BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-...BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.展开更多
BACKGROUND： Acute kidney injury （AKI） is associated with a high mortality. This study was undertaken to detect the factors associated with the prognosis of AKI.METHODS： We retrospectively reviewed 98 patients with...BACKGROUND： Acute kidney injury （AKI） is associated with a high mortality. This study was undertaken to detect the factors associated with the prognosis of AKI.METHODS： We retrospectively reviewed 98 patients with AKI treated from March 2008 to August 2009 at this hospital. In these patients, 60 were male and 38 female. Their age ranged from 19 to 89 years （mean 52.4±16.1 years）. The excluded patients were those who died within 24 hours after admission to ICU or those who had a history of chronic kidney disease or incomplete data. After 60 days of treatment, the patients were divided into a survival group and a death group. Clinical data including gender, age, history of chronic diseases, the worst laboratory values within 24 hours after diagnosis （values of routine blood tests, blood gas analysis, liver and renal function, levels of serum cystatin C, and blood electrolytes） were analyzed. Acute physiology, chronic health evaluation （APACHE） II scores and 60-day mortality were calculated. Univariate analysis was performed to find variables relevant to prognosis, odds ratio （OR） and 95% confidence interval （CI）. Multiple-factor analysis with logistic regression analysis was made to analyze the correlation between risk factors and mortality.RESULTS： The 60-day mortality was 34.7% （34/98）. The APACHE II score of the death group was higher than that of the survival group （17.4±4.3 vs. 14.2±4.8, P〈0.05）. The mortality of the patients with a high level of cystatin C〉1.3 mg/L was higher than that of the patients with a low level of cystatin C （〈1.3 mg/L） （50% vs. 20%, P〈0.05）. The univariate analysis indicated that organ failures≥2, oliguria, APACHE II〉15 scores, cystatin C〉1.3 mg/L, cystatin C〉1.3 mg/L＋APACHE II〉15 scores were the risk factors of AKI. Logistic regression analysis, however, showed that organ failures≥2, oliguria, cystatin C〉1.3 mg/L ＋APACHE II〉15 scores were the independent risk factors of AKI.CONCLUSION： Cystatin C〉1.3 mg/L＋APACHE II〉15 scores is useful in predicting adverseclinical outcomes in patients with AKI.展开更多
Background Acute kidney injury （AKI） is common after surgery for acute aortic dissection （AAD） and increases in-hospital and long-term mortality. However, few data exist on the clinical and prognostic relevance of...Background Acute kidney injury （AKI） is common after surgery for acute aortic dissection （AAD） and increases in-hospital and long-term mortality. However, few data exist on the clinical and prognostic relevance of early preoperative AKI in patients with type A AAD We aimed to determine the incidence and predictors of preoperative AKI and the impact of AKI on in-hospital outcomes in patients with type A AAD. Methods From May 2009 to June 2014, we retrospectively enrolled 178 patients admitted to our hospital within 48 h from symp- tom onset and receiving open surgery for type A AAD. The patients were divided into no AKI and AKI groups and staged with AKI severity according to the KDIGO criteria before surgery. Results AKI occurred in 41 patients （23.0%）. The incidence of in-hospital complications was significantly higher in patients with preoperative AKI compared to no AKI （41.5% vs. 9.5%, P 〈 0.001）, including renal infarction （7.3% vs. 0, P = 0.012）, and it increased with AKI severity （Ptrend〈 0.001）. Patients with AKI had higher in-hospital mortality compared with pa- tients without AKI, although no significant difference was found （14.6% vs. 5.1%, P = 0.079）. Multivariate analysis indicated that male gender, diastolic blood pressure on admission and bilateral renal artery involvement were independent predictors of preoperative AKI in patients with type A AAD. Conclusions Early AKI before surgery was common in patients with type A AAD, and was associated with increased in-hospital complications. Male gender, diastolic blood pressure on admission and bilateral renal artery involvement were major predictors for preoperative AKI.展开更多
BACKGROUND： Serum creatinine （SCr） is the most commonly used parameter to estimate renal function impairement, but there are some shortcomings. Many factors including age, gender, drug, diet, muscle mass and metabo...BACKGROUND： Serum creatinine （SCr） is the most commonly used parameter to estimate renal function impairement, but there are some shortcomings. Many factors including age, gender, drug, diet, muscle mass and metabolic rate can in？ uence SCr, leading to an inaccurate estimation of kidney impairment. Studies have shown that cystatin C （CysC） is not affected by factors such as muscle mass, age, gender, diet, in？ ammation or tumor. The present study was undertaken to compare the sensitivity of CysC and SCr in evaluating renal function impairment at early stage of shock.METHODS： Seventy-one patients aged 38.3±21.4 years, who had been treated at the Emergency Medicine Department of the First Affiliated Hospital, Sun Yat-sen University between February 2006 and June 2007, were studied. They were divided into groups A, B, C, and D according to the shock time. Serum sample was drawn from each patient at 1, 2, 3, 4 hours after shock to determine SCr and CysC. CysC and SCr were determined again at 72 hours and 7 days after shock.RESULTS： CysC increased earlier than SCr in the 71 patients, and CysC decreased slower than SCr when shock was corrected. CysC increased at 1 hour after shock. There was a negative correlationship between CysC, SCr and glomerular filtration rate （GFR）, especially at early stage of shock.CONCLUSIONS： There is renal injury at early stage of shock. CysC is more sensitive than SCr in assessing renal function at the early stage of shock.展开更多
