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Objective To investigate the clinical and pathological features of patients with a combination of Sjogren's syndrome (SS) and antineutrophil cytoplasmic antibody (ANCA) associated vasculitis with renal involvement.Methods By searching the Peking Union Medical College Hospital medical database and literature between January 1990 and June 2017,patients had a combination of SS and ANCA associated vasculitis with renal involvement were included.Data of clinical information,autoimmune antibodies,renal manifestations and renal pathology were retrieved and analyzed.Results Eighteen patients were enrolled:4 from our hospital and 14 from literature.SS was diagnosed no later than ANCA associated vasculitis in all the patients,among which 83.3％(15/18) of patients had extra-glandular and extra-renal organs involved.All the patients were tested positive for myeloperoxidase (MPO)-ANCA,and only two were protein 3 (PR3)-ANCA positive concurrently.The positivity rates of antinuclear antibody (ANA),rheumatoid factor (RF),anti-SSA antibody,and anti-SSB antibody were 83.3％(15/18),55.6％(10/18),77.8％(14/18),and 38.9％(7/18),respectively.The renal manifestations were characterized by renal insufficiency with a median serum creatinine of 174 μmol/L,hematuria,moderate proteinuria with a median 24 hour urine protein of 1.70 g,and necrotizing vasculitis with oligo-immune complex and varying degrees of interstitial damage in pathology.Conclusions A combination of Sjogren's syndrome and ANCA associated vasculitis with renal involvement is rare in clinical setting,and almost all of the patients are MPO-ANCA positive,with high probability of ANA positivity and extra-glandular involvement.Physicians should beware of ANCA associated glomerulonephritis in SS patients with inexplicable renal dysfunction and renal biopsy should be carried out in time.
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Objective To investigate the clinicopathological characteristics of IgAN patients with massive proteinuria,as well as their treatment response to glucocorticoids and long-term prognosis.Methods Clinical and pathological parameters were collected in patients diagnosed with IgA nephropathy in our hospital from Jan 2003 to Oct 2015.Patients were followed up for at least six months under the treatment with full dosage of glucocorticoids.Responses of patients with and without nephrotic syndrome were compared.Results A total of 156 patients were enrolled for the analysis (86 patients in the nephropathic proteinuria group,and 70 patients in the nephrotic syndrome group).Patients presented with nephrotic syndrome showed higher proportion of IgM deposition in renal slides.There exited no difference in treatment response to glucocorticoids between the two groups.Patients with full or partial remission showed a better prognosis by Kaplan-Meier analysis than no remission group (P ＜ 0.001).The ratio of segmental sclerosis was negatively correlated with treatment response to glucocorticoids by multiple linear regression (3 value=-0.330,P ＜ 0.001).Multivariate Cox regression model showed that glomerular density (HR=0.45,P=0.02) and eGFR (HR=0.95,P=0.001)were independent influential factors for renal survival.Conclusions Patients presented with nephrotic syndrome show higher proportion of IgM deposition in renal slides.Patients in remission after treatment with 6-month glucocorticoids present a better prognosis than no remission patients,and glomerular density as well as eGFR are independent influential factors for renal survival.
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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.
