1.Low-density lipoprotein promotes epithelial-mesenchymal transition and extracellular matrix accumulation in human peritoneal mesothelial cells
Yanhui FANG ; Lanping JIANG ; Limeng CHEN ; Xuemei LI ; Xuewang LI
Chinese Journal of Nephrology 2013;(1):44-49
Objective To investingate the effect of low-density lipoprotein (LDL) on epithelial -mesenchymal transition and extracellular matrix (ECM) accumulation in human peritoneal mesothelial cells (HPMCs).Methods (1)HPMCs were randomly divided into control group,LDL group (100 mg/L) and LDL (100 mg/L) + lactoferrin (100 mg/L,LDL receptor blocking agent) group.After co-cultured for 24 h,the expression of LDL receptor in HPMCs was examined by immunofluorescence staining,and the LDL uptake by HPMCs was observed with oil red O staining.(2)HPMCs were cultured with different concentrations of LDL (0,25,50,100 mg/L).After co-cultured for 24 h,the change of cell morphology was observed by inverted phase contrast microscope,and the expression of α-smooth muscle actin (α-SMA) was examined by immunofluorescence.(3) HPMCs were randomly divided into control group (5.6 mmol/L glucose),mannitol group (M,2.18% mannitol),low glucose group (LG,30 mmol/L),high glucose group (HG,120 mmol/L) and HG + LDL group (120 mmol/L glucose + 100 mg/L LDL).Cocultured for 48 h,the mRNA expression of α-SMA,E-cadherin and type 1 plasminogen activator inhibitor (PAI-1) was detected by real-time quantitative PCR,the protein expression of α-SMA was detected by Western blotting,the content of type I collagen (Col I) and PAI-1 in supernatant was detected by ELISA.Results (1) After co-cultured with LDL for 24 h,the expressin of LDL receptor was found on the cell membrane of HPMCs.Oil red staining showed that LDL could be uptaken into the cells and abolished by LDL receptor blocker.(2) HPMCs tended to be loosely intercellular connected to each ofher,and prsesnted significant formation of fibroblast-like spindle morphology.The cytoplasm immunofluorescence intensity of α-SMA gradually increased with the increase of LDL concentration.Compared to the control group,the expressions of α-SMA mRNA and protein were significantly increased,and the expression of E-cadherin mRNA was decreased in HG + LDL group(all P < 0.05).But the expressions of the parameters above-mentioned were not significant different between HG group and HG + LDL group or between HG group and control group.(3) Compared with HG group or control group,the concentrations of Col Ⅰ [(19.27±0.17) μg/L vs (14.09±0.30) μg/L or (14.81±0.91) μg/L,all P < 0.05] and PAI-1 [(498.24±76.91) ng/L vs (342.19±30.43) ng/L or (220.39±33.82) ng/L,all P < 0.05] in supernatant of HPMCs were significantly up-regulated in HG + LDL group,meanwhile the expression of PAI-1 mRNA was significantly higer than that in control group (P =0.022).Conclusions HPMCs uptake LDL into cells via LDL receptors.LDL can induce HPMCs transdifferentiation in the condition of high glucose,increase the secretion of Col Ⅰ,inhibit the degradation of ECM through up-regulating the expression of PAI-1,and lead to ECM accumulation.
2.Relevance of lipoprotein ( a ) and atherosclerotic renal artery stenosis: a Meta-analysis of observational studies
Peng XIA ; Lanping JIANG ; Limeng CHEN ; Xuemei LI
Chinese Journal of Clinical Nutrition 2012;20(1):1-5
Objective To explore the relevance between lipoprotein(a) and atherosclerotic renal artery stenosis in adults.Methods Literature search was conducted in PubMed and EMBASE Database,using “atherosclerotic renal artery stenosis” as the search term as well as in Wanfang Database,China National Knowledge Infrastructure,and Cqvip Database,using “renal artery stenosis” and “lipoprotein” as the search terms,aiming to find case-control or cohort studies published before 2010.The qualities of all the literatures enrolled were evaluated using Newcastle-Ottawa scale and the data from which were analyzed by the Review Manager 5.0 software.Results Five eligible case-control studies (661 cases) entered the Meta analysis.The results showed that the lipoprotein(a) level was not significantly higher in the case group than that in the control group [ mean difference =0.0702 g/L,95% CI ( - 0.0688,0.2092),P =0.32 ].Conclusion According to the existing studies,the relevance between lipoprotein(a) and atherosclerotic renal artery stenosis can not be established.
