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OBJECTIVE：To study the improvement effect and possible mechanism of Leontopodium leontopodioides combined with Astragalus membranaceus on the renal function of mesangial proliferative glomerulonephritis （MsPGN） model rats. METHODS：Totally 85 rats were randomly divided into sham operation group （n＝10）and modeling group （n＝75）. Sham operation group underwent sham operation ，and MsPGN model was induced by immunological method [Freund ’s adjuvant+BSA + lipopolysaccharide（LPS）] in modeling group. After successfully modeling ，70 rats were randomly divided into model group ，L. leontopodioides+A. membranaceus high-dose，medium-dose and low-dose groups （4.05，2.03，1.02 g/kg，by total crude drug ），L. leontopodioides alone group （2.70 g/kg，by crude drug ），Tripterygium glycosides tablet group （positive control 1，0.02 g/kg）， Lotensin tablet group （positive control 2，0.02 g/kg），with 10 rats in each group. Sham operation group and model group were given constant volume of normal saline intragastrically ； administration groups were given relevant drug solution intrasgastrcially at a volume of 15 mL/kg，once a day ，for consecutive 5 weeks. At last administration ，24 h urinary lnzyxyqy2003@163.com protein，urine creatinine and serum creatinine were determined in rats. The right kidney was weighed ，and HE staining was used to observe the pathomorpholog y changes of renal tissue. Immunohistochemistry was used to detect the protein expression of NF-κB p65 in renal tissue. Western blotting assay was used to determine the protein expressions of NF-κB p65，IκBα，ERK，p-ERK and p 38 MAPK in renal tissue. RESULTS ：Compared with sham operation group ，right kidney weight ，24 h urine protein and serum creatinine levels ，protein expressions of NF-κB p65， p-ERK and p 38 MAPK in renal tissue were increased significantly in model group （P＜0.05 or P＜0.01）；the level of urine creatinine and protein expression of IκBα in renal tissue were decreased significantly（P＜0.05 or P＜0.01）；there were obvious glomerular hypertrophy ，diffuse increase of mesangial cells ，necrosis of renal tubules and other pathomorphological changes in renal tissue. Compared with model group ，right kidney weight and serum creatinine level were decreased significantly in L. leontopodioides alone group （P＜0.05），while urine creatinine level was increased significantly （P＜0.05），but there was no statistical significance in the level of 24 h urine protein （P＞0.05）；the right kidney weight ，24 h urine protein ，serum creatinine level and protein expression levels of NF-κB p65，p-ERK and p38 MAPK in renal tissue were decreased significantly in L. leontopodioides+A. membranaceus high-dose group （P＜0.05），while the urine creatinine level and protein expression level of IκBα in renal tissue were increased significantly （P＜0.05 or P＜0.01）；there was no statistical significance in above indexes in L. leontopodioides+A. membranaceus medium-dose，low-dose groups （P＞0.05）；pathological changes of renal tissue were improved to different extents in administration groups ，especially in L. leontopodioides +A. membranaceus high-dose group. CONCLUSIONS ： High dose of L. leontopodioides +A. membranaceus can improve renal function of MsPGN model rats by inhibiting MAPK/NF-κB signal pathway.
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Background: Idiopathic nephrotic syndrome (INS) is a common childhood renal disease characterized by a remitting and relapsing course, associated with different histopathological subtypes. The true incidence of various histopathological subtypes of NS remains under estimated owing to the diversity in indication criteria for performing renal biopsies in pediatric population.Methods: This was a cross-sectional observational study in children with nephrotic syndrome at a tertiary health care centre. Total 22 children, with nephrotic syndrome, who underwent renal biopsy procedure during a period of one year, were enrolled for the study. Indications of renal biopsy were noted, and the histopathology reports were studied in detail.Results: In this study group, the most common indication for renal biopsy was 'Atypical age (> 8years) of diagnosis in 45.5% (10/22) patients, followed by 22.7% (5/22) in 'Children presenting with hypertension and hematuria'.The most common histopathological finding in these children was mesangial proliferative glomerulonephritis in 45.5% (10/22) patients followed by IgA nephropathy with mesangial proliferation in 22.72% (5/22) and minimal change disease in only 13.6% (3/22).Conclusions: This study highlights the occurrence of non-MCD as the common cause of INS in the children and denotes the significance of performing renal biopsies in children with INS for better prognostication.