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Objective To observe the circadian blood pressure (BP) rhythms and the phase of heart circadian gene expression in adriamycin (ADR)-induced nephropathy rats,thus exploring the effect of circadian systems on circadian BP variation in nephrotic rats.Methods Sprague-Dawley (SD) male rats (8 weeks) were housed in a 12∶12 hour light/dark cycle in two weeks,and randomly divided into ADR group and control group.ADR rats were injected 6.5 mg/kg adriamycin via vein to establish nephrotic rats model two weeks later,while control rats were injected the equal volume of saline.Five rats in each group were implanted with the radio-telemetry into abdominal aortic.After seven days,systolic blood pressure (SBP),diastolic blood pressure (DBP),mean arterial pressure (MAP) and heart rate (HR) were recorded every one minute during 72 hours via radio-telemetry.Three rats in each group were sacrificed in six time points (zeitgeber time=02:00,06:00,10:00,14:00,18:00,22:00) to get the blood sample and heart tissue,respectively.The mRNA expressions of core clock gene CLOCK,BMAL1,Per1,Per2,Cry1 and Cry2 in heart issue were evaluated by the real-time quantitative PCR.The plasma levels of renin activity angiotensin Ⅱ and aldosterone were measured by radioimmunoassay.All the data were analyzed by a partial Fourier analysis and stepwise regression.Results (1) There was no significant difference in 24 h average of SBP,DBP and MAP between two groups.In control group,there was higher SBP (3.22 mmHg),DBP (1.16 mmHg) and MAP (3.19 mmHg) in dark period than those in light period,only SBP and MAP showing statistical difference (all P ＜ 0.05).However,SBP,DBP and MAP had no significant difference between dark and light in ADR group (all P ＞ 0.05).(2) Control rats had (8.0+24.0) h rhythm of SBP,and their DBP,MAP and HR appeared 24.0-hour normal circadian pattern (all P ＜ 0.05).In ADR group,the rhythm of SBP completely disappeared.And their DBP and MAP remained 24.0 h circadian rhythm,but the peak time advanced 1.5 h to 3.0 h compared with SD rats.(3) In SD controls,daily rhythms period of the core clock genes (CLOCK,BMAL1,Cry1,Cry2,Per1 and Per2) mRNA expression in the heart were (4.8+ 12.0) h,24.0 h,12.0 h,(12.0+24.0) h,(4.8+12.0) h and 12.0 h (all P ＜ 0.05),respectively.In ADR rats,the rhythm of CLOCK,BMAL1,Cry2,Per1 and Per2 mRNA completely disappeared (all P ＞ 0.05).The circadian rhythm of Cry1 mRNA remained,but the period was changed from 12.0 h to (4.8+6.0) h.(4) The plasma renin and aldosterone concentration presented 12.0 h and 24.0 h daily rhythms in SD rats (all P ＜ 0.05).These diurnal changes however completely disappeared in ADR rats (all P ＞ 0.05).Conclusions ADR nephrotic rats lose the circadian rhythm of BP with the disturbances of cardiac circadian clock system.The disrupted diurnal rhythm of the core clock genes (CLOCK,BMAL1,Cry2,Per1 and Per2) mRNA expression in the heart may regulate the pathological circadian rhythms of heart tissue,which is involved with disturbances of circadian rhythm of BP.
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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.
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Objective To evaluate the predictive factors and renal outcomes of idiopathic membranous nephropathy (IMN) in patients with type 2 diabetes (T2DM).Methods In this retrospective study,clinical data of 101 IMN patients with T2DM and 96 patients with diabetic nephropathy (DN) were consecutively collected.Logistic regression was used to assess potential clinical factors indicating IMN and COX regression was employed to analyze risks of IMN in developing to endstage renal disease (ESRD),as compared with that of DN,in patients with T2DM.Results In a multivariate model,age ≥55 years old,presence of nephrotic syndrome,estimated glomerular filtration rate (eGFR) ＞ 60 ml · min-1 · (1.73 m2)-1,duration of diabetes≤5 years and absence of diabetic retinopathy,were associated with IMN,as compared with DN,in patients with T2DM.In T2DM patients presented with nephrotic syndrome,age≥55 years old,eGFR ＞ 60 ml· min1· (1.73 m2)-1,duration of diabetes≤5 years and absence of diabetic retinopathy,were also associated with IMN,as compared with DN.Receiver operating characteristic curve (ROC) showed eGFR 65.5 ml · min-1 · (1.73 m2) 1 was an optimal cutoff in differentiating DN and IMN.DN was associated with 16.8 times as high risk of incident ESRD as compared with IMN in T2DM patients.Conclusions In patients with T2DM,age≥55 years,presence of nephrotic syndrome,early stage of CKD,duration of diabetes≤5 years and absence of retinopathy,may indicate IMN rather than DN.T2DM patients with IMN have much better renal prognosis as compared with DN.
