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1.
Chinese Journal of Nephrology ; (12): 401-406, 2019.
Article in Chinese | WPRIM | ID: wpr-756070

ABSTRACT

Objective To evaluate the diagnostic value of pathological features of atypical membranous nephropathy (AMN). Methods Ninety - one patients with AMN diagnosed by renal biopsy during 2011 and 2017 were enrolled in this study. On the basis of M - type phospholipase A2 receptor (PLA2R) and thrombospondin type - 1 domain - containing 7A protein (THSD7A) by immunohistochemistry, patients were divided into AMN group (25 cases without PLA2R and THSD7A) and idiopathic membranous nephropathy (IMN) group (66 cases with positive PLA2R or THSD7A). The results of immunofluorescence (IF), light microscopy (LM) and electron microscopy (EM) of these two groups were compared, and the parameters with statistical difference were screened out in order to assess their value in the diagnosis of AMN in fourfold table. Results IF results showed that in AMN group the proportions of IgG deposition on capillary wall and mesangial area as well as positive otherIgG subclasses and complement C1q but negative IgG4 were significantly higher than those in IMN group (respectively, 56.0% vs 12.1% , 44.0% vs 0, both P<0.05). Their diagnostic specificities for AMN were 87.9% and 100.0%, respectively. However, the positive rates of IgG accompanied with IgA and/or IgM, predominant IgG4 with other IgG subclasses and complement C1q in two groups were not significantly different (all P>0.05). LM results showed that the proportions of false double track sign on basement membrane and fuchsinophilic proteins under epithelium, endothelium, basement membrane and mesangial region in AMN group were significantly higher than those in IMN group (respectively, 36.0% vs 0, 44.0% vs 1.5%, both P<0.05). Their diagnostic specificities for AMN were 100.0% and 98.5% , respectively. However, the scores of mesangial cell proliferation of these two groups showed no significantly difference (P>0.05). EM results showed that the rate of endothelial electron dense deposits in AMN group was significantly higher than that in IMN group (36.0% vs 1.5%, P<0.05), and its diagnostic specificity for AMN was 98.5%. Conclusions IgG deposition on both capillary wall and mesangial area, positive other IgG subclasses and C1q with negative IgG4, false -double contour sign, multi - site fuchsinophilic deposits and endothelial electron dense deposits may help for the AMN diagnosis in the absence of PLA2R and THSD7A related data.

2.
Chinese Journal of Nephrology ; (12): 274-280, 2018.
Article in Chinese | WPRIM | ID: wpr-711109

ABSTRACT

Objective To evaluate the efficacy and safety of tolvaptan therapy for edema in patients with nephrotic syndrome(NS).Methods Twelve patients with NS who had normal serum sodium and blood volume were enrolled.All of them were treated with oral tolvaptan of 15-30 mg per day for 7 days.The diuretic effects were observed and the adverse reactions including electrolyte disorders(especially hypernatremia),low blood volume,thromboembolic complications,and acute kidney injury were closely monitored.Results The average urine volume was significantly increased(F=5.792,P < 0.001)and the body weight was significantly decreased(F=24.086,P < 0.001)from the first day of tolvaptan therapy until the end of the treatment.The average serum sodium levels were significantly increased from the second day of tolvaptan therapy until the end of the treatment(F=2.790,P=0.012),but only 3 case-times(3.6%)among the total 84 case-times of serum sodium tests showed mild hypernatremia(the highest level 146.5 mmol/L)and all the hypernatremia returned back to normal after suspending tolvaptan for one day.There were no significant changes in the serum potassium levels(F=0.477,P=0.849)within the whole treatment course.There was also no significant difference of the blood volume between the level at the end of treatment and the baseline level[(74.3± 3.0)ml/kg vs(74.9±3.0)ml/kg,P=0.855].The thromboembolic complications and acute kidney injury both also did not take place.Conclusions As long as a rational and prudent treatment regimen is applied,tolvaptan has good diuretic effects and safety for treatment of edema in the NS patients with normal serum sodium and blood volume.

