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1.
Braz. j. med. biol. res ; 55: e11861, 2022. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1364557

ABSTRACT

Nephrotic syndrome is the most common clinical presentation of glomerular disease in elderly patients, and renal biopsy is an important diagnostic resource. The aim of this study was to describe nephrotic syndrome among elderly patients in Brazil, focusing on tubulointerstitial and vascular involvement. This was a retrospective study of patients over 65 years of age with nephrotic syndrome who underwent renal biopsy between January 2012 and December 2019. Of the 123 renal biopsies that occurred during the study period, 44 (35.8%) were performed for the investigation of nephrotic syndrome. Among those 44 cases, the main etiologies were membranous nephropathy in 13 cases (29.5%), amyloidosis in ten (22.7%), non-collapsing focal segmental glomerulosclerosis (FSGS) in four (9.1%), and collapsing FSGS in four (9.1%). Patients with minimal change disease (MCD) had the lowest degree of interstitial fibrosis compared with the other glomerulopathies, and histological signs of acute tubular necrosis (ATN) were less common among those with amyloidosis than among those with membranous nephropathy, FSGS, or MCD (P=0.0077). Of the patients with ATN, the frequency of acute kidney injury (AKI) was highest in those with MCD (P<0.001). All patients had some degree of vascular involvement, regardless of the type of glomerulopathy. In conclusion, the second most common cause of nephrotic syndrome in this population was amyloidosis, and acute interstitial tubule involvement was more marked in MCD. Vascular involvement is something that cannot be dissociated from the age of the patient and is not only due to the underlying glomerulopathy.

2.
Article in Chinese | WPRIM | ID: wpr-908024

ABSTRACT

Objective:To analyse the clinical and prognosis of C1q deposition in children with primary membranous nephropathy (PMN).Methods:A retrospective analysis was conducted in 177 children with PMN who were diagnosed by renal biopsy in the Eastern Theater Cornmand General Hospital from July 2005 to September 2013.Patients were divided into C1q deposit group and C1q non-deposit group according to the immunofluorescence staining of C1q.Clinical and pathological characteristics, treatment response, and long-term renal prognosis were compared between the 2 groups.Results:A total of 177 pediatric patients with PMN were included, involving 98 boys and 79 girls with a median age of 192.0 months.During an follow-up of (52.4±35.6) months, 7 cases(4.0%) progressed end-stage renal disease (ESRD), and 14 cases(7.9%) developed ESRD or renal dysfunction.The blood IgG level of C1q deposit group was higher than that of C1q non-deposit group [(5.10±2.51) g/L vs.(4.34±2.10) g/L, t=2.110, P=0.036]. The frequency of glomerular C4 deposits in C1q deposit group was significantly higher than that of C1q non-deposit group (34.7% vs.2.9%, χ2=32.567, P<0.001). The Kaplan-Meier survival analysis showed that there were no differences in cumulative renal survival rate of ESRD ( P=0.561) and cumulative incidence rate of remission ( P=0.291) between groups.The Logistic regression analysis demonstrated that C1q deposition was not correlated with treatment responses ( P=0.587). Univariate COX regression analysis demonstrated that the male gender ( HR=8.578, 95% CI: 1.120-65.689, P=0.039) and no remission ( HR=0.053, 95% CI: 0.017-0.171, P<0.001) were risk factors for renal dysfunction in children with PMN.Multivariate COX regression analysis reveled that no remission ( HR=21.858, 95% CI: 5.595-85.387, P<0.001) and C1q deposition ( HR=0.116, 95% CI: 0.023-0.584, P=0.009) were independent risk factors for renal dysfunction in children with PMN. Conclusions:C1q deposition was an independent risk factor for renal dysfunction in children with PMN.The classical pathway does occur in some PMN patients, which plays an essential role in mediating kidney injury.

3.
Article in Chinese | WPRIM | ID: wpr-906515

ABSTRACT

Objective:To observe the effect of modified Shengjiangsan on renal fibrosis in rats with membranous nephropathy (MN) and to explore the mechanism of its complications of renal fibrosis. Method:Rats were injected with cationized bovine serum albumin(C-BSA)in the tail vein to establish a rat model of membranous nephropathy. The normal group,model group,modified Shengjiangsan group (27.3 g·kg<sup>-1</sup>)and benazepril group(10 mg·kg<sup>-1</sup>)were established in this study. Each group was given corresponding dosage of the drug once a day for 4 weeks of continuous intervention. After the administration,we observed the pathological changes of rat kidneys by the technology of Masson staining, silverhexylamine iodate (PASM) staining, transmission electron microscopy (TEM), immunofluorescence technology (IF) was used to detect immunoglobulin(Ig)G deposition in rat kidneys. The levels of interleukin-1<italic>β</italic> (IL-1<italic>β</italic>), interleukin-6 (IL-6), tumor necrosis factor-<italic>α</italic> (TNF-<italic>α</italic>) in rat serum were detected by enzyme-linked immunosorbent assay (ELISA) method. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and immunohistochemistry (IHC) were used to detect the mRNA and protein expression levels of monocyte chemotactic protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), nuclear factor kappa B (NF-<italic>κ</italic>B), Toll-like receptor 4 (TLR4), plasminogen activator inhibitor 1 (PAI-1), transforming growth factor-<italic>β</italic><sub>1</sub> (TGF-<italic>β</italic><sub>1</sub>), <italic>α</italic>-smooth muscle actin (<italic>α</italic>-SMΑ) and type Ⅳ Collagen (Collagen Ⅳ) in rat kidney tissues. Result:Compared with normal group, the kidney tissue of the model group was obviously fibrotic, the serum levels of IL-1<italic>β</italic>, IL-6, and TNF-<italic>α</italic> were significantly increased(<italic>P</italic><0.05), and the expressions of MCP-1, ICAM-1, NF-<italic>κ</italic>B, TLR4, PAI-1, TGF-<italic>β</italic><sub>1</sub>, <italic>α</italic>-SMA and Collagen Ⅳ mRNA and protein in kidney tissue were significantly increased(<italic>P</italic><0.05). Compared with model group, modified Shengjiangsan and benazepril significantly improved renal fibrosis in rats, reduced the levels of IL-1<italic>β</italic>, IL-6, and TNF-<italic>α</italic> in the serum of MN rats(<italic>P</italic><0.05), down-regulated MCP-1, ICAM-1, NF-<italic>κ</italic>B, TLR4, PAI-1, TGF-<italic>β</italic><sub>1</sub>, <italic>α</italic>-SMA and Collagen Ⅳ mRNA and protein expression in kidney tissue(<italic>P</italic><0.05). Conclusion:Modified Shengjiangsan can reduce the release and expression of inflammatory factors by down-regulating the TLR4/NF-<italic>κ</italic>B signaling pathway, inhibit renal fibrosis, and reduce renal damage in MN rats.

