Vancomycin associated acute kidney injury in patients with infectious endocarditis: a large retrospective cohort study.

Background: Vancomycin remains the cornerstone antibiotic for the treatment of infective endocarditis (IE). Vancomycin has been associated with significant nephrotoxicity. However, vancomycin associated acute kidney injury (AKI) has not been evaluated in patients with IE. We conducted this large retrospective cohort study to reveal the incidence, risk factors, and prognosis of vancomycin-associated acute kidney injury (VA-AKI) in patients with IE. Methods: Adult patients diagnosed with IE and receiving vancomycin were included. The primary outcome was VA-AKI. Results: In total, 435 of the 600 patients were enrolled. Of these, 73.6% were male, and the median age was 52 years. The incidence of VA-AKI was 17.01% (74). Only 37.2% (162) of the patients received therapeutic monitoring of vancomycin, and 30 (18.5%) patients had reached the target vancomycin trough concentration. Multiple logistic regression analysis revealed that body mass index [odds ratio (OR) 1.088, 95% CI 1.004, 1.179], duration of vancomycin therapy (OR 1.030, 95% CI 1.003, 1.058), preexisting chronic kidney disease (OR 2.291, 95% CI 1.018, 5.516), admission to the intensive care unit (OR 2.291, 95% CI 1.289, 3.963) and concomitant radiocontrast agents (OR 2.085, 95% CI 1.093, 3.978) were independent risk factors for VA-AKI. Vancomycin variety (Lai Kexin vs. Wen Kexin, OR 0.498, 95% CI 0.281, 0.885) were determined to be an independent protective factor for VI-AKI. Receiver operator characteristic curve analysis revealed that duration of therapy longer than 10.75 days was associated with a significantly increased risk of VA-AKI (HR 1.927). Kidney function was fully or partially recovered in 73.0% (54) of patients with VA-AKI. Conclusion: The incidence of VA-AKI in patients with IE was slightly higher than in general adult patients. Concomitant contrast agents were the most alarmingly nephrotoxic in patients with IE, adding a 2-fold risk of VA-AKI. In patients with IE, a course of vancomycin therapy longer than 10.75 days was associated with a significantly increased risk of AKI. Thus, closer monitoring of kidney function and vancomycin trough concentrations was recommended in patients with concurrent contrast or courses of vancomycin longer than 10.75 days.

Impact of pharmacist intervention in reducing vancomycin-associated acute kidney injury: A systematic review and meta-analysis.

AIMS: The aim was to quantify the relationship between pharmacist intervention and vancomycin-associated acute kidney injury (AKI). METHODS: Electronic databases were searched up to August 2020 for meta-analyses of cohort studies and/or randomized controlled trials. Studies that compared the incidence of AKI in patients between post- and prepharmacist intervention were investigated. The primary outcome was incidence of AKI. We also evaluated the influence of pharmacist intervention in risk factors of vancomycin-associated AKI. RESULTS: The search strategy retrieved 1744 studies and 34 studies with 19 298 participants were included (22 published articles and 12 abstracts from conference proceedings). Compared with the preintervention group, the postintervention group patients had a significantly lower incidence of vancomycin-associated AKI: 7.3% for post- and 9.6% for preintervention (odds ratio [OR] 0.52, 95% confidence interval [CI]; 0.41, 0.67], P < .00001). The rate of attaining target concentration was significantly higher in the post- than preintervention group (OR 2.86, 95% CI [2.23, 3.67], P < .00001). The postintervention group significantly improved the percentage of serum creatinine laboratory tests than preintervention group (OR = 3.24, 95% CI 2.02, 5.19], P < .00001). Patients postintervention had markedly lower risk of mortality than preintervention patients (OR 0.47, 95% CI [0.31, 0.72], P = .0004). CONCLUSION: Pharmacist intervention in vancomycin treatment significantly decreased the rate of vancomycin-associated AKI, while improving efficacy and reducing mortality. We speculate that this is because the pharmacist interventions optimized the rationality of vancomycin therapy, monitoring of vancomycin trough concentration and the monitoring of patients' renal function.

Vancomycin Associated Acute Kidney Injury: A Longitudinal Study in China.

