Objective: To evaluate the effect of Poria cocos(Schw.) Wolf hydroethanolic extract(PHE) against nephrotic syndrome(NS) in rats and to identify the potential active components from PHE. Methods: The high content compo...Objective: To evaluate the effect of Poria cocos(Schw.) Wolf hydroethanolic extract(PHE) against nephrotic syndrome(NS) in rats and to identify the potential active components from PHE. Methods: The high content compounds were isolated and purified by using column chromatography followed by preparative highperformance liquid chromatography(p-HPLC). Forty male Wistar rats with adriamycin(ADR)-induced NS were randomly divided into 5 groups, 8 in each group: model control group, positive control group(with prednisone treatment), PHE low-dose group, PHE middle-dose group and PHE high-dose group. Another 8 rats were recruited as vehicle control group. All rats received the intragastric administration of corresponding drugs or saline for 30 days. During the experimental period, rats’ behavior and appearance were observed and recorded daily, and their body weights were recorded weekly. After treatment, 24-h urine samples were collected to evaluate the urine protein and urine creatinine(Ucr); then the rats were sacrificed to collect carotid blood and to determine the levels of serum total protein(TP), albumin(Alb), globulin(Glo), total cholesterol(TC) and cytokine interlukin-4(IL-4). Results: Six acidic components were isolated and identified from the PHE section: pachymic acid, 15α-hydroxydehydrotumulosic acid, trametenolic acid, dehydropachymic acid, 3β-hydroxy-lanosta-7,9(11), 24-trien-21-oic-acid and dehydroeburicoic acid. Compared with the model control group, the urine protein content were significantly decreased in the PHE treatment groups and positive control group(P<0.05), especially PHE middle-dose group(P<0.01). The Ucr values and serum levels of TP, Glo, TC and IL-4 in PHE low-and middle-dose groups were also presented obvious recover tendency as compared with the model control group(P<0.05 or P<0.01). However, positive control group and all PHE groups indicated no significant therapeutic effect on raising Alb value, although PHE low-and middle-dose treatment groups showed better outcomes than positive co展开更多
Objective To investigate the efficacy and safety of rituximab(RTX) in the treatment of idiopathic membranous nephropathy(IMN) with nephrotic syndrome with a systematic review and meta-analysis.Methods Pub Med, Embase,...Objective To investigate the efficacy and safety of rituximab(RTX) in the treatment of idiopathic membranous nephropathy(IMN) with nephrotic syndrome with a systematic review and meta-analysis.Methods Pub Med, Embase, Cochrane Library and Clinical Trials(December 2016) were searched to identify researches investigating the treatment of RTX in adult patients with biopsy-proven IMN. Complete remission(CR) or partial remission was regarded as effective therapy, and the cumulated remission rate was calculated.Results Seven studies involved 120 patients(73% were men) were included in our systematic review and metaanalysis. All were prospective observation cohort studies or matched-cohort studies, mainly came from two medical centers, and one study was multi-centric(four nephrology units in northern Italy). The creatinine clearance was more than 20 ml/(min·1.73 m2) and persistent proteinuria higher than 3.5 g/d for at least 6 months. All patients received treatment previously [44(36.7%) had immunosuppressive treatment]. In 12-and 24-month, 56%(95%CI, 0.47-0.65) and 68%(95%CI, 0.41-0.87) patients could reach remission, while 15%(95%CI, 0.09-0.23) and 20%(95%CI, 0.12-0.32) patients could reach CR. The reduction in proteinuria was gradual and obvious, paralleled with upward trend of serum albumin level and decreasing serum cholesterol level. Renal functions were stable. Relapses happened in 24 months were around 8%. RTX related adverse events were mild and were mostly infusion-related reactions.Conclusions RTX treatment in IMN was efficient, well tolerated and safe. More than 60% patients can reach partial remission or CR in 24 months, and relapse is rare. Adverse events of RTX are mostly infusion-related reactions and generally mild.展开更多
To evaluate the balance status of interleukin 18 （IL-18） and interleukin 18 binding protein （IL-18BP） in circulation in patients with lupus nephritis （LN） and primary nephrotic syndrome （PNS）, plasma levels as...To evaluate the balance status of interleukin 18 （IL-18） and interleukin 18 binding protein （IL-18BP） in circulation in patients with lupus nephritis （LN） and primary nephrotic syndrome （PNS）, plasma levels as well as mRNA expression in peripheral blood mononuclear cells （PBMCs） of IL-18 and IL-18BP were measured by ELISA and RT-PCR respectively. The ratio of IL-18/IL-18BP was also calculated. Both plasma IL-18 and IL-18BP increased significantly in LN patients while only IL-18BP increased in PNS, which resulted in an elevated ratio of IL-18/IL-18BP in LN but not in PNS patients when compared with normal controls. In contrast, increased level of IL-18 mRNA was only detected in LN but not in PNS group, although IL-18BP mRNA expressions in PBMCs in both groups were higher than that in control. The imbalance of IL-18 and IL-18BP might be involved in the pathogenesis of LN, based on which a therapeutic approach is valuable to be developed for LN.展开更多
Background Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children,with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities.The etiological factors ...Background Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children,with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities.The etiological factors and mechanisms of childhood idiopathic nephrotic syndrome have not yet been fully elucidated.This review summarizes the progress of the immunopathogenesis of idiopathic nephrotic syndrome in children.Data sources We review the literature on the immunopathogenesis of idiopathic nephrotic syndrome in children.Databases including Medline,Scopus,and Web of Science were searched for studies published in any language with the terms"chil-dren","idiopathic nephrotic syndrome","immunopathogenesis","T cells","circulating permeability factors",and"B cells".Results Dysfunction in T lymphocytes and pathogenic circulatory factors were indicated to play key roles in the pathogenesis of idiopathic nephrotic syndrome.Recently,some studies have shown that cellular immune dysfunction may also be involved in the pathogenesis of idiopathic nephrotic syndrome.Conclusions Both T-and B-cell dysfunction may play significant roles in the pathogenesis of idiopathic nephrotic syndrome,like two sides of one coin,but the role of B cell seems more important than T cells.展开更多