Background:None of study mentioned about contrast-induced acute kidney injury(CI-AKI)in people who have received contrast agents twice within in a short period of time.This study is trying to identify the predictors.M...Background:None of study mentioned about contrast-induced acute kidney injury(CI-AKI)in people who have received contrast agents twice within in a short period of time.This study is trying to identify the predictors.Methods:We enrolled 607 patients between Oct.2010 and Jul.2015 who received contrast agents twice within 30 days in the Department of Cardiology of the General Hospital of Shenyang Military Region.The primary outcome was CI-AKI within 72 h after contrast agent exposure.Patients were divided into groups A(n=559)and group B(n=48)according to whether CI-AKI occurred after the second agent.Results:Patients in group B(CI-AKI occurred after the second agent)had a more rapid heart rate and more usage of diuretics and digitalis.In group B,CI-AKI occurred more frequently after the first agent.Multivariate logistic regression showed that diuretic(P=0.006)and intra-aortic balloon pump(IABP)usage(P=0.012)were independent predictors of CI-AKI after the first agent.Angiotensin-converting enzyme inhibitor/AngiotensinⅡreceptor antagonist(ACEI/ARB)usage(P=0.039),IABP usage(P=0.040)and CI-AKI occurring after administration of the first agent(P=0.015)were independent predictors of CI-AKI after the second.Furthermore,dividing the patients into tertiles of the time interval between the two agents showed that CI-AKI occurred more frequently when the second agent was administered within 1–3 days after the first exposure than within 4–6 days(12.4%vs.5.0%,P=0.008)or≥7 days(12.4%vs.6.4%,P=0.039).Conclusions:Diuretic and IABP usage are independent predictors of CI-AKI following exposure to a first contrast agent.The major predictors of CI-AKI after exposure to a second agent are time since the first contrast exposure,ACEI/ARB usage,and IABP usage.More importantly,a three-day interval between the two agents is associated with a higher incidence of CI-AKI following the second administration.展开更多
Acute kidney injury following percutaneous coronary intervention （PCI） is associated with a worse outcome. However, the risk factors and outcomes of acute kidney injury （AKI） in patients after intracoronary stent ...Acute kidney injury following percutaneous coronary intervention （PCI） is associated with a worse outcome. However, the risk factors and outcomes of acute kidney injury （AKI） in patients after intracoronary stent implantation are still unknown. A retrospective case control study was done in 325 patients who underwent intracoronary stent implantation from January 2010 to March 2011 at the Drum Tower Hospital of Nanjing University School of Medicine. Those were excluded from the study if they had incomplete clinical data. The patients were divided into a normal group and a AKI group according to the standard of post-operation day 7 to identify AKI. The parameters of the patients included： 1） pre-operative ones： age, gender, hypertension, diabetes mellitus, cerebrovascular disease, left ventricular insufficiency, peripheral angiopathy, creatinine, urea nitrogen, estimated glomerular filtration rate （eGFR）, hyperuricemia, proteinuria, emergency operation, hydration, medications （ACEI/ARBs, statins）; 2） intraoperative ones： dose of contrast media, operative time, hypotension; and 3） postoperative one： hypotension. The parameters were analyzed with univariate analysis and multivariate logistical regression analysis. Of the 325 patients, 51（15.7%） developed AKI. Hospital day and in-hospital mortality were increased significantly in the AKI-group. Univariate analysis showed that age, pre-operative parameters （left ventricular insufficiency, peripheral angiopathy, creatinine, urea nitrogen, estimated glomerular filtration rate, hyperuricemia, proteinuria, hydration）, emergency operation, intraoperative parameters （operative time, hypotension） and postoperative hypotension were significantly different. However, multivariate logistic regression analysis revealed that increased age （OR=0.253, 95%CI=0.088-0.727）, pre-operative proteinuria （OR=5.351, 95%CI=2.128-13.459）, pre-operative left ventricular insufficiency （OR=8.704, 95%CI=3.170-23.898）, eGFR〈60 ml/min/1.73 m2 （OR=6.677, 95%CI=1.167-38.193）, prolonged operative time, intraoperative hypotension （OR=25.245, 95%CI=1.001-1.034） were independent risk factors ofAKl. AKI is a common complication and associated with ominous outcome following intracoronary stent implantation. Increased age, pre-operative proteinuria, pre-operative left ventricular insufficiency, pre-operative low estimated glomerular filtration rate, prolonged operative time, intraoperative hypotension were the significant risk factors ofAKl.展开更多
BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS...BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.展开更多
BACKGROUND Acute kidney injury(AKI)after coronary artery bypass graft(CABG)surgery is associated with significant morbidity and mortality.This retrospective study aimed to establish a risk score for postoperative AKI ...BACKGROUND Acute kidney injury(AKI)after coronary artery bypass graft(CABG)surgery is associated with significant morbidity and mortality.This retrospective study aimed to establish a risk score for postoperative AKI in a Chinese population.METHODS A total of 1138 patients undergoing CABG were collected from September 2018 to May 2020 and divided into a derivation and validation cohort.AKI was defined according to the Kidney Disease Improving Global Outcomes(KDIGO)criteria.Multivariable logistic regression analysis was used to determine the independent predictors of AKI,and the predictive ability of the model was determined using a receiver operating characteristic(ROC)curve.RESULTS The incidence of cardiac surgery–associated acute kidney injury(CSA-AKI)was 24.17%,and 0.53%of AKI patients required dialysis(AKI-D).Among the derivation cohort,multivariable logistic regression showed that age≥70 years,body mass index(BMI)≥25 kg/m2,estimated glomerular filtration rate(eGFR)≤60 mL/min per 1.73 m2,ejection fraction(EF)≤45%,use of statins,red blood cell transfusion,use of adrenaline,intra-aortic balloon pump(IABP)implantation,postoperative low cardiac output syndrome(LCOS)and reoperation for bleeding were independent predictors.The predictive model was scored from 0 to32 points with three risk categories.The AKI frequencies were as follows:0-8 points(15.9%),9-17 points(36.5%)and≥18 points(90.4%).The area under of the ROC curve was 0.730(95%CI:0.691-0.768)in the derivation cohort.The predictive index had good discrimination in the validation cohort,with an area under the curve of 0.735(95%CI:0.655-0.815).The model was well calibrated according to the Hosmer-Lemeshow test(P=0.372).CONCLUSION The performance of the prediction model was valid and accurate in predicting KDIGO-AKI after CABG surgery in Chinese patients,and could improve the early prognosis and clinical interventions.展开更多