4.
Article in Chinese | WPRIM | ID: wpr-906393

ABSTRACT

Objective:To observe the effects of Yishen Tongluo prescription (YTP) on autophagy-related proteins in rats with membranous nephropathy (MN) and explore its possible molecular mechanism in protecting the kidney. Method:Twenty of 80 Sprague-Dawley (SD) rats were randomly selected as the normal control, and the rest rats were pre-immunized and injected with cationized bovine serum albumin (C-BSA) through the tail vein to induce MN. The SD rats that were successfully modeled were randomized into the model group, benazepril hydrochloride group (10 mg·kg<sup>-1</sup>), and low- (6.61g·kg<sup>-1</sup>), medium- (13.22 g·kg<sup>-1</sup>), and high-dose (26.44 g·kg<sup>-1</sup>) YTP groups, and administered with the corresponding drugs by gavage, once a day, for four consecutive weeks. Then the changes in such quantitative indicators as plasma albumin (ALB), triglyceride (TG), total cholesterol (TC), serum creatinine (SCr), blood urea nitrogen (BUN), and 24-hour urinary total protein (UTP) were detected, followed by hematoxylin and eosin (HE) staining, Masson's trichrome staining, and periodic Schiff-methenamine (PASM) staining for observing the pathological changes in kidney under the transmission electron microscope (TEM). The deposition of immunoglobulin G (IgG) and complement 3 (C3) in the glomerulus was detected by fluorescence immunoassay. The expression levels of autophagy marker proteins Beclin-1, microtubule-associated protein light chain 3Ⅱ (LC3Ⅱ), and p62 were measured by immunohistochemistry (IHC), and those of related proteins in the adenosine monophosphate-activated protein kinase / mechanisic target of rapamycin/Unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway were determined by Western blot assy. Result:Compared with the normal group, the model group exhibited significantly increased UTP (<italic>P</italic><0.01) and serum TG and TC (<italic>P</italic><0.01), decreased ALB (<italic>P</italic><0.01), disordered glomerular structure, enlarged volume, thickened basement membrane, vacuolated renal tubules, excessively deposited collagen fibers and fuchsinophilic proteins, extensively fused podocyte foot processes, and diffusely deposited IgG and C3 in glomerular capillary loops. Besides, the expression levels of Beclin-1, LC3II, and phosphorylated AMPK (p-AMPK) decreased (<italic>P</italic><0.01), while those of p62, phosphorylated mTOR (p-mTOR), and phosphorylated ULK1 (p-ULK1) increased (<italic>P</italic><0.01). The comparison with the model group revealed that the TG, TC, and UTP levels in the low-, medium-, and high-dose YTP groups and the benazepril hydrochloride group were reduced to varying degrees (<italic>P</italic><0.05, <italic>P</italic><0.01), whereas the ALB level was increased (<italic>P</italic><0.01). There was no statistically significant difference in SCr or BUN level. The pathological damages were alleviated. The expression levels of Beclin-1, LC3Ⅱ, and p-AMPK were up-regulated (<italic>P</italic><0.05, <italic>P</italic><0.01), while those of p62, p-mTOR, and p-ULK1 were down-regulated (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:YTP protects the kidney of rats with MN possibly by regulating related proteins in the AMPK/mTOR/ULK1 signaling pathway and activating the autophagy.

5.
Article in Chinese | WPRIM | ID: wpr-906175

ABSTRACT

Objective:To study the effect of Fuzheng Qufeng prescription (FZQP) on transforming growth factor-<italic>β</italic><sub>1</sub> (TGF-<italic>β</italic><sub>1</sub>)/Smad signaling pathway and epithelial-mesenchymal transition of podocyte in membranous nephropathy (MN) rats and to explore its molecular mechanism for podocyte protection. Method:The rats were randomly divided into normal control group (NC) and modeling group. Rats in modeling group induced by bovine serum albumin (C-BSA) were randomly divided into model group (MN), losartan potassium group (LP, 0.05g·kg<sup>-1</sup>), and FZQP high dose (FZQPH, 41 g·kg<sup>-1</sup>), medium dose (FZQPM, 20.5 g·kg<sup>-1</sup>), and low dose (FZQPL, 10.25 g·kg<sup>-1</sup>) groups. The administration lasted for 4 weeks. In week 0, 2, and 4 of administration, the levels of 24 hours urine protein (24 h-Upro) were tested. At the end of 4th week, the levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected, and the rats in each group were sacrificed and the renal pathological morphology changes were observed by light microscope with hematoxylin-eosin (HE), Masson and periodic acid-silver metheramine (PASM) staining. The deposition of immune complex, the thickening of glomerular basement membrane (GBM) and podocyte foot process were observed by transmission electron microscope (TEM). The distribution and expression intensity of Desmin in renal tissues were detected by immunohistochemistry (IHC). The mRNA and protein expression levels of TGF-<italic>β</italic><sub>1</sub>, Smad2/3, phospho(p)-Smad2/3, Smad7 and Desmin in renal tissues were respectively detected by Western blot (WB) and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result:Compared with NC group, the levels of 24 h-Upro, BUN and SCr significantly increased in model group (<italic>P</italic><0.01), with increased deposition of immune complex, significantly thickened GBM and fusion of foot processes, significantly increased Desmin mRNA and protein expression (<italic>P</italic><0.01) and increased TGF-<italic>β</italic><sub>1</sub>, Smad2, and Smad3 mRNA and protein expression (<italic>P</italic><0.05), and decreased Smad7 mRNA and protein expression (<italic>P</italic><0.05,<italic>P</italic><0.01). Compared with model group, 24 h-Upro and BUN decreased in FZQP groups and LP group (<italic>P</italic><0.05), levels of serum SCr in FZQPM group decreased (<italic>P</italic><0.05), deposition of immune complex, thickening of GBM and fusion of foot process were all alleviated in FZQP groups and LP group. Distribution of Desmin along GBM decreased in FZQPH group, FZQPM group and LP group (<italic>P</italic><0.05). Both mRNA and protein expression levels of TGF-<italic>β</italic><sub>1</sub> and p-Smad2/Smad2 in FZQPM group decreased, while mRNA and protein expression levels of Smad7 increased (<italic>P</italic><0.05). Both mRNA and protein expression levels of p-Smad3/Smad3 in FZQPH group decreased (<italic>P</italic><0.05). Both mRNA and protein expression levels of Desmin in podocyte in FZQPH group, FZQPM group and LP group decreased (<italic>P</italic><0.05). Conclusion:FZQP might realize podocyte protection effect in MN via suppressing EMT mediated by overactivated TGF-<italic>β</italic><sub>1</sub>/Smad signaling pathway.