3.
Chinese Journal of Nephrology ; (12): 881-886, 2018.
Article in Chinese | WPRIM | ID: wpr-734911

ABSTRACT

Objective To investigate whether the clinical and pathological injury of kidney in IgA nephropathy (IgAN) patients with hypertension is associated with circadian blood pressure rhythm change, particularly with elevated nocturnal blood pressure (BP). Methods This study was a retrospective cross-sectional study. Clinic and renal histopathological injury data were obtained from 83 IgAN patients with hypertension. First, 24 h ambulatory BP monitoring (ABPM) data were analyzed. Second, all these IgAN patients were divided into two groups, elevated nocturnal BP group and nocturnal normotensive BP group, and the clinical and pathological differences between this two groups were analyzed. Third, logistic regression analysis was used to analyze the influencing factors of renal tubulointerstitial injury in IgAN patients with hypertension. At last, all these IgAN patients were divided into two groups according to the level of estimated glomerular filtration rate (eGFR), group of patients with eGFR≥60 ml·min-1·(1.73 m2)-1 and the other group with eGFR<60 ml·min-1·(1.73 m2)-1, and the 24 h ABPM data were compared. Results (1) The proportion of non-dipper circadian rhythm of BP in IgAN patients with hypertension was 79.5%. (2) Compared with nocturnal normotensive BP group, patients in elevated nocturnal BP group had significantly higher levels of 24-hour urinary protein quantity and blood uric acid (both P<0.05), and lower eGFR and urine osmotic pressure clinically (both P<0.05). Index of interstitial fibrosis and tubular atrophy was significantly higher in nocturnal normotensive BP group (P<0.05), while the proportion of glomerular ischemia lesion was not significantly different between two groups. (3) Multivariate logistic regression analysis showed that elevated nocturnal BP was an independent risk factor for severe tubulointerstitial injury of IgAN (OR=1.113, 95%CI 1.038-1.192, P=0.002). (4) Compared with the group of eGFR≥60 ml·min-1·(1.73 m2)-1, 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP), daytime SBP and DBP, nocturnal SBP and DBP were significantly higher in group of eGFR<60 ml·min-1·(1.73 m2)-1 (all P<0.05). Conclusion The proportion of non-dipper circadian rhythm of BP in IgAN patients with hypertension is as high as 79.5%. Elevated nocturnal BP is associated with the severity of renal damage, and elevated nocturnal BP is an independent risk factor for severe tubulointerstitial injury in IgAN patients with hypertension. Therefore, 24 h ABPM should be emphasized, and elevated nocturnal BP should be well controlled to slow the progression of IgAN.

4.
Chinese Journal of Nephrology ; (12): 504-509, 2017.
Article in Chinese | WPRIM | ID: wpr-610923

ABSTRACT

Objective To evaluate the diagnostic value of clinical laboratory indexes on judgment of hypovolemia in the patients with nephrotic syndrome (NS).Methods The blood volume of each 50 cases of healthy adult men and women was assessed with indocyanine green-pulse dye densitometry (ICG-PDD).The normal range of blood volume and the cut-off value of hypovolemia were determined.The blood volume of 81 patients with NS was also measured with ICG-PDD and then these patients were divided into the hypovolemic group (21 cases) and the non-hypovolemic group (60 cases) according to the cut-off value of hypovolemia.The test data of clinical laboratory indexes of the patients in the two groups were compared,and the indexes with statistic difference were screened out.Their diagnostic values on judgment of hypovolemia were evaluated by receiver operating characteristic (ROC) curve analysis,and finally the indexes with high judgment accuracy were selected.Results ①The cut-off values of hypovolemia are < 52.9 ml/kg for the male and < 52.5 ml/kg for the women,which were determined with ICG-PDD.②The five clinical laboratory indexes,including orthostatic heart rate (OHR) increase > 10 bit per minute,fractional excretion of sodium (FENa) < 1,transtubular potassium gradient (TTKG) > 60%,blood urea nitrogen/serum creatinine ratio (BUN/Scr) > 20,and urine specific gravity (SG) > 1.020,were used to judge the hypovolemia in NS patients in this study.ROC curve analysis showed that the diagnostic accuracy in judgment of hypovolemia by one index or two indexes combination only belonged to medium level.However,the diagnostic accuracy in judgment of hypovolemia by the following three indexes combination,i.e.OHR increase+FeNa+BUN/Scr,FeNa+ BUN/Scr+SG,OHR increase+TFKG+BUN/Scr,or ORG increase+FeNa+TTTKG,reached high level.Conclusion This study obtained the cutoff value of Chinese adults hypovolemia are < 52.9 ml/kg for the male and < 52.5 ml/kg for the women,which are determined with ICG-PDD,through evaluation we recommend applying the above four specific combinations of three indexes for diagnosis of hypovolemia in NS patients.