Objective： To provide an objective reference for the syndrome types of Chinese medicine（CM） associated with pediatric primary nephrotic syndrome（PNS）.Methods： A cross-sectional study was performed.Data on clinic...Objective： To provide an objective reference for the syndrome types of Chinese medicine（CM） associated with pediatric primary nephrotic syndrome（PNS）.Methods： A cross-sectional study was performed.Data on clinical symptoms,CM syndrome types,biochemical indices,and medications used were collected from 98 children with PNS.Then,the correlation between CM syndromes and biochemical indices,as well as medications used,was analyzed.Results： The four most common symptoms in children with PNS were brown urine,red tongue,excessive sweating,and swelling of the face and limbs.The syndromes of qi deficiency of Fei（Lung） and Shen（Kidney）（FSQD） and yin deficiency of Gan（Liver） and Shen（GSYD） were the most common main CM syndrome types.FSQD syndrome score correlated significantly with the total cholesterol level,urine protein/creatinine ratio,and urine Ig G and albumin levels（P〈0.01 or P〈0.05）.The use of maintenance glucocorticoids combined with immunosuppressive agents correlated with FSQD syndrome,and the use of maintenance glucocorticoids alone correlated with GSYD syndrome（P〈0.05）.Conclusion： Two of the most common CM syndrome types were FSQD and GSYD syndromes.FSQD syndrome may be caused by some factors related to lipid levels,protein loss,and the use of immunosuppressive agents.The use of maintenance glucocorticoids may cause GSYD syndrome.展开更多
Objective:To investigate the effect of prostaglandin E1 (PGE1) (Alprostadii injection) on patients with primary nephrotic syndrome(PNS). Methods: 37 patients with PNS were recruited to study the effect of prostaglandi...Objective:To investigate the effect of prostaglandin E1 (PGE1) (Alprostadii injection) on patients with primary nephrotic syndrome(PNS). Methods: 37 patients with PNS were recruited to study the effect of prostaglandin E1 on platelet aggregation function [ PAG (5,) PAG( m ) ], serum total protein (TP) , albumin (Al),blood urea nitrogen(BUN) ,serum creatinine(Scr) ,cholesterol(CHO), triglyceride(TG), protein in 24-hour urine (Pr/24h) and platelet account (PLT). Results: TP, Al, CHO, TG, BUN, Scr, Pr/24h, PAG(5) and PAG(m) in PNS group before treatment were significantly different from those in control group(P＜0.05, P＜0.01) while no significant difference was found for PLT. When treated with PGE1 , TP,Al,CHO, TG, Pr/24h, ADP- induced PAG(5) ,and Adr- induced PAG(5) and PAG(m) were significantly different from those before treatment (P＜0.05). Adr- induced PAG(5) and PAG(m) were significantly different. Adr- induced PAG(5) was xsitively correlated with BUN and Scr in PNS(P＜0.01). Similar correlation was found between ADP-induced PAG(5) and Al ,BUN,Scr,Pr/24h(P＜0.05), AD- induced PAG(m) and TP,CHO(P＜0.05). Conclusions: PGE1 may be an effective drug for the treatment for hypercoagulation in patients with PNS.展开更多
Background Cyclosporine is effective in treating nephrotic syndrome （NS） with idiopathic membranous nephropathy （IMN） in adults. But high relapse rate remains a major concern. The way to manipulate cyclosporine is...Background Cyclosporine is effective in treating nephrotic syndrome （NS） with idiopathic membranous nephropathy （IMN） in adults. But high relapse rate remains a major concern. The way to manipulate cyclosporine is inconclusive. The aim of this study was to introduce the way how to titrate the cyclosporine to maintain complete remission without relapse. Methods Patients with biopsy-proven IMN with NS treated with cyclosporine for at least 1 month from 1996 to 2011 at Peking Union Medical College Hospital were reviewed. Results Mean age of the 51 eligible patients was 52 years, with 39 men. Mean proteinuria was （7.47±3.14） g/d, serum albumin （24.50±6.29） g/L, and serum creatinine （82.62±21.18） μmol/L. Cyclosporine was commenced at a mean dose of （3.46±0.63） mg·kg^-1·d^-1. Oral prednisone （0.40±0.29） mg·kg^-1·d^-1 was given concomitantly in 38 patients. Cyclosporine was administered for a median of 16 months （range 1-93 months） and stopped in non-responders by month six. By month 3 （n=47）, the number in complete remission （CR） and partial remission （PR） was 3 and 24, which shifted to 12 and 17 by month 6 （n=41）. Male gender, heavy proteinuria, low serum albumin level, and high serum creatinine level were significant determinants in poor response by month six （P 〈0.05 in all variables compared with responders）. There was a significant reversible serum creatinine increase within 25% during month 3 to 12 （P 〈0.05 in all variables compared with baseline value）. Eleven patients maintained cyclosporine for more than 24 months with a cyclosporine dose of （1.04±1.06） mg·kg^-1·d^-1. Nine patients were in CR. Renal function, systolic and diastolic blood pressure remained stable. Renal impairment （〉30% rise of serum creatinine）, secondary infection, hypertension, gingival hyperplasia and liver impairment occurred in 6, 4, 10, 4, and 1 patients, respectively. Conclusions The observation time for cyclosporine to effectively induce CR of NS in IMN 展开更多