6.
Article in Chinese | WPRIM | ID: wpr-906160

ABSTRACT

Traditional Chinese medicine (TCM) is a great treasure house, exhibiting unique advantages in the treatment of some difficult and critical diseases. The incidence rate of membranous nephropathy has increased year by year in recent years, and has become the first cause of primary glomerular diseases. However, its pathogenesis is not clear. Modern medicine often uses immunosuppressive therapy, but it often faces the problems of high side effects and high recurrence rate. The China Association of Chinese Medicine (CACM) invited clinical experts of TCM and western medicine to fully discuss membranous nephropathy, which was later confirmed to be one of the clinical diseases responding specifically to TCM. Apart from summarizing the pathogenesis and clinical diagnosis and treatment of membranous nephropathy in both TCM and western medicine, this paper also detailed TCM cognition, syndrome differentiation, and therapeutic schemes of membranous nephropathy, aiming to improve the clinical remission rate of membranous nephropathy and provide reference for its clinical treatment.

7.
Article in Chinese | WPRIM | ID: wpr-906051

ABSTRACT

Objective:To investigate the intervention effect of modified Shengjiangsan on hypoxia-inducible factor-1<italic>α </italic>(HIF-1<italic>α</italic>)/nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) signaling pathway in membranous nephropathy (MN) rats and to explore its mechanism to reduce oxidative stress and apoptosis in renal tissues. Method:Cationized bovine serum albumin (C-BSA) was injected into the tail vein of rats to replicate the MN model. Rats were randomly divided into a model group, a modified Shengjiangsan group, and a benazepril group after modeling, and administered by gavage once a day accordingly. At the end of the 4<sup>th</sup> week, the 24-h urine total protein (UTP), urea nitrogen (BUN), and serum creatinine (SCr) levels of each group were detected. Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) in renal tissues of rats. In situ end labeling(TUNEL) staining was used to detect the cell apoptosis rate. The mRNA and protein expression levels of HIF-1<italic>α</italic> and NOX4 were detected by real-time fluorescence-based quantitative polymerase chain reaction(Real-time PCR)and Western blot, respectively. The immunohistochemistry method was used to detect the protein expression levels of B-cell lymphomas -2 (Bcl-2), B-cell lymphomas xl (Bcl-xl), Bcl-2 associated X protein (Bax), Bcl-2 cell death regulator antibody (Bim). Result:Compared with the normal group, the model group showed increased UTP (<italic>P</italic><0.05), decreased SOD, elevated MDA and ROS (<italic>P</italic><0.05), up-regulated mRNA and protein expression of HIF-1<italic>α</italic> and NOX4 (<italic>P</italic><0.05), enhanced protein expression of Bax and Bim, declining protein expression of Bcl-xl and Bcl-2 (<italic>P</italic><0.05), and increased cell apoptosis in renal tissues. Compared with the model group, the modified Shengjiangsan group and the benazepril group displayed declining UTP (<italic>P</italic><0.05), up-regulated SOD, decreased MDA and ROS (<italic>P</italic><0.05), down-regulated mRNA and protein expression of HIF-1<italic>α</italic> and NOX4 (<italic>P</italic><0.05), diminished protein expression of Bax and Bim, elevated protein expression of Bcl-xl and Bcl-2 (<italic>P</italic><0.05), and reduced cell apoptosis in renal tissues (<italic>P</italic><0.05). Conclusion:The protective effect of modified Shengjiangsan on the kidney is presumedly achieved by reducing the oxidative stress and apoptosis in renal tissues of MN rats via inhibiting the HIF-1<italic>α</italic>/NOX4 signaling pathway.