5.
Chinese Journal of Nephrology ; (12): 410-415, 2017.
Article in Chinese | WPRIM | ID: wpr-617838

ABSTRACT

Objective To detect the level of serum α-klotho in different obese people and to investigate the correlation between serum α-klotho and obesity-related glomerulopathy (ORG).Methods A total of 48 cases of ORG diagnosed by renal biopsy were enrolled in the study.Fortyeight gender-,age-and BMI-matched obese participants,and 48 obese chronic kidney disease (CKD) patients without ORG were included as controls.The clinical manifestations,laboratory examinations of all three groups were collected,and the level of serum α-klotho protein was measured by ELISA.Results The patients with ORG were characterized by decreased serum α-klotho concentration compared with obese patients group and obese CKD patients group [572.66(439.92,690.58) pg/ml vs 635.85(559.52,769.20) pg/ml and 690.30(516.15,828.20) pg/ml,P< 0.01].Multinomial multiple logistic regression analysis revealed that serum α-klotho (per 100 pg/ml increased) was independently associated with the prevalence of ORG,and the risk of ORG decreased by 35% in the obese participants (OR=0.652,95% CI:0.487-0.872) and 38% in CKD patients (OR=0.617,95% CI:0.453-0.832) respectively.Conclusions The level of serum α-klotho is significantly decreased in ORG and associated with the prevalence of ORG independently.Serum α-klotho may be a protective factor for ORG.

6.
Chinese Journal of Laboratory Medicine ; (12): 873-875, 2016.
Article in Chinese | WPRIM | ID: wpr-508840

ABSTRACT

Over the past decade , with the rapid increase of the incidence of idiopathic membranous nephropathy (IMN) in our country, the diagnosis and treatment of IMN has been paid more and more attention.IMN is an autoimmune disease.Two important podocyte autoantigens , PLA2R and THSD7A, have been indentified sine 2009.Subsequently , serum anti-PLA2R antibody test and anti-THSD7A antibody test have also been used in clinical .Preliminary applications show that these two tests can not only help IMN diagnosis and differential diagnosis , but also help IMN prognosis.

7.
Chinese Journal of Laboratory Medicine ; (12): 901-905, 2016.
Article in Chinese | WPRIM | ID: wpr-508832

ABSTRACT

Objective This study was to observe the effects of different test conditions on the qualitative and quantitative detection of cryoglobulin .Methods We prepared 5 blood samples of different types of cryoglobulinemia . We detect the cryoglobulin qualitatively and quantitatively at different temperatures (37 ℃and room temperature of 20-25 ℃), and with different observation time (3 days and 7 days) and with different amount of blood (5 ml and 20 ml) .Further we will categorize the type of cryoglobulin and detect the components of cryoglobulin by immunofixation electrophoresis ( IFE) and other laboratory tests.Results (1) Blood samples from two groups were clotting and the serums were separated at 37 ℃ and room temperature respectively , and cryoglobulins of two groups were all qualitatively positive . Quantitative detection of cryoglobulins showed that the concentrations of cryoglobulins of room temperature group are lower than that of 37℃group;(2) Compared with 7 days, observing for only 3 days may lead to false-negative results in qualitative detection of cryoglobulin , and concentrations of cryoglobulin are also decreased;(3) Compared with 20 ml blood sample,5 ml blood sample is not enough for qualitative and quantitative detection of cryoglobulins .It may lead to false-negative results;(4) After purification, IFE and other laboratory tests can be used to categorize the types and find the components of cryoglobulins .Such examinations are helpful for finding the potential causes of cryoglobulinemia .Conclusions The positive of serum cryoglobulin is a key indicator of cryoglobulinemia .Detection of cryoglobulin can be affected by temperature, observed time and the blood volume for measurement .In addition, IFE and other laboratory tests are helpful for finding the type and the components of cryoglobulin .

8.
Chinese Journal of Nephrology ; (12): 140-144, 2015.
Article in Chinese | WPRIM | ID: wpr-469097

ABSTRACT

Objective To investigate the relationship of α-klotho protein and obesity related glomerulonephritis.Methods The chronic kidney disease (CKD) patients with or without ORG were diagnosed by renal biopsy.The normal and abdominal obesity control people were enrolled from the physical examination center.Propensity scoring analysis was done to balance the four groups of people in important clinical characteristics.The α-klotho levels in blood and urine were detected by ELISA.ORG mouse model was established and the mRNA and protein expression of klotho protein were detected by real-time quantitative PCR and Western blotting.Results (1) The plasma α-klotho levels decreased in ORG patients,CKD patients and abdominal obesity control people compared with normal control people [(251.7 ± 124.1) ng/L,(336.3 ± 126.1) ng/L,(377.1 ± 120.4) ng/L vs (472.3 ± 204.2)ng/L,all P < 0.05].The ORG patients had the lowest plasma α-klotho levels (P < 0.05).(2) ORG patients also had the lowest urine α-klotho levels compared with CKD patients,abdominal obesity and normal control people [(24.7±11.4) mg/mol vs (82.5±33.8) mg/mol,(74.5±32.5) mg/mol,(100.8±51.1)mg/mol,all P < 0.05].There was no difference in urine α-klotho levels of CKD patients,abdominal obesity and normal control people.(3) Compared with the normal control mouse,ORG model mouse showed decreased mRNA and protein expression of α-klotho protein in renal tissue.Conclusion The lower plasma and urine α-klotho levels in ORG patients may be due to the reduced expression of α -klotho protein in kidney.