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Objective:To explore the clinical correlation of HLA-DRB1 shared epitope with IgA mesangial proliferative glomer-ulonephritis( IgA MsPGN).Methods:The renal function were examined routinely,and HLA-DRB1 shared epitope were determined by PCR in a total of 164 patients with IgA MsPGN and 164 healthy subjects.The renal function and HLA-DRB1 shared epitope were compared in patients with IgA MsPGN and healthy subjects,and clinical correlation of HLA-DRB1 shared epitope and renal function were analyzed.Results:(1)24 h proteinuria,serum creatinine and serum urea nitrogen were significantly different in patients with IgA MsPGN and healthy subjects(P<0.01);(2)The high-frequency gene of HLA-DRB1 in patients with IgA MsPGN were DRB1*04, DRB1*07,DRB1*09,DRB1*11,DRB1*14 and DRB1*15;(3) The distribution frequency of DRB1*09 and DRB1*11 in patients with IgA MsPGN increased significantly(P<0.01 or P<0.05);(4)24 h proteinuria,serum creatinine and serum urea nitrogen in patients with IgA MsPGN with DRB1*09 and DRB1*11 were significantly different compared with those in patients with IgA MsPGN with other HLA-DRB1 shared epitope(P<0.01).Conclusion:HLA-DRB1 shared epitope is related to IgA MsPGN,DRB1*09 and DRB1*11 can increase the risk of IgA MsPGN,and related to the severity of glomerulonephritis.
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Objective] To explore both the correlation of matrix metal oproteinase and the imbalance of its tissue inhibitors-MMP-2 and TIMP-2 with glomerulosclerosis and its research progress in traditional Chinese medicine. [Methods] We generalized the research progress in traditional Chinese medicine from such aspects as the biological properties of MMP-2 and TMIP-2 and their mechanisms, their relationship with mesangial proliferative glomerulonephritis and effects of traditional Chinese medicine on their expression by searching the relevant literatures. [Results] Expressions of MMP-2 and TIMP-2 vary in different pathological stages(hyperplasia and sclerosis stage here) of glomerulonephritis, and traditional Chinese herbs could adjust their expressions in different stages. Traditional Chinese herbs can inhibit the development of glomerulosclerosis. [Conclusion] Applying traditional Chinese medicine in the treatment of mesangialproliferative glomerulonephritis could provide the base for further development of TCM as wel as a new choice for treating mesangialproliferative glomerulonephritis.
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Objective To analyze cases diagnosed with glomerular minor lesion (GML) by light microscopy and immunofluorescence,uncover their final pathology diagnosis by electron microscopy,and thereby clarify the pathological and clinical meaning of GML.Methods One hundred and forty-eight patients receiving renal biopsy between 2003 and 2008 in Peking Union Medical College Hospital,with diagnosis of GML described by light microscopy and immunofluorescence examination were retrospectively studied.All the clinical data and pathological observation were collected and analyzed,including intact results of electron microscopic examination which were considered as golden standards of pathological diagnosis.Results The 148 patients with GML had heterogenous clinical features,with isolated hematuria as the most common presentation.Electron microscopy revealed various pathological presentations:thin basement membrane nephropathy (TBMN,66.2％),mesangial proliferative glomerulonephritis (MsPGN,20.3％),Alport syndrome (2.7％),membranous nephropathy (MN,3.4％),normal tissue (4.7％).Among GML patients with isolated hematuria,TBMN ranked as the most common pathology (76.9％).Conclusions GML is only an equivocal description of pathological manifestation by light microscopy and immunofluorescence examination.And electron microscopy is necessary to obtain accurate pathology diagnosis for patients undergoing renal biopsies.