KIDNEY involvement is common in non-Hodgkin＇s lymphoma （NHL） with incidence up to 30%-40% in autopsy studies. However, it us- ually occurs late in the course of the diseaseand is clinically silent. Clinically overt...KIDNEY involvement is common in non-Hodgkin＇s lymphoma （NHL） with incidence up to 30%-40% in autopsy studies. However, it us- ually occurs late in the course of the diseaseand is clinically silent. Clinically overt renal disease including acute kidney injury （AKI） as its primary manifestation is rarely reported, moreover, Fanconi syndrome （FS） is extremely rare as the main manifestation in NHL. In this report, we presented a case of NHL primarily presenting with FS and AKI due to diffuse interstitial infiltration of NHL cells and emphasized the important role of renal biopsy, especially renal immunohistochemical analysis in the diagnosis of renal diffuse lymphoma.展开更多
Background:Our objective was to identify possible associations between clinical and laboratory variables and the risk of developing acute kidney injury(AKI)in severely injured patients admitted to the Intensive Care U...Background:Our objective was to identify possible associations between clinical and laboratory variables and the risk of developing acute kidney injury(AKI)in severely injured patients admitted to the Intensive Care Unit(ICU)for whom creatine kinase(CK)levels were available.Methods:For this retrospective observational study,we analyzed adult trauma patients admitted to the ICU from 2011 to 2015 at Fundación Valle del Lili(FVL)University Hospital.Our primary outcome was the incidence of AKI.Multivariate regression analysis was used to assess risk factors for this outcome.Results:A total of 315 patients were included.The trauma mechanisms were blunt(n=130),penetrating(n=66)and blast(n=44)trauma.The median[interquartile range,(IQR)of injury severity score(ISS)was 21(16–29).AKI developed in 75 patients(23.8%).Multivariate regression analysis revealed that the thoracic abbreviated injury scale(AIS)value(median(IQR)in the AKI group:3(0–4)],Acute Physiology and Chronic Health Evaluation(APACHE Ⅱ)score[median(IQR)in the AKI group:18(10–27)],CK greater than 5000 U/L,lactic acid concentration at admission,and dobutamine administration were independently associated with AKI.Conclusions:We found that age,APACHE Ⅱ score,thoracic trauma,lactic acidosis,and dobutamine administration were independently associated with AKI.Trauma surgeons need to be aware of the increased odds of AKI if one of these factors is identified during the evaluation and treatment of injured patients.展开更多
BACKGROUND:The study aims to investigate an optimal indicator for changing the filter during the continuous renal replacement therapy(CRRT)in intensive care unit(ICU)patients with acute kidney injury(AKI).METHODS:Pati...BACKGROUND:The study aims to investigate an optimal indicator for changing the filter during the continuous renal replacement therapy(CRRT)in intensive care unit(ICU)patients with acute kidney injury(AKI).METHODS:Patients with AKI requiring CRRT in an ICU were randomly divided into two groups for crossover trial,i.e.,groups A and B.Patients in the group A were firstly treated with continuous veno-venous hemofiltration(CVVH),followed by continuous veno-venous hemodiafiltration(CVVHDF).Patients in the group B were firstly treated with CVVHDF followed by CVVH.Delivered doses of solutes with different molecular weights at the indicated time points between groups were compared.A correlation analysis between the delivered dose and pre-filter pressure(P_(PRE))and transmembrane pressure(P_(TM))was performed.Receiver operating characteristic(ROC)curves were constructed to evaluate the accuracy of P_(TM) as an indicator for filter replacement.RESULTS:A total of 50 cases were analyzed,27 in the group A and 23 in the group B.Delivered doses of different molecular-weight solutes significantly decreased before changing the filter in both modalities,compared with those at the initiation of treatment(all P<0.05).In the late stage of CRRT,the possible rebound of serum medium-molecular-weight solute concentration was observed.P_(TM) was negatively correlated with the delivered dose of medium-molecular-weight solute in both modalities.The threshold for predicting the rebound of serum concentration of medium-molecularweight solute by P_(TM) was 146.5 mm Hg(1 mm Hg=0.133 k Pa).CONCLUSIONS:The filter can be used as long as possible within the manufacturer’s safe use time limits to remove small-molecular-weight solutes.P_(TM) of 146.5 mm Hg may be an optimal indicator for changing the filter in CRRT therapies to remove medium-molecular-weight solutes.展开更多
BACKGROUND:Several risk scoures have been used in predicting acute kidney injury(AKI)of patients undergoing general or specific operations such as cardiac surgery.This study aimed to evaluate the use of two AKI risk s...BACKGROUND:Several risk scoures have been used in predicting acute kidney injury(AKI)of patients undergoing general or specific operations such as cardiac surgery.This study aimed to evaluate the use of two AKI risk scores in patients who underwent non-cardiac surgery but required intensive care.METHODS:The clinical data of patients who had been admitted to ICU during the first 24 hours of ICU stay between September 2009 and August 2010 at the Cancer Institute,Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively collected and analyzed.AKI was diagnosed based on the acute kidney injury network(AKIN) criteria.Two AKI risk scores were calculated:Kheterpal and Abelha factors.RESULTS:The incidence of AKI was 10.3%.Patients who developed AKI had a increased ICU mortality of 10.9%vs.1.0%and an in-hospital mortality of 13.0 vs.1.5%,compared with those without AKI.There was a significant difference between the classification of Kheterpal's AKI risk scores and the occurrence of AKI(P<0.001).There was no significant difference between the number of Abelha's AKI risk scores and the occurrence of AKI(P=0.499).Receiver operating characteristic curves demonstrated an area under the curve of 0.655±0.043(P=0.001,95%confidence interval:0.571-0.739) for Kheterpal's AKI risk score and 0.507±0.044(P=0.879,95%confidence interval:0.422-0.592) for Abelha's AKI risk score.CONCLUSION:Kheterpal's AKI risk scores are more accurate than Abelha's AKI risk scores in predicting the occurrence of AKI in patients undergoing non-cardiac surgery with moderate predictive capability.展开更多
