indicator for the diagnosis and grading of post-OLT AKI.

关键词： acute kidney injury Blood Urea Nitrogen Creatinine Liver Transplantation Uric Acid β2-Microglobulin

Epidemiology of acute kidney injury in intensive care septic patients based on the KDIGO guidelines

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Chinese Medical Journal 2014年第10期127卷 1820-1826页

作者： Peng Qianyi Zhang Lina Ai Yuhang Zhang Lemeng Department of Critical Care Medicine Xiangya Hospital Central South University Changsha Hunan 410008 China

Background acute kidney injury （AKI） is a common complication of sepsis,which is associated with higher risks of adverse ***,kidney disease：improving global outcomes （KDIGO） recommended a new guideline forAKI,including a little modification on the AKI staging *** This retrospective study included 211 septic patients admitted to the intensive care unit （ICU） at Xiangya Hospital,Central South University from January 2008 to January *** was diagnosed and classified according to the KDIGO or acute kidney injury network （AKIN） *** between the AKI and non-AKI groups for baseline characteristics,laboratory examinations,etiology,outcomes,as well as the risk factors for AKI and 28-day mortality were *** reliability of the KDIGO criteria was also evaluated by comparing it with the AKIN *** The overall incidence of AKI in septic patients was 47.9％,and the 28-day mortality was 32.7％.The incidence of AKI was significantly higher in patients with more severe *** of hepatic and respiratory function were significantly worse in the AKI ***,a higher proportion of patients were infected with Enterobacter cloacae in the AKI *** independent risk factors for AKI were shock,the number of organ failures,blood urea nitrogen （BUN）levels,and the use of *** independent risk factors for mortality were BUN and creatine kinase-MB （CK-MB）*** the KDIGO criteria and the AKIN criteria were significantly associated with 28-day *** The incidence and 28-day mortality of AKI were very high in ICU septic *** attention should be paid to AKI-induced hepatic and respiratory dysfunction in clinical *** with an intra-abdominal source of infection were more likely to develop *** criteria are reliable in AKI staging.

关键词： acute kidney injury sepsis epidemiology risk factors KDIGO

Prognostic Value of Model for End-Stage Liver Disease Incorporating with Serum Sodium Score for Development of acute kidney injury after Liver Transplantation

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Chinese Medical Journal 2018年第11期131卷 1314-1320页

作者： Yuan Cheng Guo-Qing Wei Qiu-Cheng Cai Yi Jiang Ai-Ping Wu Department of Hepatobiliary Surgery Fuzhou General Hospital Fuzhou Fujian 350025 China Department of Comparative Medicine Fuzhou General Hospital Fuzhou Fujian 350025 China

Background： Contribution of model for end-stage liver disease incorporating with serum sodium （MELD-Na） score in predicting acute kidney injury （AKI） after orthotopic liver transplantation （OLT） is yet to be identified. This study assessed the prognostic value ot MELD-Na score for the development of AKl following OLT. Methods： Preoperative and surgery-related variables of 321 adult end-stage liver disease patients who underwent OLT in Fuzhou General Hospital were collected. PostoperativeAKI was defined and staged in accordance with the clinical practice guidelines developed by kidney Disease： Improving Global Outcomes. Univariate and multivariate analysis was performed to determine the risk factors fnr AKI following OLT. The discriminating power of MELD/MELD-Na score on AKI outcome was evaluated by receiver operating characteristic （ROC） curve. Spearman＇s correlation analysis was used for identifying the correlated relationship between MELD/MELD-Na score and the severity levels of AKI. Results： The prevalence of AKI following OLT was in 206 out of 321 patients （64.2%）. Three risk lhctors for AKI post-OLT were presented, preoperative calculated MELD score （odds ratio [OR] = 1.048, P = 0.021）, intraoperative volume of red cell suspension transfusion （OR = 1.001, P 0.002）, and preoperative liver cirrhosis （OR = 2.015, P = 0.012）. Two areas under ROC curve （AUCs） of MELD/MELD-Na score predicting AKI were 0.688 and 0.672, respectively; the difference between two AUCs was not significant （Z= 1.952, P = 0.051）. The Spearman＇s correlation coefficients between MELD/MELD-Na score and the severity levels of AKI were 0.406 and 0.385 （P 0.001, 0.001）, respectively. Conclusions： We demonstrated that preoperative MELD score, intraoperative volume of red cell suspension transfusion and preoperative liver cirrhosis were risk factors for AKI following OLT. Furthermore, we preliminarily validated that MELD score seemed to have a stronger power discriminating AKI post-OLT than that of

关键词： acute kidney injury Liver Transplantation Model for End-Stage Liver Disease Score

MicroRNA-21 in the pathogenesis of acute kidney injury

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Protein & Cell 2013年第11期4卷 813-819页