9.
Chinese Journal of Nephrology ; (12): 919-924, 2014.
Article in Chinese | WPRIM | ID: wpr-458560

ABSTRACT

Objective To examine whether aldosterone contribute to obesity related glomerular disease. Methods C57BL/6J mice were randomly divided into three groups: a control group (low?fat?diet, n=10), a model group (high?fat?diet, n=10) and a intervention group (high?fat?diet, n=12). After 8 weeks intervention group were treated with a mineralocorticoid receptor antagonist, spirolactone (SPL).The physicochemical indexes and the renal pathology of the three groups were all detected. The mRNA and protein expressions of podocyte marker protein were determined by real?time PCR and Western blotting, respectively. Results Compared with the control group, body weight, kidney weight, Lee ’s index, fat index, blood cholesterol, blood triglyceride, creatinine clearance rate, urinary protein excretion, glomerular average diameter, glomerular foot process average width were significantly up ? regulated (P<0.05); The mRNA and protein expression of nephrin, podocin, podoplanin and podocalyxin were significantly down?regulated in model group (P<0.05). Meanwhile, these changes were attenuated by SPL. Conclusion Aldosterone can participate in the process of obesity? related renal injury, and these can be attenuated by mineralocorticoid receptor antagonist, spirolactone. This gives us preliminary clues to treat ORG.

10.
Chinese Journal of Nephrology ; (12): 222-225, 2012.
Article in Chinese | WPRIM | ID: wpr-428593

ABSTRACT

Objective To explore whether the glomerular podocytes can be damaged by aristolochic acid. Methods Thirty-two male SD rats were equally divided into the following 2 groups:model group in which the rats received the extract of Aristolochia manshuriensis Kom (AmK) by gavage; control group only received tap water by gavage.24 h urinary protein excretion was measured at the end of the 1st and 4th week,and SDS-PAGE gel electrophoresis was performed to detect the protein in urine.At the end of the 4th week,all the rats were sacrificed and the glomeruli were isolated by laser capture microdissection technique.The mRNA expression of nephrin,podocin,CDA2P,podocalyxin and podoplanin in isolated glomeruli was determined by RT-PCR,and the average width of glomerular foot process was measured by electron microscopy and image analysis. Results At the end of the 4th week,24 h urinary protein excretion in the model group was significantly higher than that in the control group (P<0.01) and the urinary albumin content in model group was also obviously increased.The average width of glomerular foot process in the model group was significantly larger than that in control group (P<0.01).The mRNA expressions of nephrin,podocin,CDA2P,podocalyxin and podoplanin in glomeruli were significantly down-regulated in the model group compared with the control group,which decreased by 34%,62%,56%,50%(P<0.01) and 27% (P<0.05),respectively. Conclusions Aristolochic acid can damage the glomerular podocytes,resulting in the down-regulation of nephrin,podocin,CD2AP,podoplanin and podocalyxin mRNA expression, the segmental widening of foot process, and increased urinary protein excretion.

11.
Chinese Journal of Nephrology ; (12): 720-724, 2012.
Article in Chinese | WPRIM | ID: wpr-424121

ABSTRACT

Objective To investigate the protective effects of Wnt-7a protein on renal interstitial fibrosis in mice of unilateral ureteral obstruction (UUO)model.Methods Eighteen male C57BL/6 mice were randomly divided into 3 groups:sham-operation group,the UUO model group and Wnt-7a treatment group.The body weight of mice was measured everyday.All the mice were sacrificed at thc seventh day after the operation.The left kidney was taken for histology evaluation and molecular biology assay.Masson's stain was performed as a main indicator of interstitial fibrosis.The expression of vimentin,α-smooth muscle actin,and E-adherin in renal tissue was detected by immunohistochemistry staining and the expression of α-smooth muscle actin and E-cadhe(nn) in renal tissue was detected by Western blotting.Results Compared with sham-operation group,body weight of the (,)odel group was significantly lower (P<0.05),and the relative area of interstitial fibrosis was significantly larger (P<0.05).Furthermore,the expression of vimentin and α-SMA was significantly up-regulated (P<0.05),and the expression of E-cadherin was significantly down-regulated (P<0.05).Compared with model group,all the above-mentioned abnormalities were restored to some extent and showed significant differences (P<0.05) in Wnt-7a treatment group.Conclusion Wnt-7a protein can decrease the interstitial fibrosis by inhibiting epithelial to mesenchymal transition in UUO mice.