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Objective To discuss the relationship between serum anti-Phosphalipase A2 receptor (PLA2R) antibodies and glomerular IgG4 subclass in patients with membranous nephropathy and evaluate the diagnostic value of the two markers.Methods Patients diagnosed as membranous nephropathy from October 2011 to April 2014 in Peking Union Medical College Hospital were included and divided into IMN and SMN groups accoding to their clinical diagnosis.Serum anti-PLA2R antibodies and glomerular IgG subclasses were both detected by indirect immunofluorescence assay.Receiver operator characteristic curves were used to evaluate the diagnostic efficiency of anti-PLA2R antibodies and glomerular IgG4.Results Prevalence of serum anti-PLA2R antibodies of IMN patients was 69.5％ (41/59); prevalence of MLN patients was 4.8％ (1/21).Within the IMN group,thirty-five patients showed positive results of both serum anti-PLA2R antibodies and glomerular IgG4; Six patients were positive for serum anti-PLA2R antibodies but negative for glomerular IgG4; Seventeen patients were positive for glomerular IgG4 but negative for serum anti-PLA2R antibodies; one patient was negative for both tests.The sensitivity of serum anti-PLA2R antibody was 69.5％ and the specificity was 95.2％; the sensitivity of glomerular IgG4 was 89.8％ and the specificity was 52.3％.The sensitivity of the combined marker consisting of serum anti-PLA2R antibody and glomerular IgG4 was 59.3％ and the specificity was 100％.Four out of the six patients secondary to HBV infection,one out of the three patients secondary to Sj(o)gren syndrome,one out of the three patients secondary to malignant tumor showed positive results of serum anti-PLA2R antibodies.Conclusions Serum antiPLA2R antibodies were of high prevalence among IMN patients; the prevalence among SMN patients varied with etiologies.Results of serum anti-PLA2R antibodies and glomerular IgG4 were helpful to rule out secondary etiologies in the diagnosis of membrnous nephropathy.
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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.
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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.
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ObjectiveTo establish the urinary proteome profile of the metabolic syndrome ( MetS ) patients,compare the different urinary proteins between the MetS patients and the normal individuals,and analyze the function of the different proteins,so as to explore the pathogenesis of MetS.MethodsOvernight urine were collected from normal controls (n =6) and MetS patients ( n =6).Acetone precipitation method was used to precipitate proteins of urine.Intra-group proteins were mixed together,identified by reversed phase liquid chromatography-mass spectrometry/mass spectrometry and quantified relatively using spectral counting method.The functions of differential proteins were analyzed using Panther.ResultsA total of 807 and 630 proteins were identified respectively in normal controls and MetS patients.Comparing MetS patients with normal controls,sixty different proteins were found,of which 23 proteins were up-regulated and 37 proteins were down-regulated in MetS patients.In the up-regulated proteins,plasminogen was involved in the plasminogen activation cascade and isoform of alphaenolase,phosphoglycerate kinase 1 and fructose-bisphosphate aldolase B down-regulated in MetS patients were involved in the process of glycolysis and fructose metabolism.ConclusionsThe urinary proteome profile of patients with MetS was established by reversed phase liquid chromatography-mass spectrometry/mass spectrometry.Different proteins between MetS patients and normal people were identified.The plasminogen activation cascade,glycolysis and fructose metabolism play key roles in the pathogenesis of MetS.
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Phospholipase A2 receptor,a transmembrane protein located on glomerular podocytes,had been proved to be the target antigen in idiopathic membranous nephropathy and provided us a new road to uncover the mechanisms of its pathogenesis.In this review,we described the structure and physiological function of phospholipase A2 receptor and highlighted the role of its autoantibody in idiopathic membranous nephropathy.Finally we suggested several possible aspects of its future clinical application.( Chin J Lab Med,2012,35:792-794 )
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ObjectiveTo investigate the impacts of different serum creatinine detection methods,including Jaffe and enzymatic methods,on the efficacy of different GFR estimation equations in CKD patients in China.MethodsrGFR of 176 patients with CKD were determined by dual plasma sample method 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA) plasma clearance rate.Serum creatinine was detected with four kinds of creatinine reagents from different manufacturers.Cockcroft-Gault Equation corrected for body surface area (CG/BSA),simplified Modification of Diet in Renal Disease (MDRD) Study equation,IDMS-traceable MDRD equation,CKD epidemiology collaborative research (CKD-EPI) equation and two Chinese simplified MDRD equation (project group equation 1,2) were applied to calculate estimated GFR (eGFR)respectively.eGFRwerecomparedwithrGFRforthecorrelation, deviation, precisionand30％ accuracy.ResultsThe mean rGFR of 176 patients with CKD,was [ 40.70 ( 19.41 -84.35 ) ] ml · min- 1 ·( 1.73 m2 ) -1.For all GFR estimation