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[PMID]:27777266
[Au] Autor:De Vriese AS; Glassock RJ; Nath KA; Sethi S; Fervenza FC
[Ad] Endereço:Division of Nephrology, AZ Sint-Jan Brugge-Oostende, Brugge, Belgium; an.devriese@azsintjan.be fervenza.fernando@mayo.edu.
[Ti] Título:A Proposal for a Serology-Based Approach to Membranous Nephropathy.
[So] Source:J Am Soc Nephrol;28(2):421-430, 2017 Feb.
[Is] ISSN:1533-3450
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Primary membranous nephropathy (MN) is an autoimmune disease mainly caused by autoantibodies against the recently discovered podocyte antigens: the M-type phospholipase A2 receptor 1 (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A). Assays for quantitative assessment of anti-PLA2R antibodies are commercially available, but a semiquantitative test to detect anti-THSD7A antibodies has been only recently developed. The presence or absence of anti-PLA2R and anti-THSD7A antibodies adds important information to clinical and immunopathologic data in discriminating between primary and secondary MN. Levels of anti-PLA2R antibodies and possibly, anti-THSD7A antibodies tightly correlate with disease activity. Low baseline and decreasing anti-PLA2R antibody levels strongly predict spontaneous remission, thus favoring conservative therapy. Conversely, high baseline or increasing anti-PLA2R antibody levels associate with nephrotic syndrome and progressive loss of kidney function, thereby encouraging prompt initiation of immunosuppressive therapy. Serum anti-PLA2R antibody profiles reliably predict response to therapy, and levels at completion of therapy may forecast long-term outcome. Re-emergence of or increase in antibody titers precedes a clinical relapse. Persistence or reappearance of anti-PLA2R antibodies after kidney transplant predicts development of recurrent disease. We propose that an individualized serology-based approach to MN, used to complement and refine the traditional proteinuria-driven approach, will improve the outcome in this disease.
[Mh] Termos MeSH primário: Glomerulonefrite Membranosa/sangue
Glomerulonefrite Membranosa/diagnóstico
[Mh] Termos MeSH secundário: Algoritmos
Autoanticorpos/sangue
Glomerulonefrite Membranosa/terapia
Seres Humanos
Transplante de Rim
Prognóstico
Receptores da Fosfolipase A2/imunologia
Testes Sorológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Autoantibodies); 0 (PLA2R1 protein, human); 0 (Receptors, Phospholipase A2)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:180201
[Lr] Data última revisão:
180201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE
[do] DOI:10.1681/ASN.2016070776


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[PMID]:29202533
[Au] Autor:Xu J; Hu XF; Huang W; Shen PY; Zhang W; Ren H; Li X; Wang WM; Chen N; Pan XX
[Ad] Endereço:Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
[Ti] Título:[The clinicopathological characteristics of diabetic nephropathy and non-diabetic renal diseases in diabetic patients].
[So] Source:Zhonghua Nei Ke Za Zhi;56(12):924-929, 2017 Dec 01.