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10.3969/j.issn.1000-3606.2013.06.020
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Objective To understand the differences between sexes in the clinical and pathological features of patients with mesangial proliferative glomerulonephritis(MPGS).MethodsOne hundred and five patients with MPGS admitted to our hospital were retrospectively studied in clinical and pathological aspects.Results( 1 ) The proportion of male patients were 75 of 105 ( 71.43 ％ ) and that of females were 30 of 105 ( 28.57％ ) ; ( 2 ) The average age of the male patients was ( 40.25 ± 15.50 ) and that of the females was (36.23 ± 15.26) in year.There was no significant difference between the two groups( t =1.206,P =0.231 ) ;(3) There was no significant difference in duration of disease,hematuria,edema,hypertension prevalence and mean blood pressure( P ＞ 0.05 ).The proportion of patients with hematuria was 56.19％ (59/105).The males accounted for 69.33％ ( 52/75 ) and the females were 63.33％ ( 19/30 ) in the main clinical manifestations of nephrotic syndrome.There was no significant difference( x2 =0.352,P ＞ 0.05 ) between the proportion of males and females; (4)Males and females groups had no significant difference( P ＞ 0.05 )on levels of urinary protein,serum albumin,immunoglobulin,complement,urea nitrogen and serum creatinine.Complement decreased in 53 cases,accounting for 53％ of all the participants.The proportion of male patients with renal insufficiency was 24.00％ (18/75),and the proportion of females with renal insufficiency was 13.33％ (4/30).There was no significant difference ( x2 =1.472,P ＞ 0.05 )on the percentage of males and females with renal insufficiency.The mean value of urea nitrogen was higher than the normal levels ; (5) The proportion of male cases with different deposition of immune complexes was 93.06％ (67/72),and the proportion in females were 92.86％ (26/28) in the exception of 5 cases ( male 3 and female 2 ) with no glomeruli in immunofluorescence examination.No significant difference was found between the two groups( x2 =0.001,P ＞ 0.05 ) ; ( 6 ) There was no significant gender differences( x2 =1.696,P ＞ 0.05 ) found in risk assessment.ConclusionThe prevalence of MPGS is higher in male patients than in females,the main clinical manifestations of which were nephrotic syndrome.Patients were found to have a higher rate of hematuria,decreased complement C3,and renal dysfunction than the normal levels.There was no significant difference in gender on the clinical and pathological aspects of MPGS.
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Background: Immunoglobulin M nephropathy (IgMN) is an idiopathic glomerulonephritis (GN) usually presenting clinically as steroid resistant/dependent nephrotic syndrome (NS) with pathology of mesangial proliferative GN or focal and segmental glomerulosclerosis with diffuse predominant mesangial IgM deposits. Not much information is available about its natural history. This is the first Indian study to our knowledge on IgMN in adults and adolescents. Materials and Methods: We evaluated renal biopsies performed at our center between January,'04 to September,'09. Biopsies of all adolescents and adults were evaluated for IgMN and we studied their age, gender distribution, blood pressure (BP), disease duration, steroid/immunosuppressive management and serial serum creatinine (SCr), urinary proteins, and BP values. Patients with other systemic diseases/infections and children were excluded. Results: IgMN constituted 4.3% of 2702 adult renal biopsies. No significant gender predilection was noted. Males presented at average age of 23.1 years, females at 30 years. Steroid-dependent NS was the commonest presentation noted in 75% followed by steroid-resistant NS. Hypertension was noted in 10% patients. Mesangial proliferative GN (MePGN) was commonest histopathological finding noted in 74.4%, followed by focal segmental glomerulosclerosis (FSGS) in 16.2%, and minimal change disease (MCD) in 9.4% biopsies. Sole IgM deposits were noted in 88.5%. All MCD, 35.6% MePGN reached remission, FSGS progressed to renal failure by 1 year. Hypertension, proteinuria, interstitial fibrosis, and FSGS were bad prognosticators. Conclusions: This is the first Indian study of IgMN in adults and adolescents carried out over a period of 5.8 years, which has shown that hypertension, proteinuria, and interstitial fibrosis at presentation have bad prognosis.