Background Renal biopsy is necessary for diagnosing the pathological changes of primary nephrotic syndrome （NS）. However, it is invasive, time-consuming and can not be performed frequent on the same patient. Thus, d...Background Renal biopsy is necessary for diagnosing the pathological changes of primary nephrotic syndrome （NS）. However, it is invasive, time-consuming and can not be performed frequent on the same patient. Thus, development of a non-invasive and rapid diagnostic method may improve clinical patient management. Methods Proteomic tool magnetic bead-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MB-based MALDI TOF MS） was applied to serum to determine peptidome patterns that are characteristic of different pathological changes. Results Serum specimen from 114 patients with NS （62 were minimal change disease （MCD）, 30 were membranous nephropathy （MN）, and 22 were focal segmental glomerulosclerosis （FSGS）） and 60 normal individuals were analyzed using MB-based MALDI TOF MS. The peptidome pattern was generated by genetic algorithms using a training set of 31 MCD, 15 MN, 11 FSGS and 30 normal individuals and was validated by an independent testing set of the remaining samples. The serum peptidome pattern, based on a panel of 14 peaks, accurately recognized samples from MCD, MN, FSGS and healthy control with sensitivities of 93.5%, 86.7%, 63.6% and 90.0%, and specificities of 98.2%, 94.4%, 100% and 89.5%, respectively. Moreover, one peptide from peptidome pattern was identified by liquid chromatography tandem mass spectrometry （LC MS/MS） as fibrinogen A. Conclusion Detection of the serum peptidome pattern is a rapid, non-invasive, high-throughout, and reproducible method for identifying the pathological patterns of patients with nephrotic syndrome.展开更多
To investigate the mechanism of lipid lowering effect of the Astragalus mongholicus and Angelica sinensis compound (A&A) on nephrotic hyperlipidemia in rats Methods Rats with nephrotic syndrome from acc...To investigate the mechanism of lipid lowering effect of the Astragalus mongholicus and Angelica sinensis compound (A&A) on nephrotic hyperlipidemia in rats Methods Rats with nephrotic syndrome from accelerated nephrotoxic serum nephritis were used They were divided into two groups: A&A treatment group and nephrotic control group Normal rats were used as a normal control group Serum lipids, serum lipoprotein lipase (LPL) and lecithin cholesterol acyltransferase (LCAT) were assayed biochemically and enzymatically mRNAs of hepatic hydroxy methyl glutaryl CoA reductase (HMG CoA R) and low density lipoprotein receptor (LDL R) were assessed by Northern blot Results In nephrotic control group hyperlipidemia was found The activities of serum LPL and LCAT were low Hepatic HMG CoA R mRNA increased temporarily at the early stage while LDL R mRNA decreased gradually In A&A treatment group, serum total cholesterol (TC), triglyceride (TG), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were significantly lower than those in nephrotic control group There was no change in the amount of hepatic HMG CoA R mRNA, but hepatic LDL R mRNA and activities of serum LPL and LCAT increased significantly Conclusions A&A alleviates hyperlipidemia consider^ably in nephrotic rats A&A improves disorders of lipid metabolism perhaps through up regulating the expression of hepatic LDL R gene and through increasing the activities of serum LPL and LCAT展开更多
Background Congenital and infantile nephrotic syndrome (CNS and INS) are rare inherited defects in glomerular filtration involving a variety of gene mutations.This study aimed to analyze all genetic mutations associat...Background Congenital and infantile nephrotic syndrome (CNS and INS) are rare inherited defects in glomerular filtration involving a variety of gene mutations.This study aimed to analyze all genetic mutations associated with congenital and infantile nephrotic syndrome treated at our institution.We also discussed our different approach secondary to culture and resources.Methods A retrospective single-center study of all children diagnosed as NS before the age of l year over a duration of over one decade.Results Twenty-nine children (12 boys) were included in the study.Their median age (range) was 2.4 (0.1-12) months (20 CNS and 9 INS).Consanguinity was present in 90% of children.The genetic analysis' results were only available for 20 children.An underlying causative homozygous mutation was detected in 18 children (90%):NPHS1 (9),NPHS2(2),LAMB2(3),PLCE1(1),WT1(1),and ITSN1 novel mutation (2).One child had heterozygous mutation of NPHS2 and another child had heterozygous mutation of NPHS1 which could not explain the disease.All CNS cases were all managed with intermittent intravenous albumin infusion,ACEi,diuretics,and indomethacin.None of the children were managed by nephrectomy followed by peritoneal dialysis (PD) because of limited resources.Only one child achieved partial remission,while 15 children died at a median (range) age of 5.8 (1.25-29) months.The remaining 14 children were followed up for an average of 36 (3.9-120) months.Three children progressed to end-stage kidney disease and PD was performed in only two children.Conclusions NPHS1 is the main underlying cause of CNS and INS in our study population.CNS and INS were associated with high morbidity and mortality.展开更多
Background:Congenital nephrotic syndrome(CNS),defined as heavy proteinuria,hypoalbuminemia,hyperlipidemia and edema presenting in the first 0-3 months of life,may be caused by congenital syphilis,toxoplasmosis,or cong...Background:Congenital nephrotic syndrome(CNS),defined as heavy proteinuria,hypoalbuminemia,hyperlipidemia and edema presenting in the first 0-3 months of life,may be caused by congenital syphilis,toxoplasmosis,or congenital viral infections(such as cytomegalovirus).However,the majority of CNS cases are caused by monogenic defects of structural proteins that form the glomerular fi ltration barrier in the kidneys.Since 1998,an increasing number of genetic defects have been identifi ed for their involvements in the pathogenesis of CNS,including NPHS1,NPHS2,WT1,PLCE1,and LAMB2.Data sources:We searched databases such as PubMed,Elsevier and Wanfang with the following key words:congenital nephrotic syndrome,proteinuria,infants,neonate,congenital infection,mechanism and treatment;and we selected those publications written in English that we judged to be relevant to the topic of this review.Results:Based on the data present in the literature,we reviewed the following topics:1)Infection associated CNS including congenital syphilis,congenital toxoplasmosis,and congenital cytomegalovirus infection;2)genetic CNS including mutation of NPHS1(Nephrin),NPHS2(Podocin),WT1,LAMB2(Laminin-β2),PLCE1(NPHS3);3)Other forms of CNS including maternal systemic lupus erythematosus,mercury poisoning,renal vein thrombosis,neonatal alloimmunization against neutral endopeptidase.Conclusions:At present,the main challenge in CNS is to identify the cause of disease for individual patients.To make a definitive diagnosis,with the exclusion of infection-related CNS and maternal-associated disorders,pathology,family history,inheritance mode,and other accompanying congenital malformations are sometimes,but not always,useful indicators for diagnosing genetic CNS.Next-generation sequencing would be a more effective method for diagnosing genetic CNS in some patients,however,there are still some challenges with next-generation sequencing that need to be resolved in the future.展开更多