12.
Journal of Peking University(Health Sciences) ; (6): 914-918, 2011.
Article in Chinese | WPRIM | ID: wpr-423845

ABSTRACT

SUMMARY A 15-year-old boy was admitted with nephritic and nephrotic syndrome,renal dysfunction and decreased serum C3,who suffered from varicella for two months.His renal histopathology revealed endocapillary proliferative glomerulonephritis with podocytes proliferation and severe tubular injury by light microscopy.Direct immunofluorescence showed global granular deposition of IgG,IgA,IgM,C3,Clq and fibrinogen in mesangium and along glomerular capillary wall.Electron microscopic examination showed electron-dense deposits in multiple sites of glomeruli.Furthermore,specific serum IgM antibodies against varicella-zoster virus (VZV) were detected.VZV antigen and mRNA were demonstrated in glomerular and tubular epithelial cells by immunohistochemical staining and in-situ hybridization.Virus particles and virus inclusions were identified by electron microscopy and special staining ( Methylene Blue and Eosion staining or Mann staining).The patient also experienced epileptic episodes and his brain MRI and electroenephalogram indicated herpes encephalitis with secondary epilepsy.Therefore,the diagnosis of VZV-associated glomerulonephritis and encephalitis was established.This is the first case of VZV-associated glomerulonephritis with renal histooathological evidence using in situ hybridization technique.

13.
Chinese Journal of Nephrology ; (12): 591-596, 2011.
Article in Chinese | WPRIM | ID: wpr-419647

ABSTRACT

Objective To investigate the effects of adiponectin on angiotensin Ⅱ-induced extracellular matrix production of mesangial cells(MCs) and its possible signaling pathway.Methods RT-PCR and indirect immunofluorescence examination were performed to detect the adiponectin receptors in MCs.Quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA) were used to observe the effects of adiponectin on angiotensin Ⅱ-induced transforming growth factor β1(TGF-β1) and fibronectin production of MCs.Western blotting was used to measure the ratio of p-AMPK to total AMPK.Results(1)Adiponectin receptors 1 and 2 were found in MCs. (2)The up-regulated mRNA and protein expression of TGF-β1 and fibronectin in MCs induced with 10-7 mol/L angiotensin Ⅱ (Ang Ⅱ) was significantly inhibited by 10 mg/L adiponectin (P<0.05).(3)The p-AMPK/AMPK ratio was significantly increased after incubation with adiponectin for 15 min and 30 min(vs 0 min, P<0.05), which suggested that adiponectin could activate the AMPK signaling pathway in MCs.The activation of AMPK signaling pathway was blocked by 40 μmol/L compound C, a specific inhibitor of AMPK. (4)The inhibitory effects of adiponectinonangiotensin Ⅱ-upregulatedTGF-β1andfibronectinexpressioninMCswere significantly relieved by 40 μmol/L compound C (P<0.05).Conclusions There are adiponectin receptors 1 and 2 in MCs.Adiponectin has inhibitory effects on the angiotensin Ⅱ-upregulated TGF-β1and fibronectin expression in MCs.AMPK signaling pathway may play an important role in the effects of adiponectin above-mentioned.