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Adolescent , Adult , Aged , Biopsy , Female , Glomerulonephritis/chemically induced , Glomerulonephritis/epidemiology , Humans , Immunoglobulin M/toxicity , India/epidemiology , Kidney/pathology , Male , Middle Aged , Prevalence , Risk Factors , Young AdultABSTRACT
OBJECTIVES: To document the histopathological spectrum of atypical nephrotic syndrome in Jamaican children and to make clinicopathological correlations which will assist physicians in identifying patients needing nephrology consultation. METHODS: This was a retrospective review of renal biopsy data of Jamaican children who were referred to the University Hospital of the West Indies and the Bustamante Hospital for Children between January 1985 and December 2008. The study population consisted of children < 12 years old with atypical nephrotic syndrome. RESULTS: Biopsies were done in 157 children - 85 males and 72 females (mean age 8.91 ± 3.44 years). Indications for biopsy were steroid resistance (35%), frequent relapses (8.9%) and other atypical presentations (56.1%). Overall, mesangial proliferative glomerulonephritis (MesGN) was the commonest histology (49/157, 31.2%), followed by minimal change disease (MCD) (36/157, 22.9%) and diffuse proliferative glomerulonephritis (DPGN) (26/157, 16.6%). Infection was present in 38/157 (24%) cases. Diffuse proli ferative glomerulonephritis was the predominant type associated with streptococcal infection (52.9%) while Hepatitis B was seen in 83% ofcases ofmembranous nephropathy. CONCLUSION: Mesangial proliferative glomerulonephritis is the commonest histology seen in Jamaican children with atypical nephrotic syndrome. Most membranous nephropathy is Hepatitis B related. Hypertension with hypocomplementaemia, renal failure and anaemia are features ofmore serious renal disease (eg membranoproliferative glomerulonephritis and crescentic nephritis) rather than MCNS and should warrant urgent nephrology consultation for renal biopsy.
OBJETIVOS: Documentar el espectro histopatológico del síndrome nefrótico atípico en los niños jamaicanos y hacer correlaciones clínico-patológicas que ayuden a los médicos a identificar pacientes que necesitan la consulta de nefrología.. MÉTODOS: Se trata de un estudio retrospectivo de datos de biopsias renales de niños jamaicanos remitidos al Hospital Universitario de West Indies y al Hospital Pediátrico Bustamante, entre enero de 1985 y diciembre de 2008. La población del estudio consistió en niños < 12 años de edad que padecían el síndrome nefrótico atípico. RESULTADOS: Se realizaron biopsias a 157 niños - 85 varones y 72 hembras (edad promedio 8.91 + 3.44 años). Las indicaciones para la biopsia se debieron a resistencia a los esteroides (35%), recaídas frecuentes (8.9%) y otras manifestaciones atípicas (56.1%). En general, la glomerulonefritis proliferativa mesangial (GNMes) fue la histología más común con 49/157 (31.2%), seguida por la enfermedad de cambio mínimo (ECM) con 36/157(22.9%) y la glomerulonefritis proliferativa difusa (GNPD) con 26/157 (16.6%). La infección estuvo presente en 38/157 (24%) de los casos. La glomerulonefritis proliferativa difusa fue el tipo predominante asociado con la infección estreptocóccica (52.9%), mientras que Hepatitis B fue observada en el 83% de los casos de nefropatía membranosa. CONCLUSIÓN: La glomerulonefritis proliferativa mesangial es la histología que con mayor frecuencia se observa en los niños jamaicanos que padecen el síndrome nefrótico atípico. La mayoría de los casos de nefropatía membranosa guardan relación con la hepatitis B. La hipertensión con hipocomplementemia, la insuficiencia renal y la anemia son rasgos más bien de enfermedades renales más serias (p.ej, glomerulonefritis membranoproliferativa, nefritis crescéntica) que del síndrome nefrótico de cambios mínimos (SNCM) y debe asegurarse la consulta urgente con el nefrólogo para se realice una biopsia renal.
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Child , Child, Preschool , Female , Humans , Male , Kidney/pathology , Nephrotic Syndrome/pathology , Glomerulonephritis, Membranoproliferative/pathology , Glomerulonephritis, Membranous/microbiology , Glomerulonephritis, Membranous/pathology , Jamaica , Nephrosis, Lipoid/pathology , Streptococcal Infections/pathologyABSTRACT
Mesangial proliferation is a basic pathologic process of many kidney diseases,mesangial proliferative glomerulonephritis(MsPGN) is the common pathological type.The pathogenesis of MsPGN still remains unclear.Recently,cytokines of fractalkine,interleukin and TGF-β gradually become hotspot in the pathogenesis of MsPGN.Studies shows that a variety of cytokines play an important roles in the development of MsPGN and the mechanism has been gradually clarified.Certain progress has been made in treatment,and more profound understanding of mycophenolate mofetil has been received,the treatment of the MsPGN as manifestations with refractory nephrotic syndrome has been achieved good effect.This review is based on the recent years of the primary non-IgA MsPGN progress.