BACKGROUND The interaction between the kidney and the thyroid is important for normal function of both organs.In nephrotic syndrome,proteinuria leads to loss of several proteins,which in turn causes hypothyroidism.AIM...BACKGROUND The interaction between the kidney and the thyroid is important for normal function of both organs.In nephrotic syndrome,proteinuria leads to loss of several proteins,which in turn causes hypothyroidism.AIM To assess the thyroid function in children with nephrotic syndrome.METHODS This cross-sectional study was conducted in a tertiary center,Bhopal,from February 2020 to January 2021.Consecutive children aged 1-15 years admitted with nephrotic syndrome(first-time diagnosed and all relapse cases)were included in the study.A thyroid profile was sent along with routine investigations,and thyroid hormone status was assessed in nephrotic syndrome children.RESULTS Of the 70 patients,39(55.7%)showed abnormal thyroid profiles;19(27.1%)had overt hypothyroidism,and 20(28.6%)had subclinical hypothyroidism.Overt hypothyroidism was seen in 16.1%of newly diagnosed cases,40%of second relapses,and 2.7%of frequently relapsed cases(P<0.001).The mean serum free T3 and free T4 levels in frequent relapses were 2.50±0.39 ng/dL and 0.78±0.12 ng/dL,respectively,which were significantly lower than in newly diagnosed cases(2.77±0.37 ng/dL and 0.91±0.19 ng/dL,respectively).The mean thyroidstimulating hormone(TSH)level was significantly higher in frequent relapses (5.86±1.56μIU/mL)and second relapse(5.81±1.78μIU/mL)than in newly diagnosed cases(4.83±0.76μIU/mL)and first relapse cases(4.74±1.17μIU/mL),(P<0.01).CONCLUSION An abnormal thyroid profile was commonly observed in children with nephrotic syndrome,and overt hypothyroidism was more common in frequent relapse cases.Therefore,thyroid screening should be a part of the management of nephrotic syndrome so that hypothyroidism can be detected and managed at an early stage.展开更多
Nephrotic syndrome(NS) is the most common glomerular disease of childhood. Steroid-dependent and steroid-resistant nephrotic syndrome present challenges in their pharmaceutical management; patients may need several im...Nephrotic syndrome(NS) is the most common glomerular disease of childhood. Steroid-dependent and steroid-resistant nephrotic syndrome present challenges in their pharmaceutical management; patients may need several immunosuppressive medication for optimum control, each of which medication has its own safety profile. Rituximab(RTX) is a monoclonal antibody that targets B cells and has been used successfully for management of lymphoma and rheumatoid arthritis. Recent clinical studies showed that rituximab may be an efficacious and safe alternative for the treatment of complicated nephrotic syndrome. In this review article, we aim to review the efficacy and safety of RTX therapy in nephrotic syndrome. We reviewed the literature pertaining to this topic by searching for relevant studies on Pub Med and Medline using specific keywords. The initial search yielded 452 articles. These articles were then examined to ensure their relevance to the topic of research. We focused on multicenter randomized controlled trials with relatively large numbers of patients. A total of 29 articles were finally identified and will be summarized in this review. The majority of clinical studies of RTX in complicated pediatric NS showed that rituximab is effective in approximately 80% of patients with steroid-dependent NS, as it decreases the number of relapses and steroid dosage. However, RTX is less effective at achieving remission in steroid-resistant NS. RTX use was generally safe, and most side effects were transient and infusion-related. More randomized, double-blinded clinical studies are needed to assess the role of RTX in children with nephrotic syndrome.展开更多
The pathogenesis of childhood primary nephrotic syndrome (PNS) is unclear. However, an immune mechanism has generally been accepted as a cause. Imbalance of T lymphocyte and a variety of inflammatory cytokines, chemot...The pathogenesis of childhood primary nephrotic syndrome (PNS) is unclear. However, an immune mechanism has generally been accepted as a cause. Imbalance of T lymphocyte and a variety of inflammatory cytokines, chemotactic and transcription factors are involved in the pathophysiology and manifestations of PNS,^(1,2) (and nuclear) factor kappa B (NF-κB) transcriptionally regulates the expression of these factors.~3 Research has been focused on NF-κB and inflammatory regulated mediators of renal diseases, but seldom on different clinical manifestations and histopathological changes. In order to explore a potential mechanism for the pathogenesis of PNS in children and a basis for preventing its advance, we determined NF-κB activity in the kidney of children with PNS in vitro using immunohistochemical staining and the multimedia coloured pathological image analysis system and its relations to clinical manifestations, histopathological changes and 24-hour urinary protein excretion.展开更多