Background: Vancomycin-associated acute kidney injury (VA-AKI) is a recognizable condition with known risk factors. However, the use of vancomycin in clinical practices in China is distinct from other countries. We conducted this longitudinal study to show the characteristics of VA-AKI and how to manage it in clinical practice. Patients and Methods: We included patients admitted to hospital, who received vancomycin therapy between January 1, 2016 and June 2019. VA-AKI was defined as a patient having developed AKI during vancomycin therapy or within 48 h following the withdrawal of vancomycin therapy. Results: A total of 3719 patients from 7058 possible participants were included in the study. 998 patients were excluded because of lacking of serum creatinine measurement. The incidence of VA-AKI was 14.3%. Only 32.3% (963/2990) of recommended patients performed therapeutic drug monitoring of vancomycin. Patients with VA-AKI were more likely to concomitant administration of cephalosporin (OR 1.55, 95% CI 1.08-2.21, p = 0.017), carbapenems (OR 1.46, 95% CI 1.11-1.91, p = 0.006) and piperacillin-tazobactam (OR 3.12, 95% CI 1.50-6.49, p = 0.002). Full renal recovery (OR 0.208, p = 0.005) was independent protective factors for mortality. Compared with acute kidney injury stage 1, AKI stage 2 (OR 2.174, p = 0.005) and AKI stage 3 (OR 2.210, p = 0.005) were independent risk factors for fail to full renal recovery. Conclusion: Lack of a serum creatinine measurement for the diagnosis of AKI and lack of standardization of vancomycin therapeutic drug monitoring should be improved. Patient concomitant with piperacillin-tazobactam are at higher risk. Full renal recovery was associated with a significantly reduced morality.

The difference of T cell phenotypes in end stage renal disease patients under different dialysis modality.

BACKGROUND: Impaired T cell immune function exists in end-stage renal disease (ESRD) patients. Dialysis treatment may lead to changes in T cell subsets. In the present study, we aimed to identify alterations of T cell phenotypes in ESRD patients, especially in those receiving peritoneal dialysis (PD), and analyze the potential associated factors. METHODS: In the present study, 110 PD patients and 110 age/gender-matched hemodialysis (HD) patients who met the inclusion criteria were studied. Pre-dialysis blood samples were obtained and analyzed by flow cytometry to detect the expression of CD45RO and CCR7. Univariate and multivariate regression analyses were used to determine the factors associated with the alteration of T cell phenotypes. RESULTS: In all dialysis patients, age was associated with the frequencies of both CD4+ and CD8+ naïve T cells, effector memory (EM) T cells and effector memory RA (EMRA) T cells but not central memory (CM) T cells. Dialysis modality was also associated with T cell subsets. Compared with HD patients, PD patients showed an increase in both CD4+ and CD8+ CM T cells and a reduction in both CD4+ and CD8+ EM and EMRA T cells. However, the number of CD4+ naïve T cells was lower and the number of CD8+ naïve T cells was higher in PD patients than those in HD patients. In PD patients, further multivariate analysis revealed that the frequency of CD4+ naïve T cells was positively associated with nPCR, while the frequency of CD8+ naïve T cells was negatively associated with age. CONCLUSION: In dialysis patients, the dialysis modality and age influence T cell subsets. There is a progression from naïve to effector T cells in HD patients compared with PD patients. In PD patients, different factors may influence the frequencies of CD4+ and CD8+ naïve T cells.

Elevated serum soluble interleukin-2 receptor levels increase malignancy-related risk in patients on chronic hemodialysis.

BACKGROUND: Patients on chronic hemodialysis (HD) have an increased incidence of malignancy due to decreased immunity. Soluble interleukin-2 receptor (sIL-2R), as an immunomodulator, seemed to have an effect in the process of malignancy. In this study, we aimed to evaluate the clinical significance of increased sIL-2R in the course of malignancy among HD patients. METHODS: Patients who undergoing chronic hemodialysis were followed for 24 months. Risk factors for malignancy events and malignancy-related mortality during the 2-year follow-up period were investigated among various clinicopathological variables. RESULTS: Of the 363 patients included in this research, 47 patients (12.95%) had a prior history of treated malignancy. During the 2-year follow-up period, malignancy events were detected in 15 (4.12%) patients. Sixty-seven patients died during the study period, of which nine patients (13.43%) were died of malignancy. Malignancy events reduced 2-year mortality significantly (log-rank = 23.02, P < 0.0001). Both high sIL-2R levels ( ≥ 2-fold upper limit of the normal value) (OR 6.6, P = 0.006) and a prior history of treated malignancy (OR 4.12, P = 0.018)were identified by multivariate logistic analysis as independent determinants for malignancy events. However, only the levels of sIL-2R (used as a continuous variable) had the significantly predictive effect on malignancy events and malignancy-related mortality in the following 2 years. CONCLUSIONS: Elevated sIL-2R levels was commonly seen in serum of HD patients. And this elevated level increased the risk of malignancy. Aside from its role as a biomarker, sIL-2R may also exert biological effects in the course of malignancy.