8.
Article in Chinese | WPRIM | ID: wpr-906019

ABSTRACT

Objective:To investigate the renoprotective effects that Sanjiao Qushi prescription ameliorates cationic bovine serum albumin (C-BSA) induced membranous nephropathy(MN) in mice model and its influence on nuclear factor erythroid-2-related factor-2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway. Method:Sixty female BALB/c mice were randomly divided into the normal group(<italic>n</italic>=10) and the model group(<italic>n</italic>=50). The mice in the model group received C-BSA injection via tail vein (6.5 mg·kg<sup>-1</sup>). The mice that were successfully modeled were randomized into the model group, the low dose Sanjiao Qushi prescription group(3.71 g·kg<sup>-1</sup>), the high dose Sanjiao Qushi prescription group(7.42 g·kg<sup>-1</sup>) and benazepril hydrochloride group(1.3 mg·kg<sup>-1</sup>). And they were administered with the corresponding medicine by gavage once a day for four consecutive weeks. 24 hour-urine protein quantitation were performed before C-BSA injection and after C-BSA injection as well as the medicine gavage. When the treatment was finished, all of the mice were sacrificed and the biochemical indicators such as serum creatinine(SCr), blood urea nitrogen(BUN), triglyceride(TG), total cholesterol(TC), total protein(TP) and albumin(Alb) were measured. And the renal pathological morphology changes were observed by light microscope with hematoxylineosin(HE), Masson and periodic acid-silver metheramine(PASM) staining. The deposition of immunoglobulin G(IgG) in the glomerulus was detected by fluorescence microscope. The expression of reactive oxygen species (ROS) of kidney was detected by fluorescence immunoassay. The protein expression levels of Nrf2 in cell nucleus and cytoplasm and the downstream protein factors HO-1 and NADH quinone acceptor oxidoreductase 1(NQO1) were detected by Western blot. Result:Compare to normal group, the levels of 24 hour-urine protein quantitation, TG and TC significantly increased in model group(<italic>P</italic><0.01), while TP and Alb levels significantly decreased(<italic>P</italic><0.01). The model group exhibited enlarged volume of glomerular, significantly thickened glomerular basement membrane(GBM), fuchsinophilic protein deposition and spike formation through light microscope. Immunofluorescence staining for the model group exhibited granular deposition of IgG along the capillary wall. The expression of ROS in kidney significantly increased(<italic>P</italic><0.01). The protein expression levels of Nrf2 in cell nucleus significantly increased(<italic>P</italic><0.01), while Nrf2 in cytoplasm significantly decreased(<italic>P</italic><0.01).The protein expression levels of HO-1 and NQO1 significantly increased(<italic>P</italic><0.01). Compared to model group, the levels of 24 hour-urine protein quantitation, TG and TC significantly decreased in each treated group(<italic>P</italic><0.01), TP and Alb levels significantly increased(<italic>P</italic><0.05,<italic>P</italic><0.01). The pathological damages alleviated obviously. The expression of ROS in kidney significantly decreased(<italic>P</italic><0.01). The protein expression levels of Nrf2 in cell nucleus significantly decreased(<italic>P</italic><0.01), while Nrf2 in cytoplasm significantly increased(<italic>P</italic><0.05,<italic>P</italic><0.01). The protein expression levels of HO-1 and NQO1 significantly increased(<italic>P</italic><0.01). Conclusion:Sanjiao Qushi prescription worked on MN mice possibly by regulating related proteins in the Nrf2/HO-1 signaling pathway and relieving oxidative stress, thus decreasing 24 hour-urine protein and blood lipid, increasing serum protein, and alleviating the pathological damages to protect renal function and delay progress of the disease.

9.
Article in Chinese | WPRIM | ID: wpr-905931

ABSTRACT

Objective:To study the protective effect of polysaccharides from Plantaginis Semen (PSP) against renal injury in rats with membranous nephropathy (MN) and its influence on the gut microbiota to provide a theoretical basis for the further investigation of PSP in the treatment of MN. Method:The MN model was induced by tail vein injection of cationic bovine serum albumin (C-BSA, 3.5 g·L<sup>-1</sup>) in rats with a modeling period of seven weeks. At the 4th week of modeling, the model rats were divided into a model group, a positive drug group (benazepril hydrochloride, 10 mg·kg<sup>-1</sup>·d<sup>-1</sup>), a PSP high-dose group (PSP-H, 800 mg·kg<sup>-1</sup>·d<sup>-1</sup>), a PSP medium-dose group (PSP-M, 400 mg·kg<sup>-1</sup>·d<sup>-1</sup>), and a PSP low-dose group (PSP-L, 200 mg·kg<sup>-1</sup>·d<sup>-1</sup>) according to the random number table, with 10 in each group. Ten healthy rats were assigned to the normal control group. The rats in the normal control group and the control group received an equal amount of physiological saline by gavage, and those in the groups with drug intervention were administered correspondingly,once a day,for consecutive four weeks. The pathological changes of rat kidney and colon tissues were observed by optical microscopy. The enzyme-linked immunosorbent assay (ELISA) was used to detect the content of tumor necrosis factor-<italic>α </italic>(TNF-<italic>α</italic>) and interleukin-1<italic>β </italic>(IL-1<italic>β</italic>) in the serum and colon tissues. The immunohistochemistry (IHC) was used to detect the protein expression of TNF-<italic>α </italic>and IL-1<italic>β </italic>in renal tissues. The 16S rRNA sequencing method was used to investigate the effect of PSP on the gut microbiota in MN rats. Result:Compared with the normal control group, the model group showed enlarged glomeruli, thickened basement membrane, atrophied colonic gland, increased TNF-<italic>α</italic> and IL-1<italic>β</italic> in the serum and colon tissues (<italic>P</italic><0.05), and elevated protein expression of TNF-<italic>α</italic> and IL-1<italic>β </italic>(<italic>P</italic><0.01). Compared with the model group, the positive drug group and the PSP-H group displayed shrunk glomerular capsules, relieved basement membrane thickening, and neatly arranged colonic mucosa in colon tissues, while the PSP-M and PSP-L groups were inferior in improving renal tissues and colon tissues. Additionally, the PSP-H and PSP-M groups showed declining TNF-<italic>α</italic> and IL-1<italic>β</italic> in the serum and colon tissues (<italic>P</italic><0.05) and dwindled protein expression of TNF-<italic>α</italic> and IL-1<italic>β </italic>in the renal tissues (<italic>P</italic><0.01). No significant difference was observed in the PSP-L group. Compared with the normal control group, the model group showed increased abundance of Firmicutes and decreased abundance of Bacteroidetes. After PSP intervention, the abundance of Firmicutes was decreased, while that of Bacteroidetes was increased, and such changes were predominant in the PSP-H group. Conclusion:PSP can effectively alleviate renal injury, reduce the expression of inflammatory factors, regulate the structure of gut microbiota, and improve the damaged intestinal barrier of MN rats.