Background:Cyclosporine A and tacrolimus(TAC)are often used as a second-line treatment for children with refractory nephrotic syndrome(NS).This study was undertaken to investigate the efficacy and safety of Tacrobell&...Background:Cyclosporine A and tacrolimus(TAC)are often used as a second-line treatment for children with refractory nephrotic syndrome(NS).This study was undertaken to investigate the efficacy and safety of Tacrobell®,a locally produced generic form of TAC.Methods:This study was a one-year prospective,open-label,single-arm,multicenter trial.Fourty-four children with steroid-dependent NS(SDNS)and 33 children with steroid-resistant NS(SRNS)were enrolled.The primary endpoints were defined as the remission rates,whereas the secondary endpoints were recognized as the duration of remission and adverse effects of TAC.Results:After one-year treatment,34(77.3%)of the 44 patients with SDNS were in complete remission,and 6(13.6%)were in partial remission.Nineteen(43.2%)patients did not relapse during the study;for those who did relapse,the mean duration of remission was 4.6±2.9 months.The number of relapse episodes during the study period(0.90 per patient-year)was significantly lower than that in the preceding year(2.8 per patientyear).After treatment for 3 and 6 months,12(36.4%)of the 33 patients with SRNS were in remission,and after treatment for 12 months,the number of patients had increased to 13(39.4%).The mean time to achieve remission was 4.0±3.2 months.After remission(duration,3.7±2.7 months),12(54.5%)of 22 patients relapsed.The fasting blood glucose and blood pressure levels during the therapy were similar to those at the time of study entry.Conclusions:Treatment with Tacrobell®was effective and safe for children with refractory NS.The efficacy of this generic form of TAC was better than that of the original TAC formula.展开更多
基金Supported by the National Natural Science Foundation of China(No.30970295)Youth Fund Project of Hubei Provincial Department of Education(No.Q20091606),China
文摘Objective: To evaluate the effect of Poria cocos(Schw.) Wolf hydroethanolic extract(PHE) against nephrotic syndrome(NS) in rats and to identify the potential active components from PHE. Methods: The high content compounds were isolated and purified by using column chromatography followed by preparative highperformance liquid chromatography(p-HPLC). Forty male Wistar rats with adriamycin(ADR)-induced NS were randomly divided into 5 groups, 8 in each group: model control group, positive control group(with prednisone treatment), PHE low-dose group, PHE middle-dose group and PHE high-dose group. Another 8 rats were recruited as vehicle control group. All rats received the intragastric administration of corresponding drugs or saline for 30 days. During the experimental period, rats’ behavior and appearance were observed and recorded daily, and their body weights were recorded weekly. After treatment, 24-h urine samples were collected to evaluate the urine protein and urine creatinine(Ucr); then the rats were sacrificed to collect carotid blood and to determine the levels of serum total protein(TP), albumin(Alb), globulin(Glo), total cholesterol(TC) and cytokine interlukin-4(IL-4). Results: Six acidic components were isolated and identified from the PHE section: pachymic acid, 15α-hydroxydehydrotumulosic acid, trametenolic acid, dehydropachymic acid, 3β-hydroxy-lanosta-7,9(11), 24-trien-21-oic-acid and dehydroeburicoic acid. Compared with the model control group, the urine protein content were significantly decreased in the PHE treatment groups and positive control group(P<0.05), especially PHE middle-dose group(P<0.01). The Ucr values and serum levels of TP, Glo, TC and IL-4 in PHE low-and middle-dose groups were also presented obvious recover tendency as compared with the model control group(P<0.05 or P<0.01). However, positive control group and all PHE groups indicated no significant therapeutic effect on raising Alb value, although PHE low-and middle-dose treatment groups showed better outcomes than positive co
基金Supported by the Key Projects in the National Science and Technology Pillar Program during the Twelfth Five-year Plan Period(2011BAI10B03)
文摘Objective To investigate the efficacy and safety of rituximab(RTX) in the treatment of idiopathic membranous nephropathy(IMN) with nephrotic syndrome with a systematic review and meta-analysis.Methods Pub Med, Embase, Cochrane Library and Clinical Trials(December 2016) were searched to identify researches investigating the treatment of RTX in adult patients with biopsy-proven IMN. Complete remission(CR) or partial remission was regarded as effective therapy, and the cumulated remission rate was calculated.Results Seven studies involved 120 patients(73% were men) were included in our systematic review and metaanalysis. All were prospective observation cohort studies or matched-cohort studies, mainly came from two medical centers, and one study was multi-centric(four nephrology units in northern Italy). The creatinine clearance was more than 20 ml/(min·1.73 m2) and persistent proteinuria higher than 3.5 g/d for at least 6 months. All patients received treatment previously [44(36.7%) had immunosuppressive treatment]. In 12-and 24-month, 56%(95%CI, 0.47-0.65) and 68%(95%CI, 0.41-0.87) patients could reach remission, while 15%(95%CI, 0.09-0.23) and 20%(95%CI, 0.12-0.32) patients could reach CR. The reduction in proteinuria was gradual and obvious, paralleled with upward trend of serum albumin level and decreasing serum cholesterol level. Renal functions were stable. Relapses happened in 24 months were around 8%. RTX related adverse events were mild and were mostly infusion-related reactions.Conclusions RTX treatment in IMN was efficient, well tolerated and safe. More than 60% patients can reach partial remission or CR in 24 months, and relapse is rare. Adverse events of RTX are mostly infusion-related reactions and generally mild.
基金supported by a grant from Guangdong Natural Science Foundation(5011589)a PhD scholarship of Guangdong Medical College(200301).
文摘To evaluate the balance status of interleukin 18 （IL-18） and interleukin 18 binding protein （IL-18BP） in circulation in patients with lupus nephritis （LN） and primary nephrotic syndrome （PNS）, plasma levels as well as mRNA expression in peripheral blood mononuclear cells （PBMCs） of IL-18 and IL-18BP were measured by ELISA and RT-PCR respectively. The ratio of IL-18/IL-18BP was also calculated. Both plasma IL-18 and IL-18BP increased significantly in LN patients while only IL-18BP increased in PNS, which resulted in an elevated ratio of IL-18/IL-18BP in LN but not in PNS patients when compared with normal controls. In contrast, increased level of IL-18 mRNA was only detected in LN but not in PNS group, although IL-18BP mRNA expressions in PBMCs in both groups were higher than that in control. The imbalance of IL-18 and IL-18BP might be involved in the pathogenesis of LN, based on which a therapeutic approach is valuable to be developed for LN.
基金This study was supported by the National Natural Foundation of China(81770710)Key Research and Development Plan of Zhejiang Province(2019C03028)the Major projects jointly constructed by the Zhejiang Province,and National Health Commission(WKJ-ZJ-1908).