3.Survey of acute kidney injury in hospitalized patients
Ling QIU ; Limeng CHEN ; Xuemei LI ; Xinqi CHENG ; Xuewang LI
Chinese Journal of Laboratory Medicine 2009;32(1):46-50
Objective To investigate the incidence of AKI and its relationship to mortality of inpatients by analyzing the changes of serum creatinine(SCr). Methods We collected the data of SCr in Peking Union Medical College Hospital through Jun 2006 to May 2007 and then selected the patients who were subjected to SCr determination more than one time. The relationship between the frequency of SCr determination and gender, age was analyzed. The relationship of increased SCr to gender, age, frequency of determination was also analyzed. The risk stratification based on SCr was investigated. In our study, we investigated the incidence of AKI in different diagnostic groups. The relationship between AKI and mortality in ICU and MICU unit was analyzed. Results There were 36 855 patients in one year, 16 934 patients were subjected to SCr determination only one time, 15 233 patients were subjected to SCr determination at least two times. Elder men were subjected to SCr determination more frequently (P<0.01). Along with the increase of SCr concentration, the frequency of SCr determination were increased significantly (P<0.01). Using the increasing of SCr exceeding 50% as the criteria for diagnosis of AKI, the incidence of hospital-acquired AKI was 8.46%, and it was higher in patients with injury and poisoning (16.7%), infection (16.0%), hematological system diseases (16.1%), neoplasms (12.7%). The incidence of AKI was 27.7% and 55.2% in ICU and MICU, respectively. Mortality of patients in MICU was increased along with the increasing of SCr level Mortality of patients with AKI in ICU was 23.3%, that was significant higher than patients without AKI, the adjust OR was 2.7 (P<0.01). Conclusions The incidence of AKI evaluated by analyzing SCr changing is significantly higher than that using experienced clinical diagnosis. This method is convenient in clinic for early diagnosis of AKI.
4.Combining uric acid with lipoprotein a predicts the atherosclerotic renal artery stenosis in high risk patients
Peng XIA ; Ling QIU ; Yong ZENG ; Limeng CHEN ; Xuejun ZENG ; Xuemei LI ; Xuewang LI
Chinese Journal of Nephrology 2012;28(5):367-370
Objective To explore the value of uric acid (UA) combined with lipoprotein a [Lp(a)] in prediction of atherosclerotic renal artery stenosis (ARAS) in high risk population with atherosclerosis. Methods A total of 190 patients who were highly suspected for ARAS and received renal artery angiography in Peking Union Medical College Hospital from October 2008 to April 2011 were enrolled in the study.Among these patients,120 were diagnosed as coronary arterial disease (CAD) by coronary artery angiography and 89 were diagnosed as ARAS.The control group included 180 people undergoing routine healthy examination in our hospital.The basic information and lab results such as UA,Lp (a),total cholesterol (TC),triacylglycerol (TG),HDL,LDL,Scr and C-reactive protein (CRP) were collected.Logistic regression analysis was used to identify possible risk factors of ARAS and to establish a new tool to predict ARAS in the high risk population. Results The levels of Scr,UA,Lp (a) and CRP in ARAS cases were significantly elevated compared to control people.For high risk population,there were no significant differences in Scr,lipids,UA and CRP between ARAS cases and non-ARAS cases.Logistic regression analysis showed that UA level>344 μmol/L was correlated to ARAS independently.Using UA level>344 μmol/L and Lp (a) level>242 mg/L as a predicting marker for ARAS in high risk population,the specificity was 96.0%,the positive likelihood ratio was 5.45 (P=0.001),and the odds ratio was 6.78,95%CI (1.90~24.2) (P=0.001). Conclusions In high risk population,the UA may be an independent correlating factor of ARAS.Combining UA with Lp(a) can predict the ARAS.