BACKGROUND:To determine the protective role of mesencephalic astrocyte-derived neurotrophic factor(MANF) in regulating sepsis-associated acute kidney injury(S-AKI).METHODS:A total of 96 mice were randomly divided into...BACKGROUND:To determine the protective role of mesencephalic astrocyte-derived neurotrophic factor(MANF) in regulating sepsis-associated acute kidney injury(S-AKI).METHODS:A total of 96 mice were randomly divided into the control group,control+MANF group,S-AKI group,and S-AKI+MANF group.The S-AKI model was established by injecting lipopolysaccharide(LPS) at 10 mg/kg intraperitoneally.MANF(200 μg/kg) was administered to the control+MANF and S-AKI+MANF groups.An equal dose of normal saline was administered daily intraperitoneally in the control and S-AKI groups.Serum and kidney tissue samples were obtained for biochemical analysis.Western blotting was used to detect the protein expression of MANF in the kidney,and enzyme-linked immunosorbent assay(ELISA) was used to determine expression of MANF in the serum,pro-inflammatory cytokines(tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]).Serum creatinine(SCr),and blood urea nitrogen(BUN)were examined using an automatic biochemical analyzer.In addition,the kidney tissue was observed for pathological changes by hematoxylin-eosin staining.The comparison between two groups was performed by unpaired Student’s t-test,and statistics among multiple groups were carried out using Tukey’s post hoc test following one-way analysis of variance(ANOVA).A P-value <0.05 was considered statistically significant.RESULTS:At the early stage of S-AKI,MANF in the kidney tissue was up-regulated,but with the development of the disease,it was down-regulated.Renal function was worsened in the S-AKI group,and TNF-α and IL-6 were elevated.The administration of MANF significantly alleviated the elevated levels of SCr and BUN and inhibited the expression of TNF-α and IL-6 in the kidney.The pathological changes were more extensive in the S-AKI group than in the S-AKI+MANF group.CONCLUSION:MANF treatment may significantly alleviate renal injury,reduce the inflammatory response,and alleviate or reverse kidney tissue damage.MANF may have a protective effect on S-AKI,suggesting a potential treatment for S-AKI.展开更多
Managing patients with heart failure （HF） is a challenging task within itself, but the presence of associated worsening renal function can greatly increase mortality and morbidity. Early diagnosis and treatment is t...Managing patients with heart failure （HF） is a challenging task within itself, but the presence of associated worsening renal function can greatly increase mortality and morbidity. Early diagnosis and treatment is the key to prevent re-hospitalizations and reduce healthcare costs. Biomarkers have long been established as highly sensitive and specific tools in diagnosing and prognosticating patients with HF. Reflecting distinct pathophysiological events and ongoing cellular insult, biomarkers have been proven superior to conventional laboratory tests. Availability of better assays and rapid analysis has allowed the use of biomarkers as point-of-care tests in the emergency department and at the patient＇s bed-side. Acute HF patients often go on to develop worsening renal function, termed as acute cardiorenal syndrome. The growing breadth of studies has shown the implications of combining multiple biomarkers to better chart outcomes and produce desirable results in such patients.展开更多
Neurological complications after cardiac surgery, rang- ing from permanent stroke to transient dysfunction, repre- sent a key issue in the management of geriatric patients. Many patients aged 70 or more have history o...Neurological complications after cardiac surgery, rang- ing from permanent stroke to transient dysfunction, repre- sent a key issue in the management of geriatric patients. Many patients aged 70 or more have history of neurological dysfunctions, which increases the risk of complications and sequelae, Severe neurologic diseases, such as strokes, occur in up to 6% of patients undergoing cardiac surgery. Therefore, in the setting of fragile patients, prevention is more important than treatment. There are several intraop- erative mechanisms of neurological injury, such as embo- lism, inflammation, intraoperative anemia,展开更多
Background:Acute kidney injury(AKI)is the main life-threatening complication of crush syndrome(CS),and myoglobin is accepted as the main pathogenic factor.The pattern recognition receptor retinoicacid-inducible gene I...Background:Acute kidney injury(AKI)is the main life-threatening complication of crush syndrome(CS),and myoglobin is accepted as the main pathogenic factor.The pattern recognition receptor retinoicacid-inducible gene I(RIG-I)has been reported to exert anti-viral effects function in the innate immune response.However,it is not clear whether RIG-I plays a role in CS-AKI.The present research was carried out to explore the role of RIG-I in CS-AKI.Methods:Sprague-Dawley rats were randomly divided into two groups:the sham and CS groups(n=12).After administration of anesthesia,the double hind limbs of rats in the CS group were put under a pressure of 3 kg for 16 h to mimic crush conditions.The rats in both groups were denied access to food and water.Rats were sacrificed at 12 h or 36 h after pressure was relieved.The successful establishment of the CS-AKI model was confirmed by serum biochemical analysis and renal histological examination.In addition,RNA sequencing was performed on rat kidney tissue to identify molecular pathways involved in CS-AKI.Furthermore,NRK-52 E cells were treated with 200μmol/L ferrous myoglobin to mimic CS-AKI at the cellular level.The cells and cell supernatant samples were collected at 6 h or 24 h.Small interfering RNAs(siRNA)was used to knock down RIG-I expression.The relative expression levels of molecules involved in the RIG-I pathway in rat kidney or cells samples were measured by quantitative real-time PCR(qPCR),Western blotting analysis,and immunohistochemistry(IHC)staining.Tumor necrosis factor-α(TNF-α)was d etected by ELISA.Co-immunoprecipitation(Co-IP)assays were used to detect the interaction between RIG-I and myoglobin.Results:RNA sequencing of CS-AKI rat kidney tissue revealed that the different expression of RIG-I signaling pathway.qPCR,Western blotting,and IHC assays showed that RIG-I,nuclear factor kappa-B(NF-κB)P65,p-P65,and the a poptotic marker caspase-3 and cleaved caspase-3 were up-regulated in the CS group(P<0.05).However,the levels of interferon regulatory factor 3(IRF3),p-IRF3 and the antiviral factor interferon-beta(IFN-β)showed no significant c hanges between the sham and CS groups.Co-IP assays showed the interaction between RIG-I and myoglobin in the kidneys of the CS group.Depletion of RIG-I could alleviate the myoglobin induced expression of apoptosis-associated molecules via the NF-κB/caspase-3 axis.C onclusions:RIG-I is a novel damage-associated molecular patterns(DAMPs)sensor for myoglobin and participates in the NF-κB/caspase-3 signaling pathway in CS-AKI.In the development of CS-AKI,specific intervention in the RIG-I p athway might be a potential therapeutic strategy for CS-AKI.展开更多
基金supported by Beijing Natural Science Foundation(No.7222162 to Dr.Hui Liu)。
文摘BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.