文摘Background Idiopathic nephrotic syndrome is a common form of glomerular nephropathy in children,with an incidence rate of 1.15-16.9/100,000 depending on different nationalities and ethnicities.The etiological factors and mechanisms of childhood idiopathic nephrotic syndrome have not yet been fully elucidated.This review summarizes the progress of the immunopathogenesis of idiopathic nephrotic syndrome in children.Data sources We review the literature on the immunopathogenesis of idiopathic nephrotic syndrome in children.Databases including Medline,Scopus,and Web of Science were searched for studies published in any language with the terms"chil-dren","idiopathic nephrotic syndrome","immunopathogenesis","T cells","circulating permeability factors",and"B cells".Results Dysfunction in T lymphocytes and pathogenic circulatory factors were indicated to play key roles in the pathogenesis of idiopathic nephrotic syndrome.Recently,some studies have shown that cellular immune dysfunction may also be involved in the pathogenesis of idiopathic nephrotic syndrome.Conclusions Both T-and B-cell dysfunction may play significant roles in the pathogenesis of idiopathic nephrotic syndrome,like two sides of one coin,but the role of B cell seems more important than T cells.
基金Supported by Shanghai Municipal Commission of Health and Family Planning(No.2010QL031B)
文摘Objective： To provide an objective reference for the syndrome types of Chinese medicine（CM） associated with pediatric primary nephrotic syndrome（PNS）.Methods： A cross-sectional study was performed.Data on clinical symptoms,CM syndrome types,biochemical indices,and medications used were collected from 98 children with PNS.Then,the correlation between CM syndromes and biochemical indices,as well as medications used,was analyzed.Results： The four most common symptoms in children with PNS were brown urine,red tongue,excessive sweating,and swelling of the face and limbs.The syndromes of qi deficiency of Fei（Lung） and Shen（Kidney）（FSQD） and yin deficiency of Gan（Liver） and Shen（GSYD） were the most common main CM syndrome types.FSQD syndrome score correlated significantly with the total cholesterol level,urine protein/creatinine ratio,and urine Ig G and albumin levels（P〈0.01 or P〈0.05）.The use of maintenance glucocorticoids combined with immunosuppressive agents correlated with FSQD syndrome,and the use of maintenance glucocorticoids alone correlated with GSYD syndrome（P〈0.05）.Conclusion： Two of the most common CM syndrome types were FSQD and GSYD syndromes.FSQD syndrome may be caused by some factors related to lipid levels,protein loss,and the use of immunosuppressive agents.The use of maintenance glucocorticoids may cause GSYD syndrome.
基金This work is supported by grant from Beijing Tide Pharmaceutical Co,Ltd.
文摘Objective:To investigate the effect of prostaglandin E1 (PGE1) (Alprostadii injection) on patients with primary nephrotic syndrome(PNS). Methods: 37 patients with PNS were recruited to study the effect of prostaglandin E1 on platelet aggregation function [ PAG (5,) PAG( m ) ], serum total protein (TP) , albumin (Al),blood urea nitrogen(BUN) ,serum creatinine(Scr) ,cholesterol(CHO), triglyceride(TG), protein in 24-hour urine (Pr/24h) and platelet account (PLT). Results: TP, Al, CHO, TG, BUN, Scr, Pr/24h, PAG(5) and PAG(m) in PNS group before treatment were significantly different from those in control group(P＜0.05, P＜0.01) while no significant difference was found for PLT. When treated with PGE1 , TP,Al,CHO, TG, Pr/24h, ADP- induced PAG(5) ,and Adr- induced PAG(5) and PAG(m) were significantly different from those before treatment (P＜0.05). Adr- induced PAG(5) and PAG(m) were significantly different. Adr- induced PAG(5) was xsitively correlated with BUN and Scr in PNS(P＜0.01). Similar correlation was found between ADP-induced PAG(5) and Al ,BUN,Scr,Pr/24h(P＜0.05), AD- induced PAG(m) and TP,CHO(P＜0.05). Conclusions: PGE1 may be an effective drug for the treatment for hypercoagulation in patients with PNS.
文摘Background Cyclosporine is effective in treating nephrotic syndrome （NS） with idiopathic membranous nephropathy （IMN） in adults. But high relapse rate remains a major concern. The way to manipulate cyclosporine is inconclusive. The aim of this study was to introduce the way how to titrate the cyclosporine to maintain complete remission without relapse. Methods Patients with biopsy-proven IMN with NS treated with cyclosporine for at least 1 month from 1996 to 2011 at Peking Union Medical College Hospital were reviewed. Results Mean age of the 51 eligible patients was 52 years, with 39 men. Mean proteinuria was （7.47±3.14） g/d, serum albumin （24.50±6.29） g/L, and serum creatinine （82.62±21.18） μmol/L. Cyclosporine was commenced at a mean dose of （3.46±0.63） mg·kg^-1·d^-1. Oral prednisone （0.40±0.29） mg·kg^-1·d^-1 was given concomitantly in 38 patients. Cyclosporine was administered for a median of 16 months （range 1-93 months） and stopped in non-responders by month six. By month 3 （n=47）, the number in complete remission （CR） and partial remission （PR） was 3 and 24, which shifted to 12 and 17 by month 6 （n=41）. Male gender, heavy proteinuria, low serum albumin level, and high serum creatinine level were significant determinants in poor response by month six （P 〈0.05 in all variables compared with responders）. There was a significant reversible serum creatinine increase within 25% during month 3 to 12 （P 〈0.05 in all variables compared with baseline value）. Eleven patients maintained cyclosporine for more than 24 months with a cyclosporine dose of （1.04±1.06） mg·kg^-1·d^-1. Nine patients were in CR. Renal function, systolic and diastolic blood pressure remained stable. Renal impairment （〉30% rise of serum creatinine）, secondary infection, hypertension, gingival hyperplasia and liver impairment occurred in 6, 4, 10, 4, and 1 patients, respectively. Conclusions The observation time for cyclosporine to effectively induce CR of NS in IMN
基金This work was supported by gran＇ts from the National Science Fund for Distinguished Young Scholars of China （No. 30925019）, the National Natural Science Foundation of China （No. 30871166）, and the Key Clinical Research Program, Ministry of Health, China （2007）.