10.
Article in Chinese | WPRIM | ID: wpr-905829

ABSTRACT

Objective:The purpose of this article was to observe the effect of modified Shengjiangsan on podocyte apoptosis in membranous nephropathy (MN) rats, to explore the molecular mechanism of its treatment of MN and to provide experimental basis for its clinical application. Method:The MN rat model was established by injection of cationic bovine serum albumin into the tail vein of rats. The successfully modeled rats were then randomly divided into model group (equal volume of normal saline), modified Shengjiangsan group (27.3 g·kg<sup>-1</sup>) and benazepril group (10 mg·kg<sup>-1</sup>), with corresponding drug dosage once a day for 4 weeks of continuous intervention. After drug administration, the 24-hour urine protein (UTP) was detected. Real time fluorescent quantitative polymerase chain reaction (Real-time PCR) and immunohistochemical (IHC) methods were used to detect Podocalyxin, Nephrin, Podocin, Synaptopodin mRNA and protein expression levels in rat kidney tissue. terninal-deoxynucleoitidyl transferase medsated nick and labeling (TUNEL) method was used to detect cell apoptosis rate in rat kidney tissue, and Western blot was used to detect Notch1, Hes1, B lymphoblastoma-2 (Bcl-2) associated X protein (Bax), and Bcl-2 protein expression levels in rat kidney tissue. Result:Compared with the normal group, UTP in the model group increased significantly, renal tissue cell apoptosis increased significantly, podocyte marker proteins podocalyxin, Nephrin, Podocin, Synaptopodin mRNA and protein expression levels decreased significantly, and Notch1, Hes1, Bax protein expression increased significantly, and Bcl-2 protein expression was significantly reduced(<italic>P</italic><0.05). Compared with the model group, UTP levels in MN rats were significantly reduced in modified Shengjiangsan and benazepril groups, with reduced rate of renal cell apoptosis, increased mRNA and protein expression levels of podocalyxin, Nephrin, Podocin, and Synaptopodin in renal tissue, decreased Notch1, Hes1, Bax protein expression, and increased Bcl-2 protein expression(<italic>P</italic><0.05). Conclusion:Modified Shengjiangsan can inhibit the Notch signaling pathway, reduce the apoptosis of rat kidney tissue podocytes, and reduce the kidney injury of MN rats.

11.
Chinese Acupuncture & Moxibustion ; (12): 1216-1220, 2021.
Article in Chinese | WPRIM | ID: wpr-921035

ABSTRACT

OBJECTIVE@#To compare the effect of moxibustion combined with basic treatment and simple basic treatment on the clinical symptoms, renal function and hypercoagulable state in patients with idiopathic membranous nephropathy (IMN) of low to medium risk with spleen-kidney deficiency and blood stasis.@*METHODS@#A total of 60 patients with IMN of low to medium risk with spleen-kidney deficiency and blood stasis were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 1 case dropped off). In the control group, the conventional basic treatment of anti-hypertension, regulating blood lipid and anti-coagulation was adopted. On the basis of the control group, moxibustion was applied at Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, once a day, 5 days a week continuously with 2 day interval. The treatment of 6 months was required in the both groups. Before treatment and 3 and 6 months into treatment, the total TCM syndrome score, the renal function indexes (24-hour urinary protein quantity [UTP], albumin [ALB], urea nitrogen [BUN] and creatinine [Scr]), the blood coagulation indexes (fibrinogen [FIB], D-Dimer [D-D], p-selection and von Willebrand factor [vWF]), total cholesterol (TC) and triacylglycerol (TG) levels were observed, and the therapeutic efficacy was evaluated on 3 and 6 months into treatment in the two groups.@*RESULTS@#The effective rates of 3 and 6 months into treatment were 78.6% (22/28) and 89.3% (25/28) in the observation group, which were higher than 62.1% (18/29) and 75.9% (22/29) in the control group respectively (@*CONCLUSION@#Moxibustion combined with basic treatment can effectively improve the clinical symptoms, renal function and renal microcirculation in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis, the therapeutic effect is superior to the simple basic treatment.


Subject(s)
Acupuncture Points , Acupuncture Therapy , Glomerulonephritis, Membranous , Humans , Kidney/physiology , Moxibustion , Spleen
12.
Article in Chinese | WPRIM | ID: wpr-911764

ABSTRACT

Objective:To analyze characteristics and trends of histopathological diagnosis of adult renal biopsy in Beijing from 2008 to 2020.Methods:A total of 4 652 cases of adult renal biopsy were collected from three hospitals in Beijing between 2008 and 2020. The patients were divided into three age groups: 18-40 years, 40-65 years and≥ 65 years; and also divided into three period: 2008-2011, 2012-2015, and 2016-2020. The pathological characteristics and changes of renal biopsy were analyzed in three age groups at different periods.Results:Among 4 652 cases primary glomerular disease accounted for 81.8%, the membranous nephropathy (MN, 32.4%, 1 509/4 652), IgA nephropathy (IgAN, 29.2%, 1 356/4 652) and minor glomerular abnormalities (MGA, 11.3%, 526/4 652) were the top three pathological types. The overall proportion of MN and diabetic nephropathy (DN) increased from 20.3% and 2.3% in 2008-2011 to 37.3% and 10.1% in 2016-2020) (χ2=99.9 and 96.1, both P<0.01), respectively. For age group 18-40 years, the MN and DN increased from 11.2% and 1.6% in 2008-2011 to 24.7% and 5.5% in 2016-2020 (χ2=32.7 and 20.7, both P<0.01), respectively. For age group 40-65 years the MN and DN increased from 26.6% and 3.2% in 2008-2011 to 41.5% and 13.1% in 2016-2020 (χ2=39.1 and 57.3, both P<0.01), respectively. For age group≥65 years the MN was the most common pathological type in the three periods, fluctuating between 41.3% and 55.0% (χ2=5.2, P=0.08); and DN increased from 0(0/63) in 2008-2011 to 7.5%(22/292) in 2016-2020 (χ2=8.1, P=0.02). Conclusion:The renal biopsy data show that membranous nephropathy and diabetic nephropathy are the most common primary and secondary adult glomerular diseases in Beijing recently.