14.
Chinese Journal of Nephrology ; (12): 422-426, 2010.
Article in Chinese | WPRIM | ID: wpr-383582

ABSTRACT

Objective To investigate the prevalence and risk factors of chronic kidney disease (CKD) in the general adult population in the Hulunbeir Prefecture, Inner Mongolia Autonomous Region where many minorities of north China live. Methods Sampling surveywas performed in the residents aged 20 years and older in the Hulunbeir Prefecture. All the investigated subjects were tested for urinary albumin to creatinine ratio (ACR); hematuria by microscopy of urinary sediment; and GFR estimated by modified MDRD equation for Chinese adults (eGFR). The related risk factors of CKD were also investigated. Results A total of 4522 subjects were enrolled in the study. The prevalence of albuminuria was 7.11%, hematuria was 2.64% and reduced eGFR [60 ml-min-1·(1.73 m2)-1] was 2.75%. The prevalence of hypertension was 38.90%; hyperglycemia 6.61%; hyperlipidemia 2.72%; increased waist 24.79% and metabolic syndrome 15.02%. After the subjects with combined microalbuminuria, hematuria and reduced eGFR were excluded, the prevalence of CKD was 12.95%. Logistic regression analysis and stratified analysis showed increased age, increased waist, elevated systolic pressure, hyperglycemia,hypertriglyceridemia and metabolic syndrome were independently associated with albuminuria;increased age, elevated systolic pressure and hyperglycemia were independently associated with reduced eGFR; increased age was independently associated with hematuria. Conclusions The prevalence of adult CKD is 12.95% in the Hulunbeir Prefecture, Inner Mongolia Autonomous Region. Independent risk factors of CKD include increased age, increased waist, hypertension,abnormal blood glucose or lipid, and metabolic syndrome.

15.
Chinese Journal of Nephrology ; (12): 578-581, 2010.
Article in Chinese | WPRIM | ID: wpr-383416

ABSTRACT

Objective To investigate the impact of metabolic syndrome(MS)on clinicopathology of IgA nephropathy(IgAN). Methods A total of 118 IgAN patients complicated with MS were enrolled in the study as IgAN-MS group. Then 118 IgAN patients of same age arrange without MS were randomly selected as IgAN-non-MS group.A comparative analysis of clinical and pathological data between these two groups was performed. Results The urine protein, serum creatinine, body mass index, mean arterial pressure, serum triglyceride, fasting blood glucose and serum uric acid in IgAN-MS group were all significantly higher than those in IgAN-non-MS group(P<0.05 or P<0.01). The serum HDL-C level in IgAN-MS group was significantly lower than that in IgAN-non-MS group(P<0.01). The percentages of patient with hypertension, abnormal glucose metabolism or abnormal lipid metabolism in IgAN-MS group were also significantly higher than those in IgAN-non-MS group(P <0.01). The glomerular and tubulointerstitial pathological changes in IgAN-MS group were significantly more severe than those in IgAN-non-MS group(P<0.01). There were significantly positive correlations between MS and urinary protein quantity, serum creatinine level, and glomerular damage index or tubulointerstitial damage index(P<0.01)by Spearman rank correlation analysis. Conclusion MS may be an important risk factor of IgAN progression.

16.
Chinese Journal of Nephrology ; (12): 122-127, 2009.
Article in Chinese | WPRIM | ID: wpr-381302

ABSTRACT

Objective To investigate the interference and associated mechanism of hnman tissue kallikrein (HK) gene on renal interstitial fibrosis in rats with 5/6 nephrectomy. Methods Human kallikrein cDNA was packed in a recombinant adeno-associated virus(rAAV)-based plasmid vector. The rAAV-HK was produced by transfection in 293 cells. Twenty-four male Wistsr rats were divided into sham operation and operation groups. The rats with 5/6 nephrectomy were randomly divided into simple operation, control and experiment groups. The rats in experiment group received single dose rAAV-HK via the tail vein with 1×1011 pfu. Before nephrectomy and every month after surgery until the rats were sacrificed, the caudal arterial pressure was measured using tail cuff blood pressure determinator. Three months after HK gene delivery, the rats were sacrificed. The expression of HK in rats was assessed by RT-PCR, Western blot and enzyme-linked immunosorbent assay (ELISA). The pathological changes of renal interstitium were evaluated by Masson stainning, and the distribution of bradykinin B2 receptor (BKB2R) and angiotensin Ⅱ typel receptor (ATIR) was examined by immunohistochemistry. The expressions of BKB2R, AT1R, p-MAPK protein in renal tissue were detected by Western blot. Results Three months after HK gene delivery, the systolic blood pressure of experiment group was significantly decreased compared with the control group [(163±13) nun Hg vs (217±16) mm Hg, P<0.01](1 mm Hg=0.133 kPa). Compared with sham rats, the rats in simple operation group and control group had much more renal interstitial collagen deposition and more serious fibrosis performance, but renal interstitial collagen deposition and fibrosis were significantly ameliorated in the rats of experiment group. In addition, the tubulointerstitial injury index of HK transgenic rats was significantly lower than that of the rats in control group (1.33±0.73 vs 3.01±0.62, P<0.01). Up-regnlating expression of bradykinn B2 receptor protein and down-regulating expression of AT1 receptor and p-MAPK protein were found in renal tissues of experimental group after three months (P<0.05). Conclusion HK gene delivery significantly alleviates renal interstitial fibrosis in rats with 5/6 nephrectomy through regulating the expression of bradykinin B2 receptor, AT1 receptor and p-MAPK in renal tissue.