文摘Background Renal biopsy is necessary for diagnosing the pathological changes of primary nephrotic syndrome （NS）. However, it is invasive, time-consuming and can not be performed frequent on the same patient. Thus, development of a non-invasive and rapid diagnostic method may improve clinical patient management. Methods Proteomic tool magnetic bead-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MB-based MALDI TOF MS） was applied to serum to determine peptidome patterns that are characteristic of different pathological changes. Results Serum specimen from 114 patients with NS （62 were minimal change disease （MCD）, 30 were membranous nephropathy （MN）, and 22 were focal segmental glomerulosclerosis （FSGS）） and 60 normal individuals were analyzed using MB-based MALDI TOF MS. The peptidome pattern was generated by genetic algorithms using a training set of 31 MCD, 15 MN, 11 FSGS and 30 normal individuals and was validated by an independent testing set of the remaining samples. The serum peptidome pattern, based on a panel of 14 peaks, accurately recognized samples from MCD, MN, FSGS and healthy control with sensitivities of 93.5%, 86.7%, 63.6% and 90.0%, and specificities of 98.2%, 94.4%, 100% and 89.5%, respectively. Moreover, one peptide from peptidome pattern was identified by liquid chromatography tandem mass spectrometry （LC MS/MS） as fibrinogen A. Conclusion Detection of the serum peptidome pattern is a rapid, non-invasive, high-throughout, and reproducible method for identifying the pathological patterns of patients with nephrotic syndrome.
基金This study was supported by the National Natural Science Foundation of China(No.39670909)and China Medical Board in NewYork
文摘To investigate the mechanism of lipid lowering effect of the Astragalus mongholicus and Angelica sinensis compound (A&A) on nephrotic hyperlipidemia in rats Methods Rats with nephrotic syndrome from accelerated nephrotoxic serum nephritis were used They were divided into two groups: A&A treatment group and nephrotic control group Normal rats were used as a normal control group Serum lipids, serum lipoprotein lipase (LPL) and lecithin cholesterol acyltransferase (LCAT) were assayed biochemically and enzymatically mRNAs of hepatic hydroxy methyl glutaryl CoA reductase (HMG CoA R) and low density lipoprotein receptor (LDL R) were assessed by Northern blot Results In nephrotic control group hyperlipidemia was found The activities of serum LPL and LCAT were low Hepatic HMG CoA R mRNA increased temporarily at the early stage while LDL R mRNA decreased gradually In A&A treatment group, serum total cholesterol (TC), triglyceride (TG), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were significantly lower than those in nephrotic control group There was no change in the amount of hepatic HMG CoA R mRNA, but hepatic LDL R mRNA and activities of serum LPL and LCAT increased significantly Conclusions A&A alleviates hyperlipidemia consider^ably in nephrotic rats A&A improves disorders of lipid metabolism perhaps through up regulating the expression of hepatic LDL R gene and through increasing the activities of serum LPL and LCAT
文摘Background Congenital and infantile nephrotic syndrome (CNS and INS) are rare inherited defects in glomerular filtration involving a variety of gene mutations.This study aimed to analyze all genetic mutations associated with congenital and infantile nephrotic syndrome treated at our institution.We also discussed our different approach secondary to culture and resources.Methods A retrospective single-center study of all children diagnosed as NS before the age of l year over a duration of over one decade.Results Twenty-nine children (12 boys) were included in the study.Their median age (range) was 2.4 (0.1-12) months (20 CNS and 9 INS).Consanguinity was present in 90% of children.The genetic analysis' results were only available for 20 children.An underlying causative homozygous mutation was detected in 18 children (90%):NPHS1 (9),NPHS2(2),LAMB2(3),PLCE1(1),WT1(1),and ITSN1 novel mutation (2).One child had heterozygous mutation of NPHS2 and another child had heterozygous mutation of NPHS1 which could not explain the disease.All CNS cases were all managed with intermittent intravenous albumin infusion,ACEi,diuretics,and indomethacin.None of the children were managed by nephrectomy followed by peritoneal dialysis (PD) because of limited resources.Only one child achieved partial remission,while 15 children died at a median (range) age of 5.8 (1.25-29) months.The remaining 14 children were followed up for an average of 36 (3.9-120) months.Three children progressed to end-stage kidney disease and PD was performed in only two children.Conclusions NPHS1 is the main underlying cause of CNS and INS in our study population.CNS and INS were associated with high morbidity and mortality.
基金supported by National Natural Science Foundation of China(Grant Nos.81270792,81470939 and 81170664)Zhejiang Provincial Natural Science Foundation of China(LH14H050002)+1 种基金Research Fund for the Doctoral Program of Higher Education of China(20120101110018)Zhejiang Provincial Healthy Science Foundation of China(2012KYA119,2014KYA123)。
文摘Background:Congenital nephrotic syndrome(CNS),defined as heavy proteinuria,hypoalbuminemia,hyperlipidemia and edema presenting in the first 0-3 months of life,may be caused by congenital syphilis,toxoplasmosis,or congenital viral infections(such as cytomegalovirus).However,the majority of CNS cases are caused by monogenic defects of structural proteins that form the glomerular fi ltration barrier in the kidneys.Since 1998,an increasing number of genetic defects have been identifi ed for their involvements in the pathogenesis of CNS,including NPHS1,NPHS2,WT1,PLCE1,and LAMB2.Data sources:We searched databases such as PubMed,Elsevier and Wanfang with the following key words:congenital nephrotic syndrome,proteinuria,infants,neonate,congenital infection,mechanism and treatment;and we selected those publications written in English that we judged to be relevant to the topic of this review.Results:Based on the data present in the literature,we reviewed the following topics:1)Infection associated CNS including congenital syphilis,congenital toxoplasmosis,and congenital cytomegalovirus infection;2)genetic CNS including mutation of NPHS1(Nephrin),NPHS2(Podocin),WT1,LAMB2(Laminin-β2),PLCE1(NPHS3);3)Other forms of CNS including maternal systemic lupus erythematosus,mercury poisoning,renal vein thrombosis,neonatal alloimmunization against neutral endopeptidase.Conclusions:At present,the main challenge in CNS is to identify the cause of disease for individual patients.To make a definitive diagnosis,with the exclusion of infection-related CNS and maternal-associated disorders,pathology,family history,inheritance mode,and other accompanying congenital malformations are sometimes,but not always,useful indicators for diagnosing genetic CNS.Next-generation sequencing would be a more effective method for diagnosing genetic CNS in some patients,however,there are still some challenges with next-generation sequencing that need to be resolved in the future.