13.
Article in Chinese | WPRIM | ID: wpr-872820

ABSTRACT

Objective:To explore the intervention effect of modified Shengjiangsan in rats with membranous nephropathy (MN) and its related mechanism. Method:Rats were injected with cationized bovine serum Albumin (C-BSA) in the tail vein to establish a rat model of membranous nephropathy. The normal group, model group, modified Shengjiangsan group (27.3 g·kg-1) and benazepril group (10 mg·kg-1) were established in this study. Each group was given corresponding dosage of the drug once a day for 4 weeks of continuous intervention. After the administration, the levels of 24-hour urine protein (UTP), total cholesterol (TC), triglyceride (TG), total protein (TP), Albumin (Alb), creatinine (SCr), urea nitrogen (BUN) level was detected. we observed the pathological changes of rat kidneys by the technology of Masson staining, silver hexylamine iodate (PASM) staining and transmission electron microscopy. immunofluorescence technology was used to detect immunoglobulin (Ig)G deposition in rat kidneys. Western blot was used to detect the expression levels of key proteins in phosphatidylinositol 3-kinase/proline protein kinase B/rapamycin target protein (PI3K/Akt/mTOR) signaling pathway and autophagy marker proteins LC3 and Beclin1. Result:Compared with normal group, the UTP, serum TC and TG levels were significantly increased, TP and Alb levels were significantly reduced in model group(P<0.05). We detected the kidney pathological changes include of glomerulus enlargement, basement membrane thickening,vacuolar degeneration, pheotropin deposition, glomerular capillary loop IgG diffuse deposition, electron dense deposits of varying sizes and podocytes under the epithelium extensive integration of foot processes, the expression of p-PI3K, p-Akt and p-mTOR protein was significantly increased (P<0.05). The expression of autophagy marker proteins LC3 and Beclin1 protein decreased significantly(P<0.05). Compared with model group, the UTP, serum TC and TG levels were decreased in the benazepril group and modified Shengjiangsan group, and the TP and Alb levels were increased (P<0.05), the histopathological changes of rat kidney were all reduced, the expression of p-PI3K, p-Akt and p-mTOR protein was significantly reduced(P<0.05), autophagy marker proteins LC3 and Beclin1 protein expression were significantly increased. Conclusion:Modified Shengjiangsan can reduce urinary protein, reduce kidney pathological damage and delay disease progression, which is related to its inhibition of PI3K/Akt/mTOR signaling pathway and activation of renal autophagy.

14.
Article in English | WPRIM | ID: wpr-827366

ABSTRACT

OBJECTIVES@#To evaluate the value of thrombospond in Type I domain-containing 7A (THSD7A) and M-type phospholipase A2 receptor (PLA2R) in primary membranous nephropathy (PMN) and to explore the relationship between their antibody levels and prognosis.@*METHODS@#Renal tissues in 128 patients with membranous nephropathy in the Second Xiangya Hospital of Central South University were collected from February 2015 to August 2017, including 108 patients with primary membranous nephropathy (PMN group) and 20 patients with secondary membranous nephropathy (SMN) (SMN group). Indirect immunofluorescence method was used to detect the expression of PLA2R antigen in kidney tissues,and the glomerular expression of THSD7A antigen was examined by immunohistochemistry and indirect immunofluorescence. The serum levels of anti-PLA2R antibodies and THSD7A antibodies were also detected by ELISA. According to the results of PMN examination,the patients were also divided into a PLA2R-related membranous nephropathy group and a THSD7A-related membranous nephropathy group.@*RESULTS@#The positive rate of PLA2R in the renal tissues in the PMN group was higher than that in the SMN group (78% in the PMN group, 35% in the SMN group, <0.01),while the positive rate of anti-PLA2R antibody in the PMN group was also higher than that in the SMN group (50% in the PMN group, 25% in the SMN group, <0.05).The serum level of anti-PLA2R antibody was positively correlated with 24 h urine protein (=0.254, <0.05) and negatively correlated with serum albumin (=-0.236, <0.05). The expression of THSD7A was positive in glomeruli in 7 cases of the PMN group (6%) by immuno-histochemistry, and which was positive in 1case of the SMN group (5%).The serum levels of anti-THSD7A antibody in the PMN group were higher than those in the SMN group [(0.49±0.26) pg/mL in the PMN group,(0.34±0.27) pg/mL in the SMN group, <0.05]. There was no difference in the clinical characteristics between the PLA2R-related membranous nephropathy group and the THSD7A-related membranous nephropathy group.@*CONCLUSIONS@#PLA2R and THSD7A are the target antigen of PMN, and the associated autoantibodies are helpful for the differential diagnosis of PMN. The anti-PLA2R antibody levels can reflect the severity of the disease and evaluate the effect of treatment. The incidence of THSD7A membranous nephropathy is low, and monitoring the serum anti-THSD7A antibody levels can assess patients' condition and predict disease outcome.


Subject(s)
Autoantibodies , Glomerulonephritis, Membranous , Humans , Immunohistochemistry , Receptors, Phospholipase A2 , Thrombospondins
15.
China Pharmacy ; (12): 1575-1583, 2020.
Article in Chinese | WPRIM | ID: wpr-822622