5.Analysis of clinical and pathological features of 12 cases of Fabry disease
Jie MA ; Jianjun TIAN ; Yubing WEN ; Yan QIN ; Limeng CHEN ; Wenling YE ; Xuemei LI
Basic & Clinical Medicine 2015;(1):90-94
Objective To investigate the clinical and pathological features of Fabry disease in Chinese patients. Methods This retrospective study included all in-patients Fabry disease patients at PUMC Hospital from 2004 to 2014.Results The 12 patients included 10 males and 2 females.The middle age at onset was 10.The most fre-quent symptoms in our group were pain(10/12), angiokeratoma(9/12), renal abnormalities (7/12), hearing loss ( 6/12 ) , hypohidrosis ( 5/12 ) , cardiac abnormalities ( 5/12 ) , cerebrovascular abnormalities ( 3/12 ) and ophthalmological abnormalities ( 3/12 ) .The severe clinical manifestations were more frequently found in males . Electron microscopy plays a very important role in pathological diagnosis of Fabry disease .7 patients were suspec-ted to have family history .5 patients were examined regularly in which 4 cases were stable , and 1 patient re-ceived hemodialysis after 3 years'follow-up.Conclusions Onset of Fabry disease is early, many organs could be involved and patients may have different clinical manifestations.There are great differences in clinical features be-tween male and female patients .
6.Murine double minute 2: a novel mineralocorticoid-responsive gene involved in aldosterone-induced human mesangial cells line proliferation
Haiyun WANG ; Xuemei LI ; Limeng CHEN ; Lin DUAN ; Yan LI ; Xuewang LI
Chinese Journal of Nephrology 2011;27(5):363-368
Objective To investigate whether and how murine double minute 2(MDM2) was involved in aldosterone (ALD)-induced human mesangial cells line (HMCLs) proliferation. Methods RT-PCR and immunofluorescence were used to confirm the expression of MDM2 in HMCLs. Western blotting was used to estimate the relationship between ALD dose and MDM2 expression. Spironolactone, a mineralocorticoid receptor (MR) blocker, was used to estimate the role of MR on the up-regulation of MDM2 induced by ALD. Cycloheximide (CHX), a protein synthesis inhibitor, was used to estimate whether the rapid nongenomic mechanism was involved in the upregulation. To confirm the relationship among ALD, MDM2 expression and proliferation of HMCLs, small interference RNA of MDM2 was applied. Results Both MR and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) mRNAs were detected in HMCLs. MDM2 protein expression was also detected in both the nucleus and the cytoplasm. ALD significantly stimulated MDM2 expression, which implied that MDM2 was a novel mineralocorticoid-responsive gene in HMCLs. MR was involved in this process as spironolactone did not promote the expression of MDM2 mRNA or protein. ALD with CHX did not increase the expression of MDM2 protein, which indicated it was not directly regulated by the rapid nongenomic mechanisms. MDM2 protein was decreased by using the transfection of MDM2 siRNA and ALD did not promote the cell proliferation of HMCLs under the same conditions. All of which implied that MDM2 participated in ALQ-induced HMCLs proliferation. Conclusions MDM2 is a novel mineralocorticoid-responsive gene in HMCLs. MR is involved in ALD-induced MDM2 expression which is inhibited by spironolactone. The increased expression of MDM2 protein induced by ALD is not directly regulated by the rapid nongenomic mechanisms. MDM2 participates in ALD induced HMCLs proliferation.