equations,there were significant differences in eGFR results between enzymatic method and Jaffe method,when analyzed by the Wilcoxon signed-rank test.eGFR results assessed by two enzymatic creatinine detection systems showed no significant difference,while eGFR results analyzed by two Jaffe detection system were significantly different.The intraclass correlation coefficient (ICC) of eGFR and rGFR ranged from 0.879 to 0.923 by Jaffe method,while from 0.925 to 0.946 by enzymatic creatinine method.ICC and Pearson correlation analysis revealed a significant correlation between eGFR and rGFR,and the correlation was better when using enzymatic method.Bland-Altman plots indicated that large deviation occurred in the high value area of GFR using various equations.However,deviation with the enzymatic creatinine method was smaller than that with the Jaffe method. When rGFR ≥ 60 ml · min- 1 ·(1.73 m2) -1,the 30％ accuracy of eGFR using enzymatic creatinine method for all six equations was between 68.3％ and 90.0％,while it was between 41％ and 75％ when using Jaffe method. The 30％ accuracy of eGFR using enzymatic creatinine method was significantly higher than that using picric acid method for these equations except for the project group equation 1.When rGFR ＜60 ml · min -1 · ( 1.73 m2 ) -1,the 30％accuracy of eGFR using both methods was between 39.7％ -49.1％,40.5％ -52.6％respectively,and the difference of data showed no statistical significance.For the same equation,there was a significant differernce in 30％ accuracy of eGFR between two enzymatic creatinine detection systems,while there was no significant differernce between two Jaffe creatinine detection systems.ConclusionsA significant difference was demonstrated in the same GFR evaluation equation using two different creatinine detection methods (Jaffe method and enzymatic method).The correlation between rGFR and eGFR,the degree of deviation,and accuracy of eGFR results assessed by enzymatic creatinine method were better than those by Jaffe method.The eGFR results assessed by different enzymatic detection systems revealed no significant difference.
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ObjectiveTo explore the relationship of body fat distribution with serum lipid and its potentially predictive value for dyslipidemia.MethodsA total of 784 Beijing rural residents were enrolled in this study using a cluster sampling method.The body height,weight,waist circumference (WC),hip circumference,body composition,high-density lipoprotein cholesterol ( HDL-C ),low-density lipoprotein cholesterol ( LDL-C),total cholesterol ( TC),and triglycerides (TG) were measured.The body mass index (BMI) and waist to hip ratio (WHR) were calculated.ResultsThe age-adjusted partial correlation analysis showed that WC had the best correlation with HDL-C ( r =- 0.310) and LDL-C ( r =0.204 ),while WHR with TC ( r =0.151 ) and TG ( r =0.271 ).Subgroup analysis with different BMI,WC,WHR,and trunk fat mass (TFM) showed that WC,WHR,and TFM sensitively reflected the changes of body lipids,whereas BMI,WC,WHR,and TFM sensitively reflected the low HDL,high TG,and risk of dyslipidemia.Receiver operating characteristic curve analysis showed that the predictive curves of WC,WHR,BMI,and TFM were above the reference line,and the areas under the receiver operating characteristic curves of WHR (0.684,0.630),WC (0.667,0.616),and TFM (0.661,0.604) showed high tendencies than BMI (0.629,0.597) for both male and female subjects,although no statistically significant differences were found ( all P ＞ 0.05 ).ConclusionsCompared with BMI,the body fat distribution indicators including WHR,WC,and TFM have higher predictive values in evaluating the risk of dyslipidemia.When the maximum Youden index for predicting the risk of dyslipidemia is applied,the ideal cutoff points was 24 kg/m2 for BMI,0.91 for WHR,85cm for WC,7.5kg for TFM in males,and 25 kg/m2,0.91,87cm,and 9.5 kg,respectively,in females.
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Objective To investigate the relationship between the urinary albumin excretion (UAE) and serum uric acid in general population. Methods The study participants were derived from the epidemiological study on the association of metabolic syndrome and chronic kidney disease (CKD) in Pinggu district, Beijing. A total of 992 participants (463 men and 529 women) aged from 30 to 75 years were enrolled in this study. For each participant, UAE, serum uric acid, serum creatinine, and serum lipids were detected and other potential risk factors for CKD were surveyed. Results ( 1 ) The frequencies of microalbuminuria, macroalbuminuria and hyperuricemia were 12.9% , 1.8% and 4.3% respectively. The persons with hyperuricemia had significantly higher frequency of albuminuria than those without hyperuricemia (37. 2% vs 13. 7% , P ＜0. 01). (2) The participants were divided according to the quartiles (25% , 50% , 75% ) of serum uric acid level, and the frequencies of albuminuria in males were 13. 2% , 13. 9% , 17. 2% and 25.4% , while those in females were 8. 4% , 6. 2% , 9. 6% and 24. 8%. ( 3 ) Multivariate logistic regression analysis showed, hyperuricemia was significantly associated with albuminuria in females (OR =2. 31, 95% CI 1. 15-4. 68; P=0.02), but not in males. If the persons with reduced renal function were excluded, similar result still could be gained. Conclusions The prevalence of albuminuria increases gradually with uric acid elevation. Serum uric acid is an independent risk factor of elevated UAE, especially in females.