ABSTRACT

OBJECTIVE:To investigate the protective effect an d possible m echanism of Shenqi zhilong decoction (SZD) combined with Tripterygium polyglycoside tablets (TPT)on membranous nephropathy (MN)model rats. METHODS :MN rat model was established by subcutaneous and caudal vein injecting cationic bovine serum albumin + incomplete Freund adjuvant emulsion for 6 weeks. At the 3rd week of modeling ,model rats were randomly divided into model control group ,SZD low-dose and high-dose groups (4,8 g/kg,by total crude drugs ),TPT group (9 mg/kg),low-dose and high-dose of SZD+TPT groups (same dose as single group ),with 10 rats in each group according to 24 h UTP and weight. Another 10 rats withoutmodeling were taken as blank control group. Blank control group was given equal amount of water intragastrically administration groups were given relevant medicine intragastrically,once a day ,for consecutive 4 weeks. The 24 h UTP of rats were detected one day before the last administration;1 h after the la st administration ,blood routine 中indexes(WBC,RBC,PLT),liver func tion indexes (TP,ALB,AST,ALT),blood lipid indexes (TC,TG,HDL-C,LDL-C), the contents of glucose (GLU),urea nitrogen (BUN)and serum creatinine (Scr)were detected in each group. Uranyl acetate-lead citrate staining was used to observe ultrastructural changes of renal tissue. Immunohistochemical method was used to detect the protein expression of TGF-β1 and HPA- 1 in renal tissue. RESULTS :Compared with blank control group ,in the model control group,the glomerular podocytes were widely fused or disappeared ,microvilli were formed ,basement membrane was heavily thickened,a large number of electron dense substance was deposited under the epithelium ,TGF-β1 and HPA- 1 positive cells were significantly increased ;24 h UTP ,PLT,the contents of TC ,TG and HDL-C ,the percentage of TGF-β1 and HPA- 1 positive cells were increased significantly ,while RBC ,the contents of TP and ALB were decreased significantly (P<0.05 or P<0.01). Compared with model control group ,above ultrastructural changes of administration groups were improved to different extents ,and TGF-β1 and HPA- 1 positive cells were decreased. The 24 h UTP ,the percentage of TGF-β1 positive cells (except for SZD low-dose group),WBC(except for SZD alone groups and combination groups ),PLT and TC content (except for TPT group ),TG content (except for SZD low-dose alone and its combination group ),the percentage of HPA- 1 positive cells were decreased significantly ; the percentage of TGF-β1 positive cells in SZD high-dose+TPT group as well as the percentage of HPA- 1 positive cells in SZD+TPT groups were significantly lower than TPT group. RBC and GLU content (except for SZD low-dose group and TPT group ),TP and ALB content (except for SZD low-dose group )were increased significantly ,while the content of GLU in SZD high-dose+TPT group was significantly higher than TPT tablets group (P<0.05 or P<0.01). CONCLUSIONS :SZD combined with TPT can relieve myelosuppression caused by TPT ,reduce proteinuria of MN model rats and improve pathological damage of renal tissue in rats. Its mechanism is related to the down-regulation of protein expression of TGF-β1 and HPA- 1,and the reduction of TC and TG content in the blood.

16.
Acta Pharmaceutica Sinica ; (12): 2960-2967, 2020.
Article in Chinese | WPRIM | ID: wpr-862296

ABSTRACT

The goal of this work was to establish a population pharmacokinetics (PPK) model of tacrolimus in idiopathic membranous nephropathy (IMN) patients and to identify potential covariates that influence pharmacokinetic of tacrolimus. A total of 610 data points on the blood concentration of tacrolimus were collected from 96 IMN patients in routine clinical settings. Nonlinear mixed-effect modeling (NONMEM) was used to investigate the effects of CYP3A5 genotype, age, gender, weight, laboratory tests and co-therapy medications on the pharmacokinetic of tacrolimus. The PPK model was evaluated by the goodness-of-fit (GOT), bootstrap and prediction corrected visual predictive check (pc-VPC). The pharmacokinetic of tacrolimus was described by a one-compartment model. The apparent clearance (CL/F) of CYP3A5*1/*3 and *1/*1 were 1.57 and 1.86 times of that of *3/*3, respectively. The CL/F of tacrolimus was 73.6% in patients undergoing co-therapy with Wuzhi capsules, and 1.2 times than that of the patients undergoing co-therapy with Jinshuibao capsules. The evaluation of the model shows that the model is stable and has satisfactory predictive performance. The clinical trial was approved by the Society of Ethics and conducted in Binzhou Medical University Hospital. The established PPK model can describe the pharmacokinetic characteristics of tacrolimus in Chinese patients with IMN, and can facilitate individualized therapy with tacrolimus.

17.
Rev. nefrol. diál. traspl ; 39(4): 266-270, dic. 2019. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1377059

ABSTRACT

Abstract Membranous nephropathy is a glomerular disease that causes nephrotic syndrome. Absent phospholipase A2 receptor antibodies and absent staining with IgG4 may be linked to malignancy-associated MN. Here we present a case that defies that suggestion. A 42-year-old female presented with anasarca. Kidney biopsy revealed membranous nephropathy, stained positive for IgG but negative for IgG4. Absent phospholipase A2 receptor antibodies was negative. Abdominal tomography revealed a partial thrombosis of the left ovarian vein which raised suspicion for ovarian cancer. Even though her ovaries did not uptake FDG on PET scan, a carbohydrate antigen-125 was ordered. She had extremely high levels of carbohydrate antigen-125 which was unexpected in the course of benign events. Thorax CT, endoscopy, colonoscopy, mammography, and positron emission tomography were clear in terms of malignancy. Samples from both pleural effusion and ascites were consistent with transudate. Tuberculosis tests were negative. Cytology samples were negative for malign cells. Exploratory surgery was planned but rejected by the patient. She was treated as primary disease with cyclosporine and methylprednisolone. Rituximab was off-limits due to insurance rules. She had prompt and excellent response. Steroids were tapered and stopped at sixth month and cyclosporine at twelfth month. In her 36 months of drug-free follow up there has been no disease recurrence or a sign of cancer. Even when all odds are towards malignancy-associated membranous nephropathy, primary disease is still a possibility. We need better markers for malignancy-associated membranous nephropathy.A very high level of CA-125 does not necessarily mean cancer.