文摘BACKGROUND： Acute kidney injury （AKI） is associated with a high mortality. This study was undertaken to detect the factors associated with the prognosis of AKI.METHODS： We retrospectively reviewed 98 patients with AKI treated from March 2008 to August 2009 at this hospital. In these patients, 60 were male and 38 female. Their age ranged from 19 to 89 years （mean 52.4±16.1 years）. The excluded patients were those who died within 24 hours after admission to ICU or those who had a history of chronic kidney disease or incomplete data. After 60 days of treatment, the patients were divided into a survival group and a death group. Clinical data including gender, age, history of chronic diseases, the worst laboratory values within 24 hours after diagnosis （values of routine blood tests, blood gas analysis, liver and renal function, levels of serum cystatin C, and blood electrolytes） were analyzed. Acute physiology, chronic health evaluation （APACHE） II scores and 60-day mortality were calculated. Univariate analysis was performed to find variables relevant to prognosis, odds ratio （OR） and 95% confidence interval （CI）. Multiple-factor analysis with logistic regression analysis was made to analyze the correlation between risk factors and mortality.RESULTS： The 60-day mortality was 34.7% （34/98）. The APACHE II score of the death group was higher than that of the survival group （17.4±4.3 vs. 14.2±4.8, P〈0.05）. The mortality of the patients with a high level of cystatin C〉1.3 mg/L was higher than that of the patients with a low level of cystatin C （〈1.3 mg/L） （50% vs. 20%, P〈0.05）. The univariate analysis indicated that organ failures≥2, oliguria, APACHE II〉15 scores, cystatin C〉1.3 mg/L, cystatin C〉1.3 mg/L＋APACHE II〉15 scores were the risk factors of AKI. Logistic regression analysis, however, showed that organ failures≥2, oliguria, cystatin C〉1.3 mg/L ＋APACHE II〉15 scores were the independent risk factors of AKI.CONCLUSION： Cystatin C〉1.3 mg/L＋APACHE II〉15 scores is useful in predicting adverseclinical outcomes in patients with AKI.
基金This study was supported in part by grants from the Beijing Natural Science Foundation （7141003）, Beijing Municipal Science ＆ Technology Commission （Z14110700 2514014）, and Beijing Municipal Administration of Hospitals Incubating Program （PX2016048）.
文摘Background Acute kidney injury （AKI） is common after surgery for acute aortic dissection （AAD） and increases in-hospital and long-term mortality. However, few data exist on the clinical and prognostic relevance of early preoperative AKI in patients with type A AAD We aimed to determine the incidence and predictors of preoperative AKI and the impact of AKI on in-hospital outcomes in patients with type A AAD. Methods From May 2009 to June 2014, we retrospectively enrolled 178 patients admitted to our hospital within 48 h from symp- tom onset and receiving open surgery for type A AAD. The patients were divided into no AKI and AKI groups and staged with AKI severity according to the KDIGO criteria before surgery. Results AKI occurred in 41 patients （23.0%）. The incidence of in-hospital complications was significantly higher in patients with preoperative AKI compared to no AKI （41.5% vs. 9.5%, P 〈 0.001）, including renal infarction （7.3% vs. 0, P = 0.012）, and it increased with AKI severity （Ptrend〈 0.001）. Patients with AKI had higher in-hospital mortality compared with pa- tients without AKI, although no significant difference was found （14.6% vs. 5.1%, P = 0.079）. Multivariate analysis indicated that male gender, diastolic blood pressure on admission and bilateral renal artery involvement were independent predictors of preoperative AKI in patients with type A AAD. Conclusions Early AKI before surgery was common in patients with type A AAD, and was associated with increased in-hospital complications. Male gender, diastolic blood pressure on admission and bilateral renal artery involvement were major predictors for preoperative AKI.
文摘BACKGROUND： Serum creatinine （SCr） is the most commonly used parameter to estimate renal function impairement, but there are some shortcomings. Many factors including age, gender, drug, diet, muscle mass and metabolic rate can in？ uence SCr, leading to an inaccurate estimation of kidney impairment. Studies have shown that cystatin C （CysC） is not affected by factors such as muscle mass, age, gender, diet, in？ ammation or tumor. The present study was undertaken to compare the sensitivity of CysC and SCr in evaluating renal function impairment at early stage of shock.METHODS： Seventy-one patients aged 38.3±21.4 years, who had been treated at the Emergency Medicine Department of the First Affiliated Hospital, Sun Yat-sen University between February 2006 and June 2007, were studied. They were divided into groups A, B, C, and D according to the shock time. Serum sample was drawn from each patient at 1, 2, 3, 4 hours after shock to determine SCr and CysC. CysC and SCr were determined again at 72 hours and 7 days after shock.RESULTS： CysC increased earlier than SCr in the 71 patients, and CysC decreased slower than SCr when shock was corrected. CysC increased at 1 hour after shock. There was a negative correlationship between CysC, SCr and glomerular filtration rate （GFR）, especially at early stage of shock.CONCLUSIONS： There is renal injury at early stage of shock. CysC is more sensitive than SCr in assessing renal function at the early stage of shock.