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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.
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objective To analyze the clinicopathological features and prognosis of antiglomerular basement membrane(GBM)disease,and evaluate the efficacy and safety of double filtration plasmapheresis(DFPP). Methods A total of 35 hospitalized patients diagnosed as anti-GBM disease in our department were enrolled in the study.All the patients were divided into 3 groups according to the manifestations at admission.Group Ⅰ∶24 patients with severe pulmonary hemorrhage or rapidly progressive glomerulonephritis(RPGN)received pulse methylprednisolone with or without DFPP,and then followed by prednisone and CTX.Group Ⅱ∶5 patients without severe pulmonary hemorrhage and RPGN received prednisone and CTX.Group Ⅲ∶5 ESRD patients and 1 normal renal function patient did not receive immunosuppression therapy.Anti-GBM antibody titer of pre-and post-DFPP in 4 patients was measured consecutively,and removal rate was calculated.Results The mean age of all the patients was(41.1±16.6)years.Sixteen patients(45.7%)presented Goodpasture's syndrome.Eighteen patients(51.4%)had anti-GBM glomerulonephritis alone,whereas one suffered solely from pulmonary hemorrhage.20%patients had positive P-ANCA serology.54.2%crescentic glomerulonephritis and 7 with other glomerulonephritis were revealed by kidney biopsy in 24 patients.Patients in Group Ⅰ showed more severe manifestation at admission:higher Scr level,higher titer of anit-GBM antibody,greater percentage of crescents.Within the follow-up period,7 patients died and kidneys of 50%patients survived.No patient died in Group Ⅱ and Ⅲ.The elder age,anemia,higher Scr(＞300 μmol/L),oliguria or anuria,emergency hemodialysis at admission,and more glomerular sclerosis were predictors of poor prognosis.The anti-GBM antibody was negative after 4 to 6 sessions of DFPP.and the mean removal rate was 55%.During total 94 DFPP sessions,there was no unacceptable morbidity. Conclusions Different therapy strategy is necessary for anti-GBM disease with different clinical manifestations.DFPP is an effective and safe clearance way of anti-GBM antibody.
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Objective To investigate the clinicopathologic characteristics, classification and outcome in lupus nephritis(LN)patients with thrombotic microangiopathy(TMA). Methods LN patients with TMA proven by renal biopsy, from January 2000 to February 2009 in our hospital were enrolled. They were classified as poly-immunocomplex deposit group(n =35)and pauci-immunocomplex deposit group(n=25). Their clinicopathologic features and outcome were analyzed retrospectively. Results(l)The incidence of TMA in lupus nephritis was 9.2%(n=62), which presented severe hypertension, prominently elevated serum creatinine, anemia, thrombocytopenia, and was also the poorest prognosis of all the vascular lesion types. The incidence of death/end stage renal disease(ESRD)was 25.0%, with a mortality rate of 13.6%.(2)According to immunocomplex deposit in renal tissue, LN complicated with TMA could be classified as "poly immunocomplex deposit subtype" and "pauci-immunocomplex deposit subtype". The former presented better response to steroid and immunosuppressant therapy, in spite of more active clinicopathologic manifestations. The incidences of death/ESRD of poly subtype and pauci subtype were 8.8% and 32.0% respectively. Conclusions TMA presenting severe manifestations and the poorest prognosis is not rare in LN. LN with TMA may be classified as poly-immunocomplex deposit subtype and pauci-immunocomplex deposit subtype. This classification may be helpful in prognosis because the latter shows bad response to steroid-immunosuppressant therapy.