Resumen La nefropatía membranosa es una enfermedad glomerular que causa el síndrome nefrótico. La ausencia de anticuerpos contra el receptor de fosfolipasa A2 y de tinción para IgG4 puede deberse a una nefropatía membranosa asociada a cáncer. A continuación, se presenta un caso que desafía esta sugerencia. Una paciente de 42 años realizó una consulta por anasarca. A partir de la biopsia de riñón, se diagnosticó nefropatía membranosa con tinción positiva para IgG, pero negativa para IgG4. No se detectó la presencia de anticuerpos contra el receptor de fosfolipasa A2. La tomografía abdominal reveló una trombosis parcial en la vena ovárica izquierda, lo cual generó sospecha de cáncer de ovario. Si bien los ovarios no mostraron absorción de FDG en la tomografía por emisión de positrones, se solicitó una prueba de antígeno carbohidrato 125. Se le detectaron niveles elevados del antígeno carbohidrato 125, lo cual no es esperable en casos de eventos benignos. La tomografía computarizada de tórax, endoscopía, colonoscopía, mamografía y tomografía por emisión de positrones no mostraron tumores. Las muestras de derrame pleural y de ascitis fueron indicativas de trasudado. Las pruebas de tuberculosisarrojaron resultados negativos. El examen citológico fue negativo para células malignas. Se sugirió una cirugía exploradora, pero la paciente no aceptó. Se la trató con ciclosporina y metilprednisolona por enfermedad primaria. No se utilizó rituximab por reglas de su cobertura médica. La paciente tuvo una excelente respuesta al tratamiento de forma rápida. Los esteroides se disminuyeron de forma progresiva y se suspendieron a los seis meses, y la ciclosporina, a los doce meses. Durante los 36 meses de seguimiento sin medicación no ha habido recidiva ni signos de cáncer. Incluso cuando existen grandes probabilidades de que se trate de una nefropatía membranosa asociada a cáncer, aún es posible que se trate de una enfermedad primaria. Es necesario contar con mejores marcadores de nefropatía membranosa asociada a cáncer. Un nivel elevado de CA-125 no necesariamente es indicador de cáncer.

18.
Article in Chinese | WPRIM | ID: wpr-734918

ABSTRACT

Objective To report the spontaneous remission and induced remission of phospholipase A2 receptor (PLA2R)-associated idiopathic membranous nephropathy (IMN) in adults,as well as to explore the potential prognostic factors.Methods A total of 120 patients with IMN in Huashan Hospital during 2012 and 2017 were enrolled and their clinical data were collected.Results PLA2R-associated IMN patients accounted for 89.2% of the IMN patients.Spontaneous remission occurred in 35.5% of PLA2R-associated IMN patients.The patients with higher serum albumin and lower level of PLA2R antibody were more likely to achieve spontaneous remission (both P < 0.05).Multivariate logistic regression analysis showed that male was an independent risk factor for spontaneous remission in PLA2R-associated IMN patients (OR=0.060,95%CI 0.007-0.493,P=0.009),while higher serum albumin at baseline (OR=1.480,95% CI 1.144-1.932,P=0.004) and the improvement of serum albumin after 3 months' non-immunosuppressive treatment (OR=2.040,95%CI 1.322-3.151,P=0.001) were independent protective factors for spontaneous remission.About 42.1% PLA2R-associated IMN patients had received immunosuppressive therapy,with induced remission rate being 70.7%.High serum albumin before treatment was an independent protective factor for induced remission (OR=1.268,95% CI 1.014-1.585,P=0.038).Conclusions PLA2R-associated IMN accounts for most of the IMN patients,with a spontaneous remission rate of 35.5%,during the follow-up period,which is even higher in patients with higher baseline serum albumin and lower PLA2R antibody titer.Induced remission rate is 70.7% in patients in need of immunosuppresants.The serum albumin level may be helpful in predicting spontaneous remission and response to immunosuppressive therapy.

19.
Article in Chinese | WPRIM | ID: wpr-802239

ABSTRACT

Objective: To detect the effect of modified Shengjiangsan on the expression of reactive oxygen species(ROS) in mitochondria of renal foot cells of rats, in order to study the mechanism of modified Shengjiangsan. Method: After be fed for 7 days,the 60 SD male rats were randomly divided into four groups:blank control group, model group, positive medicine group and traditional Chinese medicine(TCM) treatment group. After establishment of the rat model of membranous nephropathy, model group, positive medicine group and TCM treatment group were treated differently. After 4 weeks, all of the rats were put to death, and the expressions of ROS, 24-hour urinary protein quantity,total cholesterol,triglyceride,total protein,albumin,urea nitrogen,creatinine were detected by Real-time fluorescence quantitative polymerase chain reaction Real-time PCR. Result: The expression of 24-hour urinary protein quantity,total cholesterol,triglyceride in positive medicine group and TCM treatment group were reduced,and the expressions of total protein,albumin in positive medicine group and TCM treatment group were reduced compared with those of model group (PPConclusion: Modified Shengjiangsan can effectively control the development of ROS in mitochondria of renal foot cells of rats, and repair the renal function of membranous nephropathy rats by recovering foot cells.

20.
Article in Chinese | WPRIM | ID: wpr-849878

ABSTRACT

Membranous nephropathy (MN) is the most common pathological type of adult nephrotic syndrome (NS), the venous thromboembolism is a common and severe complication making as high as 10% of annual mortality in MN. Prevention of thrombosis is one of the issues needing attention in treatment of MN. The hypercoagulable thrombus in MN is recognized in the field of nephrology, but there are still some controversies about the mechanism of hypercoagulable state caused by coagulation disorder and the anticoagulation treatment scheme. First, it is known that MN hypercoagulable thrombus is related to the state of nephrotic syndrome and its own pathological characteristics, and whether other factors existed is still unclear. Second, it is still controversial whether or not to implement preventive anticoagulation and when to begin anticoagulation in MN patients without thrombus. Plasma albumin is an independent risk factor for thromboembolism in patients with MN, and the risk of thrombosis increases significantly with the decrease of albumin. The guidelines recommend anticoagulant therapy for patients with MN less than 25g/L. There are some shortcomings in the application of anticoagulants recommended in clinical practice and guidelines in MN, and the new application of direct oral anticoagulants (DOAC) in clinical practice in MN lacks effective evidence. How to choose the most suitable anticoagulant is the third problem that nephrologist faces when treating MN. Based on the specific pathological types of MN in NS, the research progress at home and abroad has been reviewed in present paper of the pathogenesis of coagulation disorder in MN, time to initiate preventive anticoagulation and selection of anticoagulant drugs in membranous NS.

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