作者： Ya-Feng Li Ying Jing Jielu Hao Nathan C Frankfort Xiaoshuang Zhou Bing Shen Xinyan Liu Lihua Wang Rongshan Li Department of Nephrology and Hemodialysis Center Second Hospital of Shanxi Medical UniversityTaiyuan 030001China Shanxi Renal Disease Research Institution Taiyuan 030001China Department of Blood Purifi cation General Hospital of Jinan Military Command of PLAJinan 250031China Nephrology Institute of PLA Changzheng Hospital of Second Military Medical UniversityShanghai 200003China Department of Neuroscience and Neurovirology Temple University School of MedicinePhiladelphiaPA 19140USA Department of Urology Shanghai First People’s HospitalShanghai 200080China Department of Nephrology and Hemodialysis Center Shanxi Provincial People’s HospitalTaiyuan 030012China

acute kidney injury(AKI),associated with significant mor-bidity and mortality,is widely known to involve epithelial apoptosis,excessive inflammation,and fibrosis in re-sponse to ischemia or reperfusion injury,which results in either chronic pathological changes or ***,it is imperative that investigations are conducted in order to fi nd effective,early diagnoses,and therapeutic targets needed to help prevent and treat ***,the mech-anisms modulating the pathogenesis of AKI still remain largely ***(miRNAs),small non-coding RNA molecules,play an important role in several fundamental biological and pathological processes by a post transcriptional regulatory function of gene ***-21(miR-21)is a recently identifi ed,typi-cal miRNA that is functional as a regulator known to be involved in apoptosis as well as inflammatory and fi brotic signaling pathways in *** a result,miR-21 is now considered a novel biomarker when diagnosing and treat-ing *** article reviews the correlative literature and research progress regarding the roles of miR-21 in AKI.

关键词： microRNA microRNA-21 gene expression acute kidney injury

Plasmacytoid dendritic cells promote acute kidney injury by producing interferon-α

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Cellular & Molecular Immunology 2021年第1期18卷 219-229页

作者： Bo Deng Yuli Lin Yusheng Chen Shuai Ma Qian Cai Wenji Wang Bingji Li Tingyan Liu Peihui Zhou Rui He Feng Ding Division of Nephrology Shanghai Ninth Peopled HospitalSchool of MedicineShanghai Jiaotong University200011 ShanghaiChina Department of Immunology and Key Laboratory of Medical Molecular Virology of Ministries of Education and Health School of Basic Medical SciencesFudan University200032 ShanghaiChina Institutes of Integrative Medicine Fudan University200032 ShanghaiChina Department of Gastrointestinal Surgery Shanghai Pudong HospitalFudan University Pudong Medical Center200120 ShanghaiChina

acute kidney injury(AKI)is a common clinical complication associated with high mortality in *** cells and cytokines have recently been described to play essential roles in AKI *** dendritic cells(pDCs)are a unique DC subset that specializes in type Ⅰ interferon(IFN)***,we showed that pDCs rapidly infiltrated the kidney in response to AKI and contributed to kidney damage by producing IFN-α.Deletion of pDCs using DTR^(BDCA2) transgenic(Tg)mice suppressed cisplatin-induced AKI,accompanied by marked reductions in proinflammatory cytokine production,immune cell infiltration and apoptosis in the *** contrast,adoptive transfer of pDCs during AKI exacerbated kidney *** further identified IFN-α as the key factor that mediated the functions of pDCs during AKI,as IFN-α neutralization significantly attenuated kidney ***,IFN-α produced by pDCs directly induced the apoptosis of renal tubular epithelial cells(TECs)in *** addition,our data demonstrated that apoptotic TECs induced the activation of pDCs,which was inhibited in the presence of an apoptosis ***,similar deleterious effects of pDCs were observed in an ischemia reperfusion(IR)-induced AKI ***,increased expression of IFN-α in kidney biopsies was observed in kidney transplants with *** together,the results of our study reveal that pDCs play a detrimental role in AKI via IFN-α.

关键词： acute kidney injury cisplatin nephrotoxicity plasmacytoid dendritic cells interferon-α

Effect of Platelet-derived P-selectin on Neutrophil Recruitment in a Mouse Model of Sepsis-induced acute kidney injury

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Chinese Medical Journal 2017年第14期130卷 1694-1699页

作者： Xiu-Hua Li Yong-Bing Qian Xiao-Xiao Meng Rui-Lan Wang Department of Critical Care Medicine Shanghai General Hospital of Nanjing Medical University Shanghai 201620 China Emergency Center Shanghai East Hospital Tongji University School of Medicine Shanghai 200120 China