Role of body mass index on acute kidney injury patients after cardiac surgery / 中华肾脏病杂志

Objective To explore the association between BMI and the risk of developing cardiac surgery associated acute kidney injury (CS-AKI),mortality of AKI and AKI requiring renal replacement therapy (AKI-RRT) after cardiac surgery.Methods Clinical data of patients undergoing cardiac surgery from January 2011 to December 2015 in Zhongshan Hospital of Fudan University were prospectively collected.Patients were divided into four groups according to BMI classification of Chinese population.Adjustment for selection bias was further assessed using propensity score method (PSM) to evaluate the role of BMI in the development of AKI.Results A total of 8442 patients were enrolled,among which 1092 patients successfully matched through PSM.The AKI incidences were respectively 30.3％,33.3％,38.6％ and 46.8％ in four BMI groups (P ＜ 0.01) before PSM.The AKI incidences were respectively 31.9％,35.2％,42.5％ and 42.9％ in four BMI groups (P=0.016) after PSM.The risk of developing AKI increased by 19.9％ as the BMI increased per 5 kg/m2 (95％ CI:1.070-1.344,P=0.002).The hospital mortality of patient (overall,AKI,AKI-RRT) in four groups was not statistically different after PSM (P ＞ 0.05),but overweight group always had the lowest mortality.Conclusions BMI is a risk factor for AKI after cardiac surgery,and the AKI incidence increases with increasing BMI in a certain range.

Primary study of chronic kidney disease with intravoxel incoherent motion diffusion-weighted imaging / 中华放射学杂志

Objective To investigate the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the staging of chronic kidney disease(CKD).Methods From May 2016 to April 2017,seventy-two patients diagnosed as CKD according to the criteria of clinical diagnostic and 20 healthy volunteers (control group) underwent routine MRI and IVIM-DWI ( 8 b values, 0 to 800 s/mm2).CKD patients were divided into two groups based on their estimated glomerular filtration rate (eGFR): mild CKD group(45 cases,eGFR≥60 ml·min-1·1.73m-2)and moderate to severe CKD group(27 cases,eGFR<60 ml·min-1·1.73 m-2).The ADC,true diffusion coefficient(D),pseudo-diffusion coefficient(D*),perfusion fraction (f) were measured on both cortex and medulla. The paired-samples t test was used to compare the cortico-medullary difference of the ADC,D,D*and f values in three groups.Differences of the ADC,D, D*and f values among three groups were compared using the one-way analysis of variance (ANOVA). Correlations between eGFR and the IVIM-DWI parameters in CKD were evaluated by using Pearson correlation analysis. ROC was performed to evaluate the diagnostic efficiency of using IVIM-DWI parameters to distinguish CKD with moderate to severe renal impairment from mild renal impairment, as well as distinguish CKD with mild renal impairment from healthy volunteers.Results The cortical ADC,D, D*and f values were significantly higher than that in the medulla in healthy volunteers(all P<0.05). The cortical ADC,D*and f values were significantly higher than that in the medulla in mild CKD group(all P<0.05). The cortical ADC,D and f values were significantly higher than that in the medulla in moderate to severe CKD group (all P<0.05). The ADC,D,D*and f values of cortex and medulla showed significantly differences among three groups(all P<0.05).In CKD patients,no significant correlation was found between medullary D*,f values and eGFR, there was a significant positive correlation between eGFR and cortical ADC,D,D*and f values(r=0.475,0.362,0.625,0.276;all P<0.05),as well as between eGFR and medullary ADC,D values(r=0.427,0.615;P<0.05). The results of the ROC analysis for distinguishing the mild CKD group from the moderate to severe CKD group revealed that the cortical D*value had the highest area under the ROC curve (AUC=0.965), cortical f value showed high sensitivity(92.6%) to distinguish CKD with different degree of renal impairment, with the threshold of 32.99%, and cortical D*value showed high specificity(97.8%)with the threshold of 17.07×10-3mm2/s;the results of the ROC analysis for distinguishing the mild CKD group from healthy volunteers revealed that the cortical D*value had the highest AUC(0.885), medullary ADC value showed high sensitivity (82.2%) to distinguish mild CKD group from healthy volunteers,with the threshold of 1.83×10-3mm2/s,and medullary f value showed high specificity(100.0%)with the threshold of 21.70%,as well as medullary D value showed high specificity(100.0%)with the threshold of 1.75× 10-3mm2/s.Conclusion IVIM-DWI may be useful for CKD early diagnosis and assessing renal function.

The pulmonary arterial hypertension of patients on maintained hemodialysis is positively associated with the decreased percent of CD8 T cell in the peripheral blood independently / 中华肾脏病杂志

Objective To explore the risk factors of pulmonary artery hypertension (PAH) and the its relationship with T cell subsets to provide a foundation for the prevention and treatment of PAH.Methods 154 maintained hemodialysis (MHD) patients in our dialysis center were recruited according to the criterion and divided into two groups subsequently:PAH group (pulmonary artery systolic pressure,PASP ＞ 35 mmHg) and non-PAH group (PASP≤35 mmHg).The related clinical,biochemical and ultrasonic cardiogram data were collected and peripheral blood was acquired to detect the expressions of the surface antigen CD3,CD4,CD8 and CD69 with flow cytometry.Logistic regression analysis was used to find out the relationship between PAH and T cell subsets.Results There was no significant difference between 56 cases of PAH and 98 cases of non-PAH as regards gender,age,mean systolic and diastolic pressure,dialysis durations,morbidities of hypertension and diabetes,smoking rate,and left ventricular diameter.Compared with the non-PAH group,the PAH group demonstrated a lower percent of CD8 T cells and CD8 CD69 T cells,but a much higher left atrial diameter (LAD),Interventricular septum thickness,left ventricular posterior wall thickness,and NT-proBNP.The percentage of T cells,CD4 T cells and CD4 CD69 T cells showed no difference between the two groups.Multivariate analysis confirmed that PAH was negatively independently associated with the percentage of CD8 T cells and CD8CD69 T cells.Conclusions The decreased percentage of CD8 T cells and CD8CD69 T cells in the peripheral blood is a risk factor of PAH in maintained hemodialysis patients,and CD8 T cells may play an important role in the genesis of PAH.