文摘BACKGROUND The interaction between the kidney and the thyroid is important for normal function of both organs.In nephrotic syndrome,proteinuria leads to loss of several proteins,which in turn causes hypothyroidism.AIM To assess the thyroid function in children with nephrotic syndrome.METHODS This cross-sectional study was conducted in a tertiary center,Bhopal,from February 2020 to January 2021.Consecutive children aged 1-15 years admitted with nephrotic syndrome(first-time diagnosed and all relapse cases)were included in the study.A thyroid profile was sent along with routine investigations,and thyroid hormone status was assessed in nephrotic syndrome children.RESULTS Of the 70 patients,39(55.7%)showed abnormal thyroid profiles;19(27.1%)had overt hypothyroidism,and 20(28.6%)had subclinical hypothyroidism.Overt hypothyroidism was seen in 16.1%of newly diagnosed cases,40%of second relapses,and 2.7%of frequently relapsed cases(P<0.001).The mean serum free T3 and free T4 levels in frequent relapses were 2.50±0.39 ng/dL and 0.78±0.12 ng/dL,respectively,which were significantly lower than in newly diagnosed cases(2.77±0.37 ng/dL and 0.91±0.19 ng/dL,respectively).The mean thyroidstimulating hormone(TSH)level was significantly higher in frequent relapses (5.86±1.56μIU/mL)and second relapse(5.81±1.78μIU/mL)than in newly diagnosed cases(4.83±0.76μIU/mL)and first relapse cases(4.74±1.17μIU/mL),(P<0.01).CONCLUSION An abnormal thyroid profile was commonly observed in children with nephrotic syndrome,and overt hypothyroidism was more common in frequent relapse cases.Therefore,thyroid screening should be a part of the management of nephrotic syndrome so that hypothyroidism can be detected and managed at an early stage.
文摘Nephrotic syndrome(NS) is the most common glomerular disease of childhood. Steroid-dependent and steroid-resistant nephrotic syndrome present challenges in their pharmaceutical management; patients may need several immunosuppressive medication for optimum control, each of which medication has its own safety profile. Rituximab(RTX) is a monoclonal antibody that targets B cells and has been used successfully for management of lymphoma and rheumatoid arthritis. Recent clinical studies showed that rituximab may be an efficacious and safe alternative for the treatment of complicated nephrotic syndrome. In this review article, we aim to review the efficacy and safety of RTX therapy in nephrotic syndrome. We reviewed the literature pertaining to this topic by searching for relevant studies on Pub Med and Medline using specific keywords. The initial search yielded 452 articles. These articles were then examined to ensure their relevance to the topic of research. We focused on multicenter randomized controlled trials with relatively large numbers of patients. A total of 29 articles were finally identified and will be summarized in this review. The majority of clinical studies of RTX in complicated pediatric NS showed that rituximab is effective in approximately 80% of patients with steroid-dependent NS, as it decreases the number of relapses and steroid dosage. However, RTX is less effective at achieving remission in steroid-resistant NS. RTX use was generally safe, and most side effects were transient and infusion-related. More randomized, double-blinded clinical studies are needed to assess the role of RTX in children with nephrotic syndrome.
文摘The pathogenesis of childhood primary nephrotic syndrome (PNS) is unclear. However, an immune mechanism has generally been accepted as a cause. Imbalance of T lymphocyte and a variety of inflammatory cytokines, chemotactic and transcription factors are involved in the pathophysiology and manifestations of PNS,^(1,2) (and nuclear) factor kappa B (NF-κB) transcriptionally regulates the expression of these factors.~3 Research has been focused on NF-κB and inflammatory regulated mediators of renal diseases, but seldom on different clinical manifestations and histopathological changes. In order to explore a potential mechanism for the pathogenesis of PNS in children and a basis for preventing its advance, we determined NF-κB activity in the kidney of children with PNS in vitro using immunohistochemical staining and the multimedia coloured pathological image analysis system and its relations to clinical manifestations, histopathological changes and 24-hour urinary protein excretion.
基金supported by a grant from the Korean Health Technology R&D Project,Ministry of Health&Welfare,Republic of Korea(HI12C0014)Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2012R1A1A2006858)+1 种基金Chong Kun Dang Pharmaceutical Corp.,Seoul,Koreaapproved by the Institutional Review Board of Seoul National University Hospital(No.0911-027-300).
文摘Background:Cyclosporine A and tacrolimus(TAC)are often used as a second-line treatment for children with refractory nephrotic syndrome(NS).This study was undertaken to investigate the efficacy and safety of Tacrobell®,a locally produced generic form of TAC.Methods:This study was a one-year prospective,open-label,single-arm,multicenter trial.Fourty-four children with steroid-dependent NS(SDNS)and 33 children with steroid-resistant NS(SRNS)were enrolled.The primary endpoints were defined as the remission rates,whereas the secondary endpoints were recognized as the duration of remission and adverse effects of TAC.Results:After one-year treatment,34(77.3%)of the 44 patients with SDNS were in complete remission,and 6(13.6%)were in partial remission.Nineteen(43.2%)patients did not relapse during the study;for those who did relapse,the mean duration of remission was 4.6±2.9 months.The number of relapse episodes during the study period(0.90 per patient-year)was significantly lower than that in the preceding year(2.8 per patientyear).After treatment for 3 and 6 months,12(36.4%)of the 33 patients with SRNS were in remission,and after treatment for 12 months,the number of patients had increased to 13(39.4%).The mean time to achieve remission was 4.0±3.2 months.After remission(duration,3.7±2.7 months),12(54.5%)of 22 patients relapsed.The fasting blood glucose and blood pressure levels during the therapy were similar to those at the time of study entry.Conclusions:Treatment with Tacrobell®was effective and safe for children with refractory NS.The efficacy of this generic form of TAC was better than that of the original TAC formula.