[Is] ISSN:0578-1426
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To analyze the clinicopathological characteristics of renal lesions in type 2 diabetic patients and to differentiate diabetic nephropathy (DN) from non-diabetic renal diseases(NDRD). Type 2 diabetic patients who received renal biopsy in Ruijin Hospital from January 2011 to December 2015 were recruited in this study. Clinical history, laboratory results and pathological data were retrospectively collected. According to the pathological findings, the patients were divided into 3 groups: DN, NDRD, DN+NDRD. Logistic model was applied to explore the independent clinical predictive factors in differentiating DN from NDRD. A total of 207 type 2 diabetic patients received renal biopsy, accounting for 6.82% of all biopsy population. Fifty-one patients were diagnosed with DN, 142 with NDRD and 14 with both DN and NDRD. In NDRD, membranous nephropathy(MN)(34.5%) was the most common finding, followed by IgA nephropathy(19.7%).By contrast, NDRD patients manifested a shorter diabetic course, a higher baseline hemoglobin level, a lower baseline serum creatinine, a higher prevalence of hematuria, a lower prevalence of hypertension and diabetic retinopathy, a better control of blood glucose, better compliance of monitoring blood glucose and less family history of diabetes. In multivariate logistic model, diabetic family history( 4.68, 0.04) and long history of diabetes( 1.01, 0.02) were risk factors of DN. There is a high prevalence of NDRD in diabetic patients with renal lesions. Family history of diabetes and duration of diabetes are independent predictors of DN.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/patologia
Nefropatias Diabéticas/patologia
Taxa de Filtração Glomerular/fisiologia
Nefropatias/patologia
Rim/patologia
[Mh] Termos MeSH secundário: Biópsia
China/epidemiologia
Diabetes Mellitus Tipo 2/complicações
Diabetes Mellitus Tipo 2/epidemiologia
Nefropatias Diabéticas/epidemiologia
Nefropatias Diabéticas/etiologia
Feminino
Glomerulonefrite por IGA/epidemiologia
Glomerulonefrite Membranosa/epidemiologia
Hematúria/epidemiologia
Seres Humanos
Hipertensão/epidemiologia
Rim/fisiopatologia
Nefropatias/epidemiologia
Nefropatias/etiologia
Modelos Logísticos
Masculino
Meia-Idade
Prevalência
Estudos Retrospectivos
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180111
[Lr] Data última revisão:
180111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0578-1426.2017.12.007


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[PMID]:28745685
[Au] Autor:Dobronravov VA; Mayer DA; Berezhnaya OV; Lapin SV; Mazing AV; Sipovsky VG; Smirnov AV
[Ad] Endereço:I.P. Pavlov First Saint Petersburg State Medical University, Ministry of Health of Russia, Saint Petersburg, Russia.
[Ti] Título:[Membranous nephropathy in a Russian population].
[Ti] Título:Membranoznaia nefropatiia v rossiiskoi populiatsii..
[So] Source:Ter Arkh;89(6):21-29, 2017.
[Is] ISSN:0040-3660
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:AIM: To analyze the clinical and morphological manifestations of membranous nephropathy (MN) and to evaluate the efficiency of its therapy. MATERIAL AND METHODS: MN cases in 2009 to 2016 were retrospectively detected with a subsequent analysis of patients with primary MN (PMN). The titer of IgG-autoantibodies to phospholipase A2 receptor (anti-PLA2R Ab) was determined by an indirect immunofluorescence assay. Treatment outcomes, such as the time course of changes in proteinuria, nephrotic syndrome (NS), and the development of complete and partial remissions (CR and PR), were assessed. RESULTS: MN was detected in 201 cases; the secondary etiology of the disease was established in 24.9%. The prevalence of MN among morphologically confirmed glomerulopathies was 14%; that of PMN was 10.4%. The median period to diagnosis PMN was 8 (5; 19) months. 150 patients with PMN (66.7% were men; age was 50±15 years) were distributed according to the following morphological stages: Stages I (23.9%), II (48.5%), III (26.1%), and IV (1.5%). Elevated anti-PLA2R Ab levels were found in 51.6% of cases; NS in the presence of proteinuria was detected in 85.6% of patients. An estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 was seen in 25% of cases. Treatment outcomes were evaluated in 80 cases; the median follow-up period was 19 (8; 40) months. 68% of cases had CR (32%) or PR (36%) with a median follow-up of 26 (13; 44) months. Spontaneous CRs or PRs were observed in 7.5% of the patients. Multivariate analysis showed that the probability of CR or PR increased 3.2-fold in the use of cyclophosphamide and/or cyclosporine and decreased as eGFR dropped. CONCLUSION: In Russia, PMN is a common type of glomerulopathy, the specific features of which should include the low rates of spontaneous remissions and detection of anti-PLA2R Abs. For renal protection, the majority of patients with PMN require timely diagnosis and treatment; individualization of the choice of treatment and its enhanced efficiency call for further investigations.