基金supported by Chinese Medical Doctor Association Discovery-Fund Project,Grant/Award Number(DFCMDA201417)National Basic Research Program of China,Grant/Award Number(2012CB517804)。
文摘Background:None of study mentioned about contrast-induced acute kidney injury(CI-AKI)in people who have received contrast agents twice within in a short period of time.This study is trying to identify the predictors.Methods:We enrolled 607 patients between Oct.2010 and Jul.2015 who received contrast agents twice within 30 days in the Department of Cardiology of the General Hospital of Shenyang Military Region.The primary outcome was CI-AKI within 72 h after contrast agent exposure.Patients were divided into groups A(n=559)and group B(n=48)according to whether CI-AKI occurred after the second agent.Results:Patients in group B(CI-AKI occurred after the second agent)had a more rapid heart rate and more usage of diuretics and digitalis.In group B,CI-AKI occurred more frequently after the first agent.Multivariate logistic regression showed that diuretic(P=0.006)and intra-aortic balloon pump(IABP)usage(P=0.012)were independent predictors of CI-AKI after the first agent.Angiotensin-converting enzyme inhibitor/AngiotensinⅡreceptor antagonist(ACEI/ARB)usage(P=0.039),IABP usage(P=0.040)and CI-AKI occurring after administration of the first agent(P=0.015)were independent predictors of CI-AKI after the second.Furthermore,dividing the patients into tertiles of the time interval between the two agents showed that CI-AKI occurred more frequently when the second agent was administered within 1–3 days after the first exposure than within 4–6 days(12.4%vs.5.0%,P=0.008)or≥7 days(12.4%vs.6.4%,P=0.039).Conclusions:Diuretic and IABP usage are independent predictors of CI-AKI following exposure to a first contrast agent.The major predictors of CI-AKI after exposure to a second agent are time since the first contrast exposure,ACEI/ARB usage,and IABP usage.More importantly,a three-day interval between the two agents is associated with a higher incidence of CI-AKI following the second administration.
文摘Acute kidney injury following percutaneous coronary intervention （PCI） is associated with a worse outcome. However, the risk factors and outcomes of acute kidney injury （AKI） in patients after intracoronary stent implantation are still unknown. A retrospective case control study was done in 325 patients who underwent intracoronary stent implantation from January 2010 to March 2011 at the Drum Tower Hospital of Nanjing University School of Medicine. Those were excluded from the study if they had incomplete clinical data. The patients were divided into a normal group and a AKI group according to the standard of post-operation day 7 to identify AKI. The parameters of the patients included： 1） pre-operative ones： age, gender, hypertension, diabetes mellitus, cerebrovascular disease, left ventricular insufficiency, peripheral angiopathy, creatinine, urea nitrogen, estimated glomerular filtration rate （eGFR）, hyperuricemia, proteinuria, emergency operation, hydration, medications （ACEI/ARBs, statins）; 2） intraoperative ones： dose of contrast media, operative time, hypotension; and 3） postoperative one： hypotension. The parameters were analyzed with univariate analysis and multivariate logistical regression analysis. Of the 325 patients, 51（15.7%） developed AKI. Hospital day and in-hospital mortality were increased significantly in the AKI-group. Univariate analysis showed that age, pre-operative parameters （left ventricular insufficiency, peripheral angiopathy, creatinine, urea nitrogen, estimated glomerular filtration rate, hyperuricemia, proteinuria, hydration）, emergency operation, intraoperative parameters （operative time, hypotension） and postoperative hypotension were significantly different. However, multivariate logistic regression analysis revealed that increased age （OR=0.253, 95%CI=0.088-0.727）, pre-operative proteinuria （OR=5.351, 95%CI=2.128-13.459）, pre-operative left ventricular insufficiency （OR=8.704, 95%CI=3.170-23.898）, eGFR〈60 ml/min/1.73 m2 （OR=6.677, 95%CI=1.167-38.193）, prolonged operative time, intraoperative hypotension （OR=25.245, 95%CI=1.001-1.034） were independent risk factors ofAKl. AKI is a common complication and associated with ominous outcome following intracoronary stent implantation. Increased age, pre-operative proteinuria, pre-operative left ventricular insufficiency, pre-operative low estimated glomerular filtration rate, prolonged operative time, intraoperative hypotension were the significant risk factors ofAKl.
基金funded by the Shenzhen Key Medical Discipline Construction Fund(S ZXK046)the National Nature Science Foundation of China(81571869).
文摘BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.
基金supported by National Natural S cience Foundation of China(81570373)。
文摘BACKGROUND Acute kidney injury(AKI)after coronary artery bypass graft(CABG)surgery is associated with significant morbidity and mortality.This retrospective study aimed to establish a risk score for postoperative AKI in a Chinese population.METHODS A total of 1138 patients undergoing CABG were collected from September 2018 to May 2020 and divided into a derivation and validation cohort.AKI was defined according to the Kidney Disease Improving Global Outcomes(KDIGO)criteria.Multivariable logistic regression analysis was used to determine the independent predictors of AKI,and the predictive ability of the model was determined using a receiver operating characteristic(ROC)curve.RESULTS The incidence of cardiac surgery–associated acute kidney injury(CSA-AKI)was 24.17%,and 0.53%of AKI patients required dialysis(AKI-D).Among the derivation cohort,multivariable logistic regression showed that age≥70 years,body mass index(BMI)≥25 kg/m2,estimated glomerular filtration rate(eGFR)≤60 mL/min per 1.73 m2,ejection fraction(EF)≤45%,use of statins,red blood cell transfusion,use of adrenaline,intra-aortic balloon pump(IABP)implantation,postoperative low cardiac output syndrome(LCOS)and reoperation for bleeding were independent predictors.The predictive model was scored from 0 to32 points with three risk categories.The AKI frequencies were as follows:0-8 points(15.9%),9-17 points(36.5%)and≥18 points(90.4%).The area under of the ROC curve was 0.730(95%CI:0.691-0.768)in the derivation cohort.The predictive index had good discrimination in the validation cohort,with an area under the curve of 0.735(95%CI:0.655-0.815).The model was well calibrated according to the Hosmer-Lemeshow test(P=0.372).CONCLUSION The performance of the prediction model was valid and accurate in predicting KDIGO-AKI after CABG surgery in Chinese patients,and could improve the early prognosis and clinical interventions.