17.
Chinese Journal of Nephrology ; (12): 261-264, 2009.
Article in Chinese | WPRIM | ID: wpr-380958

ABSTRACT

Objective To compare the clinicopathological features between two kinds of obesity-related glomerulopathy (ORG). Methods Twenty-three patients with obesity-associated glomerulomegaly (OB-GM) and 22 patients with obesity-associated focal and segmental glomerulosclerosis (OB-FSGS) diagnosed by renal biopsy during 1998 to 2008 in our center were enrolled in this study. A retrospective analysis of clinical and pathological data was carried out. Results (1) All the patients in these two groups were with abdominal obesity. Most of them were middle-aged male. There were no significant differences in gender, age, body mass index and waist circumference between these two groups (P>0.05). The mean course of disease in OB-FSGS group was significantly longer than that in OB-GM group[(21.7±29.7) vs (6.8±9.3) months,P<0.05]. (2) Metabolic syndrome was found in the most patients of these two groups, but there were no significant differences in the levels of serum glucose, triglycerides, HDL-cholesterul, uric acid and blood pressure between them(P>0.05). (3) The 24-hour urinary protein and Ser level in OB-FSGSgroup were significantly higher than those in OB-GM group[(2.49±1.58) vs (0.83±0.87) g/d, P<0.05; (102.09±25.07) vs (87.84±20.63) μmol/L, P<0.05]. The serum albumin level, creatinine clearance and urinary osmotic pressure in the former were significantly lower than those in the latter [(38.67±7.00) vs (44.05±3.55) g/L, P<0.01; (95.78±37.83) vs (128.72±31.20) ml/min, P<0.01; (678.72±91.76) vs (840.69±133.88) mmol/L, P<0.01]. (4) The mean glomerular diameters of both OB-FSGS group and OB-GM group were increased, whose difference was not significant [(204.3±23.1) vs (205.3±14.3) μm, P>0.05]. Conclusion There are significant differences in the mean course of disease, 24-h urinary protein excretion, serum albumin level and renal function between these two different kinds of ORG.

18.
Chinese Journal of Nephrology ; (12): 465-470, 2009.
Article in Chinese | WPRIM | ID: wpr-380943

ABSTRACT

Objective To investigate whether low-protein diet has protective effect on the progression of renal interstitial fibrosis in rats with cyclosporine A (CsA)-induced nephropathy. Methods Eighteen male Sprague-Dawley rats were randomly divided into three groups (6 rats in each group). The rats in control group (C group) received common diet; in model group (M group) low-salt diet; in intervention group (Ⅰ group) low-salt and low-protein diet. After diet adaptation period of one week, the rats in C group received subcutaneous injection of olive oil 1 mg/kg daily for 5 weeks, while M group and Ⅰ group subcutaneous injection of CsA (diluted into 25 g/L with olive oil) 1 ml/kg for 5 weeks. All the rats were sacrificed at the end of the 5th week. The food-intake and body weight were measured daily. The creatinine clearance (Ccr) was examined before rats were sacrificed. The semi-quantitative pathological analysis on kidney sections was performed. The mRNA and protein expression of transforming growth factor-β1 (TGF-βI) and type Ⅰ collagen (Col Ⅰ) in kidney tissue was determined with real time PCR and immunohistochemical staining, respectively. Results The food-intake and body weight of rats in M and I groups were significantly lower than those in C group (P<0.05). Compared with C group, the Ccr levels in M and Ⅰ groups were significantly reduced [(0.65±0.15) ml/min, (0.40+0.13) ml/min vs (1.55±0.29) ml/min, P<0.05], the relative fibrosis areas of kidney interstitium in M and I groups were significantly increased (3.60%±0.46%, 3.26%±0.75% vs 0.44%±0.24%, P<0.05), the mRNA and protein expression of TGF-β1 in M and I group was significantly up-regulated (by 2.6 and 3.1 times in mRNA and by 1.5 and 1.6 times in protein, respectively, P<0.05), and the mRNA and protein expression of Col Ⅰ in M and I groups was also significantly up-regulated (by 3.0 and 3.5 times in mRNA and by 2.3 and 2.1 times in protein, respectively, P<0.05). There were no significant differences between M and I groups in every parameters above-mentioned except the rat body weight and Ccr. Both the body weight and Ccr in Ⅰ group were significantly lower than those in M group (P<0.05). Compared with C group, the urine osmotic pressure in M group and in I group were deceased (for M group, P>0.05; for I group, P<0.05). Compared with C group, the serum cholesterol levels in M and I groups were significantly increased (P<0.05), and the serum phosphorus level in I group was significantly decreased (P<0.05). The levels of serum albumin and serum calcium of all three groups had no statistical differences (P>0.05). Conclusion Low-protein diet has no renoprutective effects on the rat model of cyclosporin A nephropathy, on the contrary, may induce body weight loss.