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Objective To investigate the efficacy differences of different doses of cyclophosphamide(CTX)among subcategories of diffuse proliferative lupus nephritis(LN). Methods Clinical data of 133 LN patients diagnosed by renal biopsy with class IV or class IV +V who were treated with corticosteroid plus CTX were analyzed retrospectively. The baseline Scr, 24 h urine protein, CTX dosages and prognosis were compared among different dosages for each subcategory. Results The average cumulative dose of CTX within 6 months was(11.1 4.1)g. The high dose group was >12 g, the medium dose group was >6-12 g and the low dose group was ≤6 g. Compared to low dose group, high dose CTX increased the remission rate of class Ⅳ +Ⅴ(67% vs 40%, P=0.314)and chronic renal lesion(43% vs 0%, P=0.212), but such enhancement was not obvious in class Ⅳ(Ⅳ-S: 67% vs 50%, P=0.548, Ⅳ-G: 65% vs 70%, P= 0.560). Difference of overall adverse reactions was not significant between high dose group and low dose group(51% vs 37% ,P=0.224). Conclusion Corticosteroid plus high dose CTX may improve the remission rate of patients with class IV + V and chronic renal lesions.
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Objective To analysis if intedeukin-1β (IL-1β) can regulate human mesangial cells (HMC) to uptake oxidized low density lipoprotein (Ox-LDL) and if the effect of IL-lβ be changed through the lectin-like oxidized low-density lipoprotein receptor 1 (LOX-l)pathway. Methods The uptake of HMC to Ox-LDL stimulated by IL-1β was observed using Oil Red "O" and flow cytometry. The level of LOX-1 in HMC induced by IL-1β and Ox-LDL was examined using real-time PCR and Western blotting. Results Uptake of Ox-LDL and Dil-Ox-LDL by HMC was up-regulated upon stimulation with IL-1β in a dose- and time-dependent manner. Intracellular mean fluorescence density of Dil-Ox-LDL with LOX-1 blocker in IL-1β stimulation group was decreased compared to that without blocker. The peak level of LOX-1 mRNA reached after 6 h of stimulation and was as high as 6.87-fold of control. IL-1β could induce LOX-1 mRNA expression in a dose-dependent manner. Treated with 10 μg/L IL-1β for 12 h, the upregulation effect on LOX-1 mRNA was as high as 6.57-fold of control. IL-1β could induce LOX-1 protein expression in a time- and dose-dependent manner. The peak level of LOX-1 protein reached after 24 h of stimulation of 5 μg/L IL-1β and was as high as 1.88-fold of control. Treated with 10 μg/L IL-1β for 24 h, the up-regulation effect on LOX-1 protein reached peak and was as high as 2.57-fold of control. IL-1β could induce LOX-1 mRNA and protein expression in a dosedependent manner. Conclusion The expression of LOX-1 can be up-regulated by IL-1β in a dose-dependent manner and the enhanced uptake of HMC to Ox-LDL stimulated by IL-1β partly through the LOX-1 pathway, which means the dyslipidemia of HMC can be enhanced by inflammatory cytokines.
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Objective To study the pathologic pattern and clinical feature of type 2 diabetes mellitus complicated with chronic kidney diseases (CKD). Methods Clinicopathological features of 155 type 2 diabetic patients complicated with CKD were collected and analyzed retrospectively. The patients were divided into four groups: typical diabetic glomerulopathy (DG),atypical diabetes-related renal disease (ADRD), non-diabetic renal diseases (NDRD) and DG complicated with NDRD. Results Renal biopsies revealed DG accounted for 18.7% of the patients, ADRD accounted for 12.9%, NDRD accounted for 60.0%, and DG complicated with NDRD accounted for 8.4%. In DG group, duration of type 2 diabetes was longer;the level of fast blood glucose, systolic blood pressure, mean arterial pressure and prevalence of diabetic retinopathy (DR) were higher;proteinuria was heavier and evaluated glomerular filtration rate (eGFR) was lower. In ADRD group, body mass index and prevalence of obesity were higher;dyslipidemia was more severe. Gross hematuria and acute renal insufficiency could be only found in NDRD group.Without DR, duration of diabetes under 5 years, gross hematuria, acute renal insufficiency,evidences of autoimmune diseases and proteinuria≥3.5 g/24 h but eGFR ≥60 ml/min were specific valuable predictors for NDRD. Conclusions Renal injuries in type 2 diabetic patients are structural heterogeneous, in which NDRD is more common and is different from ADRD and DG.Renal biopsy should be considered when type 2 diabetic patients complicated with CKD present at least one characteristic as follows: duration of diabetes under 5 years, without DR, history of gross hematuria, acute decrease of renal function, evidences of autoimmune diseases and proteinuria ≥ 3.5 g/24 h but eGFR ≥ 60 ml/min.