文摘KIDNEY involvement is common in non-Hodgkin＇s lymphoma （NHL） with incidence up to 30%-40% in autopsy studies. However, it us- ually occurs late in the course of the diseaseand is clinically silent. Clinically overt renal disease including acute kidney injury （AKI） as its primary manifestation is rarely reported, moreover, Fanconi syndrome （FS） is extremely rare as the main manifestation in NHL. In this report, we presented a case of NHL primarily presenting with FS and AKI due to diffuse interstitial infiltration of NHL cells and emphasized the important role of renal biopsy, especially renal immunohistochemical analysis in the diagnosis of renal diffuse lymphoma.
基金supported in part by the National Institutes of Health John E.Fogarty International Center grant#D43 TW007560。
文摘Background:Our objective was to identify possible associations between clinical and laboratory variables and the risk of developing acute kidney injury(AKI)in severely injured patients admitted to the Intensive Care Unit(ICU)for whom creatine kinase(CK)levels were available.Methods:For this retrospective observational study,we analyzed adult trauma patients admitted to the ICU from 2011 to 2015 at Fundación Valle del Lili(FVL)University Hospital.Our primary outcome was the incidence of AKI.Multivariate regression analysis was used to assess risk factors for this outcome.Results:A total of 315 patients were included.The trauma mechanisms were blunt(n=130),penetrating(n=66)and blast(n=44)trauma.The median[interquartile range,(IQR)of injury severity score(ISS)was 21(16–29).AKI developed in 75 patients(23.8%).Multivariate regression analysis revealed that the thoracic abbreviated injury scale(AIS)value(median(IQR)in the AKI group:3(0–4)],Acute Physiology and Chronic Health Evaluation(APACHE Ⅱ)score[median(IQR)in the AKI group:18(10–27)],CK greater than 5000 U/L,lactic acid concentration at admission,and dobutamine administration were independently associated with AKI.Conclusions:We found that age,APACHE Ⅱ score,thoracic trauma,lactic acidosis,and dobutamine administration were independently associated with AKI.Trauma surgeons need to be aware of the increased odds of AKI if one of these factors is identified during the evaluation and treatment of injured patients.
基金supported by Kunshan Science and Technology Special Fund(Social Development Category,KS18040)。
文摘BACKGROUND:The study aims to investigate an optimal indicator for changing the filter during the continuous renal replacement therapy(CRRT)in intensive care unit(ICU)patients with acute kidney injury(AKI).METHODS:Patients with AKI requiring CRRT in an ICU were randomly divided into two groups for crossover trial,i.e.,groups A and B.Patients in the group A were firstly treated with continuous veno-venous hemofiltration(CVVH),followed by continuous veno-venous hemodiafiltration(CVVHDF).Patients in the group B were firstly treated with CVVHDF followed by CVVH.Delivered doses of solutes with different molecular weights at the indicated time points between groups were compared.A correlation analysis between the delivered dose and pre-filter pressure(P_(PRE))and transmembrane pressure(P_(TM))was performed.Receiver operating characteristic(ROC)curves were constructed to evaluate the accuracy of P_(TM) as an indicator for filter replacement.RESULTS:A total of 50 cases were analyzed,27 in the group A and 23 in the group B.Delivered doses of different molecular-weight solutes significantly decreased before changing the filter in both modalities,compared with those at the initiation of treatment(all P<0.05).In the late stage of CRRT,the possible rebound of serum medium-molecular-weight solute concentration was observed.P_(TM) was negatively correlated with the delivered dose of medium-molecular-weight solute in both modalities.The threshold for predicting the rebound of serum concentration of medium-molecularweight solute by P_(TM) was 146.5 mm Hg(1 mm Hg=0.133 k Pa).CONCLUSIONS:The filter can be used as long as possible within the manufacturer’s safe use time limits to remove small-molecular-weight solutes.P_(TM) of 146.5 mm Hg may be an optimal indicator for changing the filter in CRRT therapies to remove medium-molecular-weight solutes.
基金supported by a grant from the Beijing Hope Run Special Fund(LC2011B38)
文摘BACKGROUND:Several risk scoures have been used in predicting acute kidney injury(AKI)of patients undergoing general or specific operations such as cardiac surgery.This study aimed to evaluate the use of two AKI risk scores in patients who underwent non-cardiac surgery but required intensive care.METHODS:The clinical data of patients who had been admitted to ICU during the first 24 hours of ICU stay between September 2009 and August 2010 at the Cancer Institute,Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively collected and analyzed.AKI was diagnosed based on the acute kidney injury network(AKIN) criteria.Two AKI risk scores were calculated:Kheterpal and Abelha factors.RESULTS:The incidence of AKI was 10.3%.Patients who developed AKI had a increased ICU mortality of 10.9%vs.1.0%and an in-hospital mortality of 13.0 vs.1.5%,compared with those without AKI.There was a significant difference between the classification of Kheterpal's AKI risk scores and the occurrence of AKI(P<0.001).There was no significant difference between the number of Abelha's AKI risk scores and the occurrence of AKI(P=0.499).Receiver operating characteristic curves demonstrated an area under the curve of 0.655±0.043(P=0.001,95%confidence interval:0.571-0.739) for Kheterpal's AKI risk score and 0.507±0.044(P=0.879,95%confidence interval:0.422-0.592) for Abelha's AKI risk score.CONCLUSION:Kheterpal's AKI risk scores are more accurate than Abelha's AKI risk scores in predicting the occurrence of AKI in patients undergoing non-cardiac surgery with moderate predictive capability.