19.
Chinese Journal of Nephrology ; (12): 925-929, 2009.
Article in Chinese | WPRIM | ID: wpr-380378

ABSTRACT

Objective To study the pathogenesis of anemia in chronic aristolochic acid nephmpathy(CAAN) rats. Methods The hemoglobin(Hb)values of sixty-two male SD rats were assayed to determine its normal range.Among them,24 rats with normal Hb value were randomly divided into 2 groups:model group (MG)in which rats received the extract of Aristololochia manshuriensis Kom (AmK) by gavage,and control group (CG) received tap water only by gavage.Body weisht(BW),Hb,24 h urinary protein excretion(UP)and creatinine clearance (Ccr)of 6 rats in each group were measured before administration and at the end of the 8th week, respeetively.then these rats were sacrificed.The relative area of renal interstitial fibrosis was measured by microscopy.The mRNA expression of erythropoietin (EPO)in kidney tissue Was determined by real-time RT-PCR;protein expression of type I collagen(Coll),aminopeptidase P (APP),hypoxia indHeible factor let and 2α(HIF-1α and HIF-2α)in kidney tissue Was examined by immunohistochemistry staining. Results Hb values of normal rats presented normal distribution. The normal Hb was (155.9±16.5) g/L. Rat anemia was diagnosed when Hb was below 123.6 g/L. There was no difference in all the examination results between CG and MG before administration (P>0.05). Compared with CG, the Hb and Cer in MG were significantly decreased [(121.66±15.68) g/L vs (169.00±12.89) g/L, (0.63±0.13) ml/min vs (1.27±0.18) ml/min, P< 0.01], and the UP in MG was significantly increased at the end of the 8th week [(27.04±9.40) mg/d vs (6.11±0.84) mg/d, P<0.01]; the relative areas of fibrosis and Col l in renal interstitium of MG were significantly enlarged [(12.89±2.33)% vs (0.55±0.10)%, (13.92±2.92)% vs (1.32±0.84)%, P<0.01]; the protein expression of APP and the mRNA expression of EPO in the kidney tissue of MG were significantly down-regulated [(0.55±0.23)% vs (3.77±1.06)%, 0.005±0.001 vs 0.032±0.013, P<0.01]; the protein expression of HIF-lα and HIF-2α in the kidney tissue of MG was significantly up-regulated (2.55±0.16 vs 1.12±0.46, 2.33±0.33 vs 1.15±0.27, P<0.01), at the end of the 8th week. Conclusions The pathogenesis of anemia in CAAN may be due to the decreased production of EPO caused by the destruction of peritubular capillary. The compensatory up-regulation of HIF-lα and HIF-2α expression can not prevent the anemia development.

20.
Chinese Journal of Nephrology ; (12): 901-905, 2009.
Article in Chinese | WPRIM | ID: wpr-380242

ABSTRACT

Objective To introduce a case of varicella.zoster virus(VZV)-related glomerulonephritis and encephalitis. Methods The clinical data and renal pathology were analyzed.Associated literatures were reviewed. Results A 15 years old male patient presented nephritic syndrome,nephrotic syndrome and renal dysfunction with reduced serum complement C3 level from the 5th day after he suffered from varicella.The pathological diagnosis of his kidney tissue was endocapillary proliferative glomerulonephritis with podocyte proliferation and severe renal tubular injury by light microscopy.Immunofluorescent and electron microscopic examinations showed "full-house"staining and granular electron-dense deposits in multiple sites.respectively. Furthermore.virus-like particles or/and inclusions could also be seen by electron microscopy and Mann staining light microscopy.Positive varicella-zoster virus (VZV) specific lgM antibody was detected by serum virological test.VZV antigen and RNA transcript were found in glomerular and tubular cells by immunohistochemical staining and in situ hybridization of renal tissues,respectively. The patient had epileptic episodes for many times in his disease course and his brain MRI and electroencephalogram findings accorded with viml encephalitis with secondary epilepsy.So,the diagnosis of VZV-related glomerulonephritis and encephalitis was established. Conclusion This is the first report of VZV-related glomerulonephritis and encephalitis confirmed by serum virology and tissue virology.

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