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Objective To investigate the association of HLA-DRB1 alleles in Han population of Shanxi childrcn with nephrotic syndrome of non-IgA mesangial proliferative glomerulonephritis (MsPGN). Methods HLA-DRB1 was performed by polymerase chain reaction-sequence specific primers technique, and twenty patients with nephrotic syndrome of non-IgA MsPGN were detected. Results Analysis of the fre- quencies of specific at the HLA-DRB1 loci revealed significantly higher frequencies of HLA-DRB1 * 11 al- leles among the nephrotic syndrome patients of non-IgA MsPGN comparing with controls (22. 50% vs 8.33%, x2= 9. 544, P = 0.002, CI = 1. 674-9.995, RR = 4.09). Nine patients with HLA-DRB1 * 11 all accompanied hematuria, hypertension or short renal insufficiency. Conclusion The results suggested that HLA-DRB1 * 11 alleles contribute to genetic susceptibility to nephritic syndrome of non-IgA MsPGN. The pa- tients with HLA-DRB1 *11 easy accompanied hematuria, hypertension or short renal insufficiency.
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Objective: To investigate the mechanism of Shenyankang(肾炎康) on rats with mesangial proliferative glomerulonephritis(MsPGN).Methods: MsPGN rat model was induced by chronic(serum-sickness).Six weeks later,MsPGN rats were given 3 ml of Shenyankang oral liquor every day(Shenyankang oral liquor treated group) or 3 ml of water every day(model group).Forty-two days after(using) the drug,urine protein(UP) of 24 hours,renal function and urine level of tumor necrosis factor?(TNF?) and endothelin1(ET1) were evaluated.Pathologic changes of renal tissue were observed by microscopy.Results: Compared to the normal control group,UP of 24 hours,blood urea nitrogen(BUN), serum creatinine(SCr) and urine level of TNF? and ET1 increased significantly in model group((all P
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Objective To investigate the change of oxidation system and antioxidation system in mesangial proliferative glomerulonephritis(MsPGN) induced by anti-Thy1.1 antibody,and further to study the intervention of rosmarinic acid(RAD).Methods Anti-THy1.1 serum was produced,and then intravenously injected into rats for establishing an experimental model of MsPGN.The experiment was designed for control with or without RAD,glomerulonephritis with or without RAD,respectively.The activity of superoxide dismutase(SOD) and the content of malondialdehyde(MDA) in tissue homogenate were detected by spectrophotomerty.Results The activity of SOD significantly decreased,while the content of MDA increased in MsPGN.RAD could inhibit oxidation in the mesangial cells.Conclusion Lipid peroxidation participates in MsPGN and RAD can control the changes of the mesangial cells and show the activity of antioxidation.
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Objective:To investigate the expression of mmp-2 in mesangial proliferative glomerulonephritis(MsPGN) rat renal tissue and the effects of nourishing kidney and activating blood flow recipe of TCM. Methods: 54 Male SD rats were divided into control group, MsPGN group and treatment group with nourishing kidney and activating blood flow recipe of TCM. Immunohistochemical staining, flow cytometry, western blot and RT-PCR were used to check the protein expression of mmp-2. Results: In MsPGN group, following with the disease progressing, the glomerulus grew graduatly, ECM increased, the basement membrane of glomerulus was thicker. The immunohistochemical staining showed that the chief positive granules were deposited in glomerulus and renal tubular, the expression of mmp-2 was lower than that in control group, but in treatment group the expression of mmp-2 was higher than that in MsPGN group. Conclusion: In MsPGN renal tissue, the expression of mmp-2 was reduced, its activity was weakened. Nourishing kidney and activating blood flow recipe of TCM could induce the expression of MMP-2 and partly recover the activity. Nourishing kidney and activating blood flow recipe of TCM could resist glomerular sclerosis and postpone the course of chronic renal failure.