7.Comparison of technical survival between Tenckhoff double-cuffed straight catheter and swan-neck curled tip catheter in peritoneal dialysis
Hong XU ; Bingyan LIU ; Dongyan LIU ; He XIAO ; Limeng CHEN ; Zijuan ZHOU ; Ying CUI ; Xuemei LI ; Yaug SUN ; Xuewaug LI
Chinese Journal of Nephrology 2009;25(6):441-444
objective To compare the technical survival between Tenckhoff double-cuffed straight catheter (TC)and swan-neck curled tip catheter (SNC) in peritoneal dialysis (PD). Methods Clinical data of 208 patients received PD in the Peritoneal Dialysis Center of Peking Union Medical College Hospital from January 1999 to December 2007 were analyzed retrospectively. All the patients were divided into two groups according to indwelling catheter. Technical survival and complications associated with the catheter between two groups were compared. Results Demographics and basic information were similar in both groups. The exit-site infection (ESI) rates of TC and SNC were 22.1% and 19.8% (P=0.786), and peritonitis rates of TC and SNC were 31.1% and 22.1% (P=0.159), which were slightly lower in SNC group, but the difference was not significant. Removal of the catheter was found in 27 (13.0%)patients, including 17 cases in TC group (13.9%) and 10 cases in SNC group (11.6%)(P=0.680).The median survival times of catheter in TC group and SNC group were 25 months and 22 months respectively without significant difference (P=0.103). Conclusions There are no significant differences of ESI rate, peritonitis rate and catheter survival between these two catheters in PD. The expensive swan-neck catheter offers no additional advantage. Doctors should choose the catheter according to the economic status of patients.
8.Validation of the new histopathological classification of ANCA associated glomerulonephritis and its correlation with renal outcome
Haiting WU ; Hang LI ; Wei YE ; Yubing WEN ; Jianfang CAI ; Mingxi LI ; Limeng CHEN ; Xuemei LI ; Xuewang LI
Chinese Journal of Nephrology 2017;33(5):349-355
Objective To assess the predictive value of Berden classification in ANCA associated glomerulonephritis.Methods Patients with confirmed ANCA associated glomerulonephritis were included,by retrieving the medical database in Peking Union Medical College Hospital from January 2000 to May 2015.Their detailed information during hospitalization and follow-up was recorded.The patients were divided into four categories based on Berden classification.The differences in clinical characters,renal function and response for treatment were compared.Results Among the 88 patients with ANCA-associated glomerulonephritis,19 (21.6%),21 (23.9%),32 (36.4%)and 16 (18.2%) patients were classified as focal,mixed,crescentic and sclerotic category.22 patients developed ESRD,and 19 patients died during follow up (1 patient developed ESRD before died).The mean estimated glomerular filtration rate (eGFR) at baseline was 68.04,25.45,30.04,15.16 ml·min-1·(1.73 m2)-1 (P < 0.05) in focal,crescentic,mixed and sclerotic category,respectively.During follow-up period,focal category always had the best renal function,while sclerotic category had the worst renal function.Crescentic category and mixed category were similar and in the middle.Remission rate at 6m was 62.5%,73.7%,57.5%,30.8%(P > 0.05).And crescentic category had the greatest improvement in eGFR at 6m.Conclusions Focal category had relatively preserved renal function and favorable renal outcome,while the sclerotic category had the worst renal outcome.Crescentic and mixed category had an intermediate outcome.We support the use of the Berden classification in predicting the renal prognosis of patients with ANCA associated glomerulonephritis.