Background：acute kidney injury （AKI） is a severe disease in critically ill *** infiltration into kidney was associated with the development of AKI,and P-selectin may be involved in the process of neutrophil recruitment in *** study aimed to explore the potential effect of platelet-derived P-selectin on neutrophil recruitment in a mouse model of sepsis-induced ***：A total of 30 C57BL/6 male mice were divided into five groups （n =6 in each）：sham group,sepsis group,anti-Ly6G group,anti-P-selectin group,and platelet depletion *** was induced by cecal ligation and *** creatinine concentration and platelet activity were measured by biochemical detector and flow cytometry,*** and pathological features were analyzed using hematoxylin-eosin （HE） and immunohistochemi stry （IHC） staining,*** （M PO） activity was detected with MPO *** t-test was used for data ***：Serum creatinine increased significantly in septic group compared to sham group （2.68 ± 0.27 mg/dl vs.0.82 ± 0.19 mg/dl,t =12.06,P =0.0000） but attenuated in antibodies-treated animals compared to septic group （anti-Ly6G：1.62 ± 0.30 mg/dl vs.2.68 ± 0.27 mg/dl,t =5.76,P=0.0004;anti-P-selectin：1.76 ± 0.31 mg/dl vs.2.68 ± 0.27 mg/dl,t =4.92,P =0.0012;and platelet depletion：1.93 ± 0.29 mg/dl vs.2.68 ± 0.27 mg/dl,t =4.14,P =0.0032）.Platelet amount significantly decreased compared to sham group （658.20 ± 60.64 × 109/L vs.822.00 ± 48.60 × 109/L,t =4.71,P =0.0015） in septic mice,especially in platelet depletion group （240.80 ± 44.98 × 109/L vs.822.00 ± 48.60 × 109/L,t =19.63,P =0.0000）.P-selectin activity was significantly increased in septic group compared to sham group （16.54 ± 1.60% vs.1.90 ± 0.29%,t =15.64,P =0.0000） but decreased significantly in platelet depletion group compared to septic group （3.62 ± 0.68% vs.16.54 ± 1.60%,t =12.89,P =0.0002）.IHC analysis shown that neutrophil infiltration increased

关键词： acute kidney injury Neutrophils P-Selectin Sepsis

Pharmacological Inhibition of Macrophage Toll-like Receptor 4/Nuclear Factor-kappa B Alleviates Rhabdomyolysis-induced acute kidney injury

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Chinese Medical Journal 2017年第18期130卷 2163-2169页

作者： Rong-Shuang Huang Jiao-Jiao Zhou Yu-Ying Feng Min Shi Fan Guo Shen-Ju Gou Stephen Salerno Jr. Liang Ma Ping Fu kidney Research Institute Department of Internal Medicine Division of Nephrology West China Hospital of Sichuan University Chengdu Sichuan 610041China Division of Ultrasound West China Hospital of Sichuan University Chengdu Sichuan 610041 China Department of Biostatistics School of Public Health University of Michigan Ann Arbor Michigan 48109 USA

Background：acute kidney injury （AKI） is the most common and life-threatening systemic complication *** plays an important role in the development of rhabdomyolysis-induced *** study aimed to investigate the kidney model of AKI caused by rhabdomyolysis to verify the role ofmacrophage Toll-like receptor 4/nuclear factor-kappa B （TLR4/NF-κB） signaling ***：C57BL/6 mice were injected with a 50% glycerin solution at bilateral back limbs to induce rhabdomyolysis,and CLI-095 or pyrrolidine dithiocarbamate （PDTC） was intraperitoneally injected at 0.5 h before *** creatinine levels,creatine kinase,the expression of tumor necrosis factor （TNF）-c,interleukin （IL）-1β and I L-6,and hematoxylin and eosin stainings of kidney tissues were *** infiltration of macrophage,mRNA levels,and protein expression of TLR4 and NF-κB were investigated by immunofluorescence double-staining techniques,reverse transcriptase-quantitative polymerase chain reaction,and Western blotting,*** vitro,macrophage RAW264.7 was stimulated by ferrous myoglobin;the cytokines,TLR4 and NF-κB expressions were also ***：In an in vivo study,using CLI-095 or PDTC to block TLR4/NF-κB,functional and histologic results showed that the inhibition of TLR4 or NF-κB alleviated glycerol-induced renal damages （P 〈 0.0 1）.CLI-095 or PDTC administration suppressed proinflammatory cytokine （TNF-c,IL-6,and IL-1 β） production and macrophage infiltration into the kidney （P 〈 0.01）.Moreover,in an in vitro study,CLI-095 or PDTC suppressed myoglobin-induced expression ofTLR4,NF-κB,and proinflammatory cytokine levels in macrophage RAW264.7 cells （P 〈 0.01）.Conclusion：The pharmacological inhibition of TLR4/NF-κB exhibited protective effects on rhabdomyolysis-induced AKI by the regulation of proinflammatory cytokine production and macrophage infiltration.

关键词： acute kidney injury Macrophages Rhabdomyolysis: Toll-Like Receptor 4 NF-kappa B