Epidemiological features and therapeutic effect of 183 adults with idiopathic membranous nephropathy / 中华肾脏病杂志

Objective To retrospectively analyze the clinical epidemiology features of adult idiopathic membranous nephropathy (IMN) in Zhongshan Hospital,and to investigate their therapeutic effect and its possible influence factors.Methods A total of 183 patients admitted to the Zhongshan Hospital of Fudan University and diagnosed as IMN by renal biopsy from January 2013 to December 2015 were involved.Their baseline information including demographics and pathologic was collected.Patients were followed up for at least 12 months.Serum albumin ＜ 30 g/L and 24 h urine protein ＞ 3.5g were defined as nephrotic syndrome (NS).IMN patients were divided into NS and non-NS groups and compared.Furthermore,the baseline data of remission and no remission patients were compared,and the correlations of their baseline data with conservative and immunosuppressive therapy were assessed by logistic regression analysis.Results (1) IMN accounted for 11.1％ of renal biopsy cases in our hospital,with an average age of 57 years and 59.6％ male patients.(2) Compared with patients without NS,IMN patients with NS were older,had a shorter time from the onset to receive renal biopsy,lower estimated glomerular filtration rate,and higher total cholesterol,low density lipoprotein cholesterol,triglyceride and serum creatinine (all P ＜ 0.05).(3) The effective rate of conservative treatment in IMN patients without NS was 65.7％,and the ineffective group had higher triglyceride compared with the effective group (P=0.019).(4) The effective rate of immunosuppressive therapy in IMN patients with NS was 81.2％,and low serum albumin was an independent risk factor for the poor efficacy of immunosuppressive therapy (OR=1.202,95％ CI 1.003-1.440,P=0.046).(5) The effective rate of conservative treatment in IMN patients with NS was 55.5％,and low serum albumin was an independent risk factor for the poor efficacy of conservative treatment (OR=1.629,95％CI 1.047-2.536,P=0.023).Conclusions The detection rate of IMN is increasing year by year,but the remission rate of conservative treatment is still not low in mild and moderate patients.For the patients without NS,high triglyceride may predict a poor effect of conservative treatment.Hypoproteinemia is a predictor of poor effect,no matter what a NS patient takes immunosuppressive therapy or conservative treatment.

Salvianolic Acid B Prevents Iodinated Contrast Media-Induced Acute Renal Injury in Rats via the PI3K/Akt/Nrf2 Pathway.

Contrast-induced acute renal injury (CI-AKI) has become a common cause of hospital-acquired renal failure. However, the development of prophylaxis strategies and approved therapies for CI-AKI is limited. Salvianolic acid B (SB) can treat cardiovascular-related diseases. The aim of the present study was to assess the effect of SB on prevention of CI-AKI and explore its underlying mechanisms. We examined its effectiveness of preventing renal injury in a novel CI-AKI rat model. Compared with saline, intravenous SB pretreatment significantly attenuated elevations in serum creatinine and the histological changes of renal tubular injuries, reduced the number of apoptosis-positive tubular cells, activated Nrf2, and lowered the levels of renal oxidative stress induced by iodinated contrast media. The above renoprotection of SB was abolished by the PI3K inhibitor (wortmannin). In HK-2 cells, SB activated Nrf2 and decreased the levels of oxidative stress induced by hydrogen peroxide and subsequently improved cell viability. The above cytoprotection of SB was blocked by the PI3K inhibitor (wortmannin) or siNrf2. Thus, our results demonstrate that, due to its antioxidant properties, SB has the potential to effectively prevent CI-AKI via the PI3K/Akt/Nrf2 pathway.