基金supported by the Health Commission Clinical Characteristic Discipline Construction Program of Pudong New Area,Shanghai (PW Yts2021-17)Youth Science and Technology Project Health and Family Planning Commission of Pudong New Area,Shanghai (PWRq2020-35)。
文摘BACKGROUND:To determine the protective role of mesencephalic astrocyte-derived neurotrophic factor(MANF) in regulating sepsis-associated acute kidney injury(S-AKI).METHODS:A total of 96 mice were randomly divided into the control group,control+MANF group,S-AKI group,and S-AKI+MANF group.The S-AKI model was established by injecting lipopolysaccharide(LPS) at 10 mg/kg intraperitoneally.MANF(200 μg/kg) was administered to the control+MANF and S-AKI+MANF groups.An equal dose of normal saline was administered daily intraperitoneally in the control and S-AKI groups.Serum and kidney tissue samples were obtained for biochemical analysis.Western blotting was used to detect the protein expression of MANF in the kidney,and enzyme-linked immunosorbent assay(ELISA) was used to determine expression of MANF in the serum,pro-inflammatory cytokines(tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]).Serum creatinine(SCr),and blood urea nitrogen(BUN)were examined using an automatic biochemical analyzer.In addition,the kidney tissue was observed for pathological changes by hematoxylin-eosin staining.The comparison between two groups was performed by unpaired Student’s t-test,and statistics among multiple groups were carried out using Tukey’s post hoc test following one-way analysis of variance(ANOVA).A P-value <0.05 was considered statistically significant.RESULTS:At the early stage of S-AKI,MANF in the kidney tissue was up-regulated,but with the development of the disease,it was down-regulated.Renal function was worsened in the S-AKI group,and TNF-α and IL-6 were elevated.The administration of MANF significantly alleviated the elevated levels of SCr and BUN and inhibited the expression of TNF-α and IL-6 in the kidney.The pathological changes were more extensive in the S-AKI group than in the S-AKI+MANF group.CONCLUSION:MANF treatment may significantly alleviate renal injury,reduce the inflammatory response,and alleviate or reverse kidney tissue damage.MANF may have a protective effect on S-AKI,suggesting a potential treatment for S-AKI.
文摘Managing patients with heart failure （HF） is a challenging task within itself, but the presence of associated worsening renal function can greatly increase mortality and morbidity. Early diagnosis and treatment is the key to prevent re-hospitalizations and reduce healthcare costs. Biomarkers have long been established as highly sensitive and specific tools in diagnosing and prognosticating patients with HF. Reflecting distinct pathophysiological events and ongoing cellular insult, biomarkers have been proven superior to conventional laboratory tests. Availability of better assays and rapid analysis has allowed the use of biomarkers as point-of-care tests in the emergency department and at the patient＇s bed-side. Acute HF patients often go on to develop worsening renal function, termed as acute cardiorenal syndrome. The growing breadth of studies has shown the implications of combining multiple biomarkers to better chart outcomes and produce desirable results in such patients.
文摘Neurological complications after cardiac surgery, rang- ing from permanent stroke to transient dysfunction, repre- sent a key issue in the management of geriatric patients. Many patients aged 70 or more have history of neurological dysfunctions, which increases the risk of complications and sequelae, Severe neurologic diseases, such as strokes, occur in up to 6% of patients undergoing cardiac surgery. Therefore, in the setting of fragile patients, prevention is more important than treatment. There are several intraop- erative mechanisms of neurological injury, such as embo- lism, inflammation, intraoperative anemia,
基金supported by the Tianjin UniversityaDouble First Classoconstruction talent start-up fund to Dr.Yan-Hua Gong,the grants awarded to Shi-Ke Hou by Science and Technology Commission of the CMC(c12019048)Ning Li by Open Fund of State Key Laboratory of Medicinal Chemical Biology(Nankai University)(2020010)。
文摘Background:Acute kidney injury(AKI)is the main life-threatening complication of crush syndrome(CS),and myoglobin is accepted as the main pathogenic factor.The pattern recognition receptor retinoicacid-inducible gene I(RIG-I)has been reported to exert anti-viral effects function in the innate immune response.However,it is not clear whether RIG-I plays a role in CS-AKI.The present research was carried out to explore the role of RIG-I in CS-AKI.Methods:Sprague-Dawley rats were randomly divided into two groups:the sham and CS groups(n=12).After administration of anesthesia,the double hind limbs of rats in the CS group were put under a pressure of 3 kg for 16 h to mimic crush conditions.The rats in both groups were denied access to food and water.Rats were sacrificed at 12 h or 36 h after pressure was relieved.The successful establishment of the CS-AKI model was confirmed by serum biochemical analysis and renal histological examination.In addition,RNA sequencing was performed on rat kidney tissue to identify molecular pathways involved in CS-AKI.Furthermore,NRK-52 E cells were treated with 200μmol/L ferrous myoglobin to mimic CS-AKI at the cellular level.The cells and cell supernatant samples were collected at 6 h or 24 h.Small interfering RNAs(siRNA)was used to knock down RIG-I expression.The relative expression levels of molecules involved in the RIG-I pathway in rat kidney or cells samples were measured by quantitative real-time PCR(qPCR),Western blotting analysis,and immunohistochemistry(IHC)staining.Tumor necrosis factor-α(TNF-α)was d etected by ELISA.Co-immunoprecipitation(Co-IP)assays were used to detect the interaction between RIG-I and myoglobin.Results:RNA sequencing of CS-AKI rat kidney tissue revealed that the different expression of RIG-I signaling pathway.qPCR,Western blotting,and IHC assays showed that RIG-I,nuclear factor kappa-B(NF-κB)P65,p-P65,and the a poptotic marker caspase-3 and cleaved caspase-3 were up-regulated in the CS group(P<0.05).However,the levels of interferon regulatory factor 3(IRF3),p-IRF3 and the antiviral factor interferon-beta(IFN-β)showed no significant c hanges between the sham and CS groups.Co-IP assays showed the interaction between RIG-I and myoglobin in the kidneys of the CS group.Depletion of RIG-I could alleviate the myoglobin induced expression of apoptosis-associated molecules via the NF-κB/caspase-3 axis.C onclusions:RIG-I is a novel damage-associated molecular patterns(DAMPs)sensor for myoglobin and participates in the NF-κB/caspase-3 signaling pathway in CS-AKI.In the development of CS-AKI,specific intervention in the RIG-I p athway might be a potential therapeutic strategy for CS-AKI.