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Objective:To investigate the expression of matrix metalloproteinase(MMP) and tissue inhibitor of matrix metalloproteinase(TIMP)in mesangial proliferative glomerulonephritis(MsPGN) rat renal tissue and the effects of nourishing kidney and activing blood recipe of traditional Chinese medicine.Methods:Chose 54 male rats and separated them into control group, MsPGN group and treated group with nourishing kidney and activing blood recipe of traditional Chinese medicine.Chose six rats per group at the time of the second,the fourth and the eighth week.The sections were treated with HE and PAS stains and the routine pathologic study was carried.Immunohistochemical staining was used to check the expression of MMP-2,TIMP-2, membrance type metalloproteinases-1(MT1-MMP) and transforming growth factor-?1(TGF-?1).Flow Cytometry was used to check the protein expression of MMP-2,TIMP-2,MT1-MMP and TGF-?1 in rat renal tissue.Results:In MsPGN group,following with the disease progressing,the glomerulus grew graduatly,ECM became more and more,the basement membrane of glomerulus was thicker.The immunohistochemical staining showed the expression of MMP-2 and MT1-MMP was lower compared with control group,but in treated group the level was weaker,the expression of TIMP-2 and TGF-?1 was higher compared with control group,but in treated group the level was weaker too. At the fourth and the eighth week, the Flow Cytometry showed that in MsPGN group the FI of MMP-2 was lower compared with control group(P
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Objective To investigate the correlation between cytotoxic T lymphocyte associated antigen 4 (CTLA - 4 ) and primary nephrotic sysdrome(PNS) with the pathologic type of mesangial proliferative glomerulonephritis(MsPGN) of glucocorticoid(GC) resistance. Methods The polymerase chain reaction - restriction fragment length polymorphism( PCR - RFLP) analysis was used to investigate the genotype of position - 318 promoter of CTLA- 4 gene of 36 patient children and 30 healthy controls. Results The frequences of genotypes at position - 318 promoter of CTLA- 4 gene in patients were 38.9% for CC,61.1 % for TC and 0% for TT. The frequences of alleles at this position were 69.4% for C allele and 30.6% for T allele. The frequences of genotypes and alleles in children were not significantly different from those in controls. Conclusion CTLA-4 promoter ( -318)C/T dimorphism was not associated with PNS- MsPGN of GC resistance, which hinted that the polymorphism may be not inlolved in pathogenensis of PNS-MsPGN and the mechanism of GC resistance.
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Objective To observe P27 expression and proliferation of mesangial cells of rats with Thy1 glomerulonephritis and to evaluate the interfering effect of valsartan, a specific angiotensin Ⅱ receptor antagonist, on Thy1 glomerulonephritis. Methods Rats were divided into normal control group, Thy1 glomerulonephritis group and valsartan treatment group. Following the onset of glomerulonephritis, renal morphological changes were observed on days 1, 3, 5 and 7, and proliferating cell nuclear antigen(PCNA) and P27 expression in glomerulus were measured by immunohistochemistry and Western blotting. Results High expression of P27 was found in quiescent mesangial cells of normal rats, but decreased expression in mesangial cells of rats with Thy1 glomerulonephritis, accompanying with the proliferation of mesangial cells. In valsartan treatment group, glomerular hypercellularity, mesangial matrix expansion and PCNA expression were significantly reduced as compared with those of the untreated rats with Thy1 glomerulonephritis from day 3 to day 7( P
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Objective To investigate the mechanism of Bushen Huoxue Recipe (Recipe to reinforce the kidney and activate blood) in the treatment of glomerulosclerosis of the rats with mesangial proliferative glomerulonephritis (MsPGN).Methods Fifty-four SD male rats were randomized into normal group, model group, and treated group with 18 rats in each. The MsPGN models were made by injection of anti-rat-thymocyte antiserum (ATS) through the tail vein. After modeling, the treated group was administered Bushen Huoxue Recipe with a dosage of 5ml/kg, once a day. Six rats from each group were selected in the second, fourth, and eighth week respectively to determine the content of urine protein (Upro), blood urea nitrogen (BUN), and serum creatinine (SCr), and the kidney was cut for pathological observation and immunohistochemical detection of the kidney tissues, the expression of Ⅳ-type collagen (Col-Ⅳ) and laminin (LN).Results The pathological determination showed that, at the same time points, the hyperplasia of mesangial cells in the treated group was significantly relieved and mesangial matrix reduced as compared with the model group. The content of Upro, BUN and SCr at all time points in the treated group was significantly decreased as compared with the model group (P