Association of intradialytic hypotension and 5-year mortality in maintaining hemodialysis patients / 中华肾脏病杂志

Objective To assess the risk factors of intradialytic-hypotension (IDH) and the prognosis of IDH among maintenance hemodialysis (MHD) patients for the prevention and treatment of IDH.Methods 276 MHD patients were enrolled during Jan.2009 to Mar.2009.Intradialytic blood pressure was monitored during a 3-month period.IDH was defined as an event characterized by a sudden drop in systolic BP more than 20 mmHg or in mean artery pressure (MAP) more than 10 mmHgassociated with clinical events and need for interventions.Dialysis-related information was collected.Kaplan-Meier method,log-rank test,logistic regression and Cox regression analyses were performed to examine the association between IDH and survival,using a follow-up through 31 May 2014.Results A total of 276 patients were recruited.The incidence rate of IDH was 40.9％.163 patients with no-IDH (＜ 1/10 hypotensive events/3 months) served as controls.113 patients with IDH (≥ 1/10 hypotensive events/3 months) were identified among all 276 patients.Multivariate logistic regression analysis showed that age,ultrafiltration rate,gender,serum NT-proBNP,serum albumin and aortic rool inside dimension (AoRD) were associated with IDH among MHD patients.During the 5-year follow-up,74 patients died,with a mortality rate 5.2 per 100 person-year.Kaplan-Meier survival curve showed significant difference of overall and CV mortality rates between 2 groups.The multivariate Cox regression model indicated that IDH increased the risk of death (HR=1.572,95％CI 1.077-2.293,P=0.019).So did the rise of LVMI (HR=1.010,95％CI 1.009-1.085,P=0.020).Conclusion Elderly,female,high ultrafiltration rate,high level of serum NT-proBNP,hypoalbuminemia and shorter AoRD are independent risk factors for IDH among MHD patients.LVMI can predict the outcome of MHDpatients.Intradialytic hypotension is an independent risk factor for long-term mortality in MHD patients.

Sustained increase of microRNA-21 abundance drives aristolochic acid-induced acute kidney injury to renal tubulointerstitial fibrosis / 中华肾脏病杂志

Objective To investigate the role of increased microRNA-21 (miR-21) in the development of renal tubulointerstitial fibrosis secondary to aristolochic acid induced acute kidney injury.Methods C57BL/6J male mice were intraperitoneally injected with aristolochic acid at a dose of 10 mg/kg.Blood samples and kidneys were harvested at day 1,3,7,14,28 after aristolochic acid treatment.To assess the role of miR-21 in aristolochic acid induced acute kidney injury to chronic kidney disease progression,mice were intravenously injected with anti-miR-21 or anti-scramble (10 mg/kg) at 1 h before aristolochic acid dosing,as well as d5 and d10 after aristolochic acid dosing.Results Increased serum creatinine and severe kidney injury were found at d3 after aristolochic acid treatment.Renal tubulointerstitial fibrosis was developed at d14 after aristolochic acid treatment.Protein expression of α-SMA,vimentin and collagen Ⅰ were significantly up-regulated at d7 and peaked at d14 (P ＜ 0.01),while protein abundance of E-Cadherin decreased at d14 and lasted until d28 (P ＜ 0.01).The abundance of miR-21 increased at d7 after aristolochic acid dosing,peaking at d14 and thereafter maintaining at a high level.Anti-miR-21 intervention relieved renal injury with reduced serum creatinine (P ＜ 0.05) and attenuation of renal tubulointerstitial fibrosis.Besides,the protein expression of α-SMA,vimentin,and collagen Ⅰ/Ⅳ was all down-regulated after anti-miR-21 treatment (P ＜ 0.05).PTEN was up-regulated and the ratio of its downstream genes p-AKT/AKT was decreased.(P ＜ 0.05) Conclusions A single high dose of aristolochic acid leads to acute kidney injury and the development of renal tubulointerstitial fibrosis secondary to AKI.Renal tubulointerstitial fibrosis could be partially reversed by inhibiting miR-21 via PTEN/p-AKT pathway.

Role of prolyl hydroxylases 2 in the cellular response to hypoxia activated autophagy in human renal epithelial cell model / 中华肾脏病杂志

Objective To test the hypothesis of autophagy that silencing PHD2 gene could increase hypoxia inducible factor (HIF)-1α levels in the renal medulla and attenuate hypoxia injury in cultured human renal proximal tubular epithelial cell (HK-2) under cobalt dichloride (CoCl2) exposure.Methods HK-2 cells were harvested at hour 0,6,12,24,36 and 48 after exposure to CoC12 (200 μmol/L).The role of HIF/PHD pathway in CoCl2-induced cell apoptosis/autophagy was studied by employing small-interfering RNA (siRNA).Dynamic profiles of apoptosis markers (Bax,Bcl-xl) and autophagy marker (LC3) of HK-2 cells within 48 h after exposing to CoCl2 were recorded.Alamar Blue assay was used for quantitative analysis of cellular growth and viability.Electron microscopy analysis was employed to evaluate the changes in autophagic structures.Results The protein expressions of PHD2 were gradually increased after exposing to CoCl2 (200 μmol/L),with statistics significance at 24 h and reached the peak at 48 h (both P ＜ 0.01).PHD2 siRNA reduced PHD2 levels by ＞ 60％ and significantly increased HIF-1α protein levels (P ＜ 0.01),but had little effect on HIF-2α.The protein expression of Bcl-xl was significantly up-regulated,while the level of Bax and LC3-Ⅱ/LC3-Ⅰ were down-regulated in PHD2 siRNA group (all P ＜ 0.01),compared with the negative control group.Meanwhile,either 3-Methyladenine (an autophagy inhibitor) treatment or PHD2 knockdown rescued cell death and increased cell viability through autophagy inactivation.The ratio of LC3-Ⅱ/LC3-Ⅰ and the quantity of autophagosomes were decreased,and the cell ultrastructure was also relatively intacter than the negative control group.Of interest,co-administration of HIF-1α siRNA with PHD2 siRNA abrogated renoprotective effect conveyed by PHD2 siRNA alone,suggesting that activation of endogenous HIF-1α-dependent pathways mediated the autophagy inactivation effects of PHD2 silencing.Conclusions Direct inhibition of PHD2 promotes renal epithelia cell survival against CoCl2-induced cell apoptosis/autophagy.Activation of the HIF-1α signaling pathway is required to reduce apoptosis and autophagy via up-regulating the expression of Bcl-xl protein.

