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Objective·To investigate the effect of glycoprotein 130 (GP130) inhibitor SC144 on extracellular matrix accumulation and JAK2/STAT3 signaling pathway in unilateral ureteral obstruction (UUO) mouse model, and explore its mechanism. Methods·Eighteen female BALB/c mice were randomly divided into 3 groups i.e. sham group, UUO group and SC144 group. All mice were sacrificed at day 14 and kidneys were harvested for further analysis. The changes of renal tissue morphology and pathology were observed by H-E and Masson staining. The expression of α-smooth muscle actin (α-SMA) and infiltration of macrophage cells were assayed by immunohistochemical staining. The levels of collagen-I, collagen-IV, monocyte chemoattractant protein-1(MCP-1),transforming growth factor-β(TGF-β)mRNA were analyzed by real-time PCR.The activation of JAK2 and STAT3 was measured by Western blotting. Results·There was a trend toward decreased renal tubular lesion and renal interstitial fibrosis in SC144 group (H-E, P=0.052;Masson,P=0.063).SC144 significantly inhibited the levels of α-SMA,type I/type IV collagen and TGF-β mRNA(all P<0.05).Compared with UUO group, the phosphorylation levels of JAK2 and STAT3 were significantly decreased in SC144 group (both P<0.05). Conclusion·The treatment of UUO mouse model with SC144 can inhibit the activation of α-SMA, attenuate the phosphorylation of STAT3, reduce extracellular matrix protein deposition following injury and renal tubular epithelial-mesenchymal transition(EMT)via JAK2/STAT3 signaling pathway,indicating its potential in attenuating interstitial fibrosis in obstructive nephropathy.
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Objective To evaluate the clinical features of primary vesicoureteral reflux(VUR) in children and to investigate the association of sex,age,reflux grade and renal parenchymal damage (RPD) in VUR.Methods Medical records of 85 patients in Department of Pediatric Nephrology,Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine diagnosis as VUR from Jan.2000 to May 2012 were reviewed.VUR was diagnosed by voiding cystourethrogram(VCUG).According to the results of VCUG,patients were divided into groups of low-grade(Ⅰ-Ⅱ)VUR and high-grade (Ⅲ-Ⅴ) VUR.All cases underwent Tc-dimercaptosuccimc acid (DMSA) renal scan,RPD was defined by image appearance and relative kidney uptake.The impact of patient's gender and age as well as VUR grade on RPD were compared.Results A total of 85 patients (33 boys,52 girls) were included,of whom 59 cases (69.4％)were under 2 years old,26 cases(30.6％) were older than 2 years.VUR was unilateral in 45 patients(52.9％) and bilateral in 40 patients(47.1％),total of 125 renal units.The high-grade VUR was 93 renal units(74.4％),the incidence of high-grade VUR was significantly higher in patients who under 2 years old,but the reflux grade showed no association with gender.RPD was found in 89 renal units(71.2％).RPD rate was associated with high-grade reflux (P =0.030),male gender (P=0.021)and age(P =0.005).Conclusions The high-grade VUR is common seen in patients under 2 years old.The risk of RPD in patients were under 2 years old and in boys.High-grade VUR is a critical risk factor of RPD in children.
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<p><b>OBJECTIVE</b>To study the expression of transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF) in kidney tissues of children with primary focal segmental glomerular sclerosis (FSGS) and the possible role of the two growth factors in the development of FSGS.</p><p><b>METHODS</b>Kidney specimens were obtained from 33 children with primary FSGS and 7 children with isolated haematuria but without FSGS (control group). Of the 33 children with primary FSGS, 6 children had no renal tubule interstitial pathological damage (Experimental I group) and 27 children had renal tubule interstitial pathological damage (Experimental II group). Expression of TGF-beta and HGF in kidney tissues was ascertained by the immunohistochemical method.</p><p><b>RESULTS</b>TGF-beta and HGF were expressed in the three groups, but there were significant differences among the three groups. The expression of TGF-beta and HGF in the two experiment groups increased significantly compared with that in the control group. The Experimental II group had increased TGF-beta expression but a significantly decreased HGF expression compared with the Experimental I group. The index of tubule interstitial pathological changes was positively correlated with the TGF-beta expression (r=0.763, P<0.01), but negatively correlated with the HGF expression (r=-0.461, P<0.05) in the Experimental II group. There was a negative correlation between TGF-beta and HGF expression in children with primary FSGS (r=-0.425, P<0.05).</p><p><b>CONCLUSIONS</b>The expression of TGF-beta and HGF in kidney tissues is increased in children with primary FSGS. TGF-beta might be a fibrogenic factor and HGF might be an anti-fibrotic factor in the kidney in primary FSGS.</p>
Subject(s)