9.Clinical and pathological analysis of patients presenting renal lesion and monoclonal gammopathy
Chao LI ; Yubing WEN ; Hang LI ; Wei SU ; Jian LI ; Jianfang CAI ; Mingxi LI ; Limeng CHEN ; Xuemei LI ; Xuewang LI
Chinese Journal of Nephrology 2017;33(6):422-428
Objectives To analyze the spectrum of renal diseases associated with monoclonal gammopathy and unrelated renal diseases.Methods Hospitalized patients in Peking Union Medical College Hospital who underwent renal biopsy between January,2013 and December,2015.They had monoclonal gammopathy on serum protein electrophoresis (SPE),serum immunofixation electrophoresis (IFE),urine IFE and/or serum free light chain (FLC).64 patients met the inclusion criteria and were classified as monoclonal gammopathy of renal significance (MGRS) (n=36),monoclonal gammopathy of undetermined significance (MGUS) (n=17) and hematologic malignancy (n=11).Results Renal lesions in MGRS subgroup included light chain amyloidosis (n=28,77.8%),light chain deposition disease (n=7,19.4%),and fibrillary glomerulopathy (n=l,2.8%).eGFR in light chain amyloidosis subgroup differed significantly,compared with light chain deposition disease [eGFR 93 ml· min-1 · (1.73m2)-1 vs 28 ml· min-1 · (1.73 m2) 1,P < 0.01],as well as HTN incidence (35.7% vs 100.0%,P < 0.01).Renal diseases in MGUS subgroup included membranous nephropathy (n=10,58.8%),focal segmental glomerulosclerosis (n=3,17.6%),diabetic glomerulopathy (n=l,5.9%),Henoch-Schonlein purpura nephritis (n=l,5.9%),anti-glomerular basement membrane disease concurrent with membranous nephropathy (n=l,5.9%) and glomerulomegaly (n=l,5.9%).Various renal lesions related/unrelated to hematologic malignancy were seen in third subgroup,including light chain cast nephropathy (n=3,27.3%),tubulo-interstitial lesions (n=2,18.2%),light chain amyloidosis (n=1,9.1%),light chain deposition disease(n=1,9.1%),IgA nephropathy (n=1,9.1%),mesangial proliferative glomerulonephritis (n=l,9.1%),endocapillary proliferative glomerulonephritis (n=1,9.1%) and acute tubular necrosis (n=1,9.1%).Positive rates of SPE,serun IFE and urine IFE in MGRS subgroup were 40.6%,52.8% and 69.4%,respectively.Positive rates of SPE,serum IFE and urine IFE in MGUS subgroup were 68.8%,100.0% and 37.5%,respectively.Positive rates of SPE,serum IFE and urine IFE in hematologic malignancy subgroup were 54.5%,72.7% and 81.8% respectively.MGRS and MGUS subgroups differed significantly in positive rate of serum IFE (P < 0.001).Abnormal rates of serum FLC ratio in above three subgroups were 83.3%,17.6% and 90.9%,respectively,with that in MGUS group being significantly lower than the rates in other two groups (P < 0.001,respectively).Conclusions The significance of monoclonal gammopathy in patients with renal disease should be evaluated by other clinical data,as well as renal pathology.
10.Characteristics and risk factors of lethal peritoneal dialysis related peritonitis
Ying WANG ; Xiaowei DENG ; Yang LI ; Haiyun WANG ; Zijuan ZHOU ; Wei YANG ; Ying CUI ; Jing LIANG ; Xuemei LI ; Limeng CHEN
Basic & Clinical Medicine 2017;37(8):1152-1156
Objective To analyze the characteristics of lethal peritoneal dialysis related peritonitis and to define the risk factors.Methods All patients who developed PD related peritonitis between Jan.1999 and May 2015 in PUMCH were included.Clinical profiles were collected.Patients were divided into mortality group(n=16) and non-mortality group(n=182) according to whether peritonitis causing mortality.Baseline clinical profiles were compared between two groups.Cox regression analysis was used to define the risk factors for mortality.Results White blood cells [(10.2±6.3)×109/L vs (5.8±1.8)×109/L,P<0.05] increased,but serum albumin[(25.2±8.5)g/L vs (34.0±6.3)g/L,P<0.05] and potassium concentration [(3.5±0.9)mmol/L vs (4.5±1.0)mmol/L,P<0.05] decreased at the time of lethal peritonitis bacteria and fungus cultures were positive in half of the patients as bacteria (31.2%),fungus (12.5%)and mycobacterium tuberculosis (6.25%).Multiple cox regression analysis identified cardiovascular disease as the independent risk factor for peritonitis related mortality (HR 9.318,95% CI 1.875~46.305,P<0.01).Conclusions Peritonitis of patients with cardiovascular disease may cause death.