Molecular mechanism of miR-382 in the pathogenesis of renal tubulointerstitial fibrosis / 中华肾脏病杂志

Objective To investigate the roles of microRNA-382 (miR-382) in the pathogenesis of renal tubulointerstitial fibrosis (TIF).Methods Human kidney epithelial cells (HK2)transfected with miR-382 inhibitor (antagomiR-382) were used to examine the effect of miR-382 abundance on cell polarity,as well as to test the complementary relationship between miR-382 and its predicted target gene heat shock protein 60 (HSPD1),which was further verified by 3'-untranslated region luciferase assay and site-directed mutagenesis.The role of miR-382 played in the development of renal interstitial fibrosis and redox regulation was examined in a mouse unilateral ureteral obstruction (UUO) model.Locked nucleic acid (LAN)-modified anti-miR-382 was intravenous delivered via tail vein 30 min prior to UUO,and repeated the dosage 24 h after the surgery.For clinical verification,renal biopsy specimens from 12 IgA nephropathy (IgAN) patients were collected,6 patients with moderate to severe TIF and 6 patients without TIF.The relative abundance of miR-382 and HSPD1 protein was analyzed by using in situ hybridization and immunohistochemistry.Results HSPD1 was confirmed to be a new,direct target gene of miR-382 by in vitro 3'-untranslated region luciferase assay and sitedirected mutagenesis.The development of epithelial transition in HK2 cells was accompanied with upregulation of miR-382 [(6.54±0.96) vs (1.12±0.26),P ＜ 0.05].Blocking the expression of miR-382 could reversed the progression of epithelial transition partially.In UUO mice the abundance of miR-382 was up-regulated [(6.89 ± 2.47) vs (1.00±0.42),P ＜ 0.01] while HSPD1 and Trx were downregulated compared with the sham group.Down-regulation of miR-382 was associated with significant decrease in TIF,but increase in HSPD1 and thioredoxin protein compared with UUO group [HSPD1:(0.34±0.10) vs (0.14±0.05);Trx:(0.79±0.18) vs (0.36±0.16);all P ＜ 0.05].The expression of miR-382 was up-regulated and HSPD1 was significantly down-regulated in IgAN patients with TIF.Conclusions miR-382 play an important role in renal tubulointerstitial fibrosis in human and mice.HSPD1 is one of the target genes of miR-382.The down-regulation of HSPD1 and the decrease ability of anti-oxidative stress may be the important mechanism of miR-382 involved in renal tubulointerstitial fibrosis.

Mechanism of miR?21 in delayed ischemia preconditioning and its protection against subsequent ischemia reperfusion injury in kidney / 中华肾脏病杂志

Objective To investigate the molecular mechanism of protection of ischemia preconditioning on renal ischemia reperfusion injury. Methods Male C57/BL6N mice were randomly divided into two groups: in IR group, 35 min ischemia was induced by occlusion of both renal pedicles followed by 24 h perfusion (I/R). 15 min ischemia was induced 4 days before I/R in IPC group. Blood sample and kidney were collected in IR and IPC group after 24 h perfusion. Serum creatinine (Scr) and histological changes were used to evaluate the renal injury. PHD2 and HIF-1αwere evaluated by Western blotting, miR-21 expression was confirmed by real-time PCR. In vitro, hypoxic model was established by 1% O2 in HK-2 cells. Knockdown of miR-21 in hypoxic model was perfermed by locked nucleic acid modified-anti-miR-21 transfection. The levels of miR-21, HIF-1α and PHD2 mRNA were confirmed by real-time PCR. The levels of HIF-1α and PHD2 proteins were tested by Western blotting. Results In vivo, Compared with IR group, the renal function and histological changes were improved in IPC group (P<0.01). Compared with IR group, the expression of miR-21(P<0.01) and HIF-1α(P<0.05) were increased in IPC group, while PHD2 was reduced (P<0.01). In vitro, hypoxia reduced miR-21. The inhibition of miR-21 could increased the expression of PHD2 (P<0.05). Conclusions Ischemia preconditioning may exert protection against renal ischemia reperfusion injury by inhibiting PHD2.