Child , Humans , Glomerulosclerosis, Focal Segmental , Metabolism , Pathology , Hepatocyte Growth Factor , Immunohistochemistry , Kidney , Chemistry , Kidney Tubules , Pathology , Transforming Growth Factor betaABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of mycophenolate mofetil (MMF) plus prednisone on refractory nephrotic syndrome (RNS) in children.</p><p><b>METHODS</b>One hundred and forty-two children with RNS from ten clinical trial centers were divided into two groups: MMF (n=87) and control (n=55). The MMF group patients were administered with oral MMF (30-40 mg/kg daily) for at least 6 months. Afterwards the patients who responded to MMF received another 6 months MMF treatment at a dosage of 10-20 mg/kg daily. The controls were treated with pulse intravenous infusion of cyclophosphamide (CTX) (10 mg/kg daily) for 2 days every 2 weeks for 3 months. Then CTX was administered at a dosage of 500 mg/m2 once a month 4, 7 and 10 months after treatment. While the patients received MMF or CTX treatment, they were treated with oral prednisone (0.5-1 mg/kg daily) for 2 to 3 months, and then the dosage of prednisone was gradually reduced. Urinary protein, liver and renal functions, and side effects of drugs were examined at regular intervals for one year.</p><p><b>RESULTS</b>Of the 87 patients, 58 achieved complete remission, 16 achieved partial remission, 9 achieved early remission and 4 had no response to treatment. In the control group, 35 achieved complete remission, 9 achieved partial remission, 1 achieved early remission and 10 had no response to treatment. The total remission rate in the MMF group (95.4%) was significantly higher than that in the control group (81.8%) (P<0.01). After treatment 67 patients (65.4%) in the MMF group had negative proteinuria compared with 36 patients (65.4%) in the control group (P>0.05). MMF was found to be more effective in reducing proteinuria, and improving hypoproteinemia, oliguria, hyperlipemia, and edema than CTX. MMF was better tolerated with lower incidences of adverse reactions than CTX.</p><p><b>CONCLUSIONS</b>The combined therapy of MMF and prednisone is more effective and tolerable than pulse intravenous infusion of CTX for treatment of RNS in children.</p>
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Immunosuppressive Agents , Therapeutic Uses , Mycophenolic Acid , Therapeutic Uses , Nephrotic Syndrome , Drug Therapy , Prednisone , Therapeutic Uses , Prospective StudiesABSTRACT
Objective To explore the relationship between clinical and pathological changes of complement 1q(C1q) nephropathy. Methods Clinical manifestation, pathologic features including glomerulus change, renal tubule - interstitial change and im-munopathology were compared between 10 cases of C1q nephropathy in children, who were diagnosed by renal biopsy. Results Presentation included idiopathic nephritic syndrome(6 cases), simple hematuria(2 cases), nephritic syndrome(1 case), rapidly progressive glomerulonephritis( 1 case); Renal biopsy revealed focal segmental glomerulosclerosis( FSGS) in 5, minimal-change disease( MCD) and mesangial proliferative glomerulonephritis (MsPGN) respectively in two and crescentic glomerulonephritis in one. In addition, there were renal - tubule interstitial changes with 3 cases of grade I and grade II each other, 2 of grade III , 1 of grade IV . The prominent immunofluorescent features was the presence of bright mesangial deposition of C1q. The average follow - up time was 25.7 months. Six cases presenting nephrotic syndrome were resistant to steroid, but 5 were released after immunosuppressive therapy, the other had progressive renal insufficiency. Conclusions C1q nephropathy falls with the clinical - pathologic spectrum of FSGS generally. It is also presented as steroid - resistant nephritic syndrome. Moreover, the prognosis of C1q nephropathy is related to renal tubulointerstitial pathologic lesions not to C1q deposition.
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Objective To understand the clinical and pathological features of hepatitis B virus-associated glomerulonephritis(HBV-GN).Methods Twenty children with HBV-GN were analysed including 17 cases of nephritic syndrome (4 cases of simple nephrosis, 13 cases of nephritic nephrosis),2 cases of isolated proteinuria, 1 case of nephritic syndrome according to the clinical classification.Results On the basis of pathology of kidney biopsy, there were 15 cases of membranous glomerulonephritis(MN),3 cases of manbranoproliferative glomerulonephritis(MPGN),2 cases of mesangial proliferative glomerulonephritis(MsPGN).Eight of 20 cases were treated with recombinated human alpha-interfeon. The average follow-up time was 5.7 years. As the result, complete remission clinically was on 5 cases,partial remission on 2 cases and ineffectiveness on one case. Besides, serum HBsAg, HBeAg were converted to negative on 3 cases , HBeAg disappeared and anti-HBe appeared on one case.Conclusion MN is common in childhood with HBV-GN.It also indicates the prognosis of the associated nephropathies is quite favorable.