A long-term outcome study of acute kidney injury after cardiac surgery / 中华内科杂志

Objective To evaluate the long-term outcome of acute kidney injury (AKI) during hospitalization after cardiac surgery.Methods 1 770 patients underwent cardiac surgery in Fudan University Zhongshan Hospital from April 2009 to February 2011 were enrolled.Based on the Kidney Disease:Improving Global Outcomes (KDIGO) guideline of AKI,the patients were divided into the AKI and the nonAKI groups,and followed up for 2 years.The 2-year survival rate and incidence of the advanced chronic kidney disease (CKD) was compared between the two groups.Factors influencing the 2-year survival rate and incidence of the advanced CKD were also analyzed.Results Among all the patients,715 (40.4％) of them were developed AKT.(1) The 2-year survival rate of the AKI group was lower than that of the non-AKI group (83.2％ vs 93.6％ ;P ＜0.05).Compared with the non-AKI group,AKI group had an increased risk for death with the hazard ratio of 1.710 (95％ CI 1.250-2.340).COX regression analysis showed that AKI was an independent factor for death with the risk intensity just less than diabetes and chronic cardiac insufficiency.The advanced age,the preoperative history of chronic cardiac insufficiency and the time of staying in ICU also significantly increased the risk of death.(2) Compared with patients without AKI (0.2 ％),the incidence of the 2-year of advanced CKD was higher in patients with AKI (6.7 ％ ; P ＜ 0.05) with an hazard ratio of 31.220 (95 ％ CI 7.550-129.110).COX regression analysis showed that AKI was still the independent risk factor for advanced CKD after adjustment of other factors.In addition,diabetes,the time of the cardiopulmonary bypass and the time of staying in ICU were also associated with the risk for the advanced CKD.Conclusions AKI is common after cardiac surgery,which was associated with a decrease in the 2-year survival rate and an increase in the incidence of advanced CKD of patients,which emphasized the importance of prevention and treatment of AKI,and close follow-up of renal function for the improvement of patient long-term prognosis.

Validation of 5 prediction models for acute kidney injury and its outcome after cardiac surgery procedures in Chinese patients / 中华肾脏病杂志

Objective To assess the clinical usefulness and value of the 5 models for the prediction of acute kidney injury (AKI),severe AKI which renal replacement treatment was needed (RRT-AKI) and death after cardiac surgery procedures in Chinese patients.Methods One thousand and sixty-seven patients who underwent cardiac surgery procedures in the department of cardiac surgery in the Zhongshan Hospital,Fudan University between May 2010 and January 2011 were involved in this research.The predicting value for AKI (AKICS),RRT-AKI (Cleveland,SRI and Mehta score) and death (EURO score) after cardiac surgery procedures was evaluated by Hosmer-Lemeshow goodness-of-fit test for the calibration and area under receiver operation characteristic curve (AUROC)for the discrimination.Results The incidence of AKI was 20.34％(217/1067),and 63.13％ of their renal function recovered completely.The incidence of RRT-AKI was 3.56％(38/1067) and the mortality of AKI and RRT-AKI was 9.68％ (21/217) and 44.73％ (17/38) respectively.The total mortality was 3.28％ (35/1067).The discrimination and calibration for the prediction ofAKI of AKICS were low.For the prediction ofRRT-AKI,the discrimination and calibration of Cleveland score were high enough,but the predicated value was lower than the real value (1.70％ vs 3.86％).The discrimination of Mehta score and the calibration of SRI were low.The discrimination and calibration for the prediction of death of EURO score was low.Conclusion According to the 2012 KDIGO AKI definition,none of the 5 models above is good at predicting AKI after cardiac surgery procedures.Cleveland score has been validated to have a proper impact on predicting RRT-AKI after cardiac surgery procedures,but the predicting value is still in doubt.EURO score has been validated to have an inaccurate predicting value for death after cardiac surgery procedures.

Decreased lymphocyte and increased monocyte count in peripheral blood is associated with cardiovascular disease and one-year mortality in maintenance hemodialysis patients / 中华肾脏病杂志

Objective To investigate the association between peripheral white blood cell count including its subtypes and cardiovascular disease (CVD) incidence and one-year all-cause mortality in maintenance hemodialysis (MHD) patients.Methods A total of 371 MHD patients at Zhongshan Hospital,Fudan University between March 2009 and February,2011 were enrolled.Demographic,hematological,nutritional and inflammatory markers were obtained.All patients were followed for one year to investigate the risks for CVD event and mortality.Spearman correlation and linear regression were used to assess the relationship between white blood cell count and other laboratory parameters.Difference in categorical factors between two groups were determined with Chi-square test,Difference in continuous values between two groups were assessed with t test.Kaplan-Meier analysis and Cox proportional hazards model were applied to assess one-year mortality predictors.Results Patients with CVD event had lower lymphocyte count level (1.17±0.38 vs 1.34±0.51,P＜ 0.05) and higher monocyte count level (0.44 ± 0.15 vs 0.37 ± 0.15,P＜0.01) than those without CVD event.Cox proportional hazard regression showed that an increased lymphocyte count was associated with reduced mortality risk,95％CI:0.136-0.719,P ＜ 0.01) and that an increased monocyte count was associated with increased mortality risk,95％ CI:2.657-74.396,P＜0.01) after adjustment for hsCRP.Conclusion Decreased lymphocyte level and increased monocyte level are significantly related to CVD event and are independent predictors of increased one-year all-cause mortality risk in MHD patients.

The risk factors and prognosis of acute kidney injury after cardiac surgery: a prospective cohort study of 4007 cases / 中华内科杂志

Objective To investigate the risk factors and prognosis influential factors of acute kidney injury (AKI) after cardiac surgery.Methods The clinical data of patients who were hospitalized and underwent cardiac surgery from April 2009 to May 2011 were collected prospectively.Demographic characteristics,types of surgeries,preoperative renal function,pre-and intra-operative conditions and clinical outcomes,etc were recorded.Results A total of 4007 patients underwent cardiac surgery were recruited.The overall incidence of AKI was 31.2％ (1250/4007).The incidence of AKI requiring renal replacement treatment (AKI-RRT) was 2.6％ (104/4007).The overall hospital mortality was 1.9％ (77/4007),and was significantly higher in AKI group than in non-AKI group (5.4％ vs 0.3％,P ＜0.01).The hospital mortality of AKI-RRT group was 36.5％ (38/104).Grouped by type of surgery,cardiac transplantation had the highest AKI incidence (73.0％) and highest in-hospital mortality (18.9％),followed by coronary artery bypass grafting (CABG) combined with valve surgery (AKI incidence 57.8％,in-hospital mortality 6.1％) and aneurysm surgery (AKI incidence 52.0％,in-hospital mortality 5.5％).Multivariate logistic regression analysis showed that man,age,BMI,hypertension,chronic heart failure,pre-operative serum creatinine (SCr) ＞ 106.0 μmol/L,intra-operative cardiopulmonary bypass time,intra-operative hypotension and aneurysm surgery were the risk factors of AKI after cardiac surgery.Multivariate logistic regression analysis showed that pre-operative SCr ＞ 106.0 μmol/L and intra-operative hypotension were independent risk factors of renal recovery after cardiac surgery while recovery of urine output was the favorable factor.Conclusions Cardiac surgery usually induces high AKI incidence and poor prognosis,which closely associated with many risk factors in peri-operative stage.The incidence of AKI is related to a number of perioperative risk factors.Heart transplantation,aneurysm surgery,CABG combined valve surgery are high risk surgeries.

NT-proBNP as a predictor of intradialytic-hypotension among maintaining hemodialysis patients / 中华肾脏病杂志

Objective To assess the risk factors of intradialytic-hypotension (IDH) among maintaining hemodialysis (MHD) patients and to explore the relation between NT-proBNP and IDH,thus to provide clinical evidence for the prevention and treatment of IDH.Methods A total of 202 MHD patients during March 2009 to May 2009 in our dialysis center were enrolled in the study.Intradialytic blood pressure (BP) was measured during a 3-month period.IDH was defined as an event characterized by a sudden drop in systolic BP more than 20 mm Hg or in mean artery pressure (MAP) more than l0 mm Hg.Logistic regression analysis was used to assess the risk factors of IDH.ROC curve was used to evaluate the diagnostic efficacy of serum NT-proBNP.Results The incidence of IDH was 42.1％.One hundred and seventeen patients with no-IDH (＜1/10 hypotensive events per 3 months) were served as controls.Fifty-five patients with o-IDH (≥ 1/ 10 but ≤1/3 hypotensive events per 3 months) and 30 patients with f-IDH (＞1/3 hypotensive events per 3 months) were identified among 202 patients.Multivariate regression analysis showed that age,gender,ultrafiltration rate,serum NT-proBNP,serum albumin,aortic root dimension (AoRD) were associated with IDH among MHD patients.Serum NT-proBNP was positively correlated with IDH.The area under the ROC curve (AUC) of NT-proBNP was 0.76 (95％ CI 0.69 to 0.83,P＜0.01).The cut-off value of serum NT-proBNP for IDH was 1746.5 ng/L,with a sensitivity of 88.61％ and a specificity of 51.10％.Furthermore,the AUC of NT-proBNP for f-IDH was 0.65 (95％ CI 0.53 to 0.763,P＜0.01).The cut-off value of serum NT-proBNP for f-IDH was 8208.0 ng/L,with a sensitivity of 33.33％ and a specificity of 91.30％.Conclusions Elderly,female,high ultrafiltration rate,high level of serum NT-proBNP,hypoalbuminemia,shorter AoRD are independent risk factors of IDH among MHD patients.Serum NT-proBNP can be used as a predictor of IDH.