[Mh] Termos MeSH primário: Glomerulonefrite Membranosa/epidemiologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Glomerulonefrite Membranosa/sangue
Glomerulonefrite Membranosa/classificação
Glomerulonefrite Membranosa/etiologia
Seres Humanos
Masculino
Meia-Idade
Prevalência
Federação Russa/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171129
[Lr] Data última revisão:
171129
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.17116/terarkh201789621-29


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[PMID]:29068987
[Au] Autor:Chen R; Li F; Xie Q; Xue J; Lai L; Liu S; Zhang L; Hao C
[Ad] Endereço:aDivision of Nephrology, Huashan Hospital bDepartment of Pathology, Shanghai Medical College, Fudan University, Shanghai, China.
[Ti] Título:Membranous nephropathy in a patient with ankylosing spondylitis: A case report.
[So] Source:Medicine (Baltimore);96(43):e8201, 2017 Oct.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Renal complications in ankylosing spondylitis (AS) were rarely observed, and proteinuria associated with AS can be seen often due to amyloidosis in this kind of complications, while membranous nephropathy (MN) is seldom considered. This article reports a case of coexistence of AS and MN, to provide the exact relationship of these 2 entities and recognized some causes of renal involvement in AS. PATIENT CONCERNS: A 44-year-old female presented with pain of the left leg for 4 years and pedal edema for 2 weeks. DIAGNOSES: AS was diagnosed according to the patient's clinical manifestation and sacroiliitis observed on computed tomography (CT) scan. Nephrotic syndrome was found and MN was diagnosed according to kidney biopsy in which thickened capillary loops were observed with light microscopy, granular deposits of IgG along the capillary wall were observed using immunofluorescence staining, and subepithelial electron-dense deposits were observed with electron microscopy. No other secondary causes of MN were found on extensive investigations. INTERVENTION: Given the diagnoses, the patient received nonimmunosuppressive therapy for MN and adalimumab for AS. OUTCOMES: The patient got pain relief, as well as urinary protein reduction. LESSONS: This case suggested a secondary MN in association with AS and the relationship between these 2 diseases needed more concern and further illumination.
[Mh] Termos MeSH primário: Glomerulonefrite Membranosa/complicações
Espondilite Anquilosante/complicações
[Mh] Termos MeSH secundário: Adalimumab/uso terapêutico
Adulto
Celecoxib/uso terapêutico
Inibidores de Ciclo-Oxigenase 2/uso terapêutico
Feminino
Glomerulonefrite Membranosa/tratamento farmacológico
Glomerulonefrite Membranosa/etiologia
Glomerulonefrite Membranosa/patologia
Seres Humanos
Espondilite Anquilosante/tratamento farmacológico
Fator de Necrose Tumoral alfa/antagonistas & inibidores
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclooxygenase 2 Inhibitors); 0 (Tumor Necrosis Factor-alpha); FYS6T7F842 (Adalimumab); JCX84Q7J1L (Celecoxib)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171123
[Lr] Data última revisão:
171123
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171026
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008201


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[PMID]:28898290
[Au] Autor:Ren S; Wang Y; Xian L; Toyama T; Jardine M; Li G; Perkovic V; Hong D
[Ad] Endereço:Renal Division and Institute of Nephrology, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
[Ti] Título:Comparative effectiveness and tolerance of immunosuppressive treatments for idiopathic membranous nephropathy: A network meta-analysis.
[So] Source:PLoS One;12(9):e0184398, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Immunosuppressive agents in general are shown to prevent renal progression and all-cause mortality in idiopathic membranous nephropathy (IMN) patients with nephrotic syndrome. However, the efficacy and safety of different immunosuppressive treatments have not been systematic assessed and compared. A network meta-analysis was performed to compare different immunosuppressive treatment in IMN. METHODS: Cochrane library, MEDLINE, EMBASE and trial register system were searched for randomized controlled trials reporting the treatments for IMN to May 3, 2016. Composite endpoint of mortality or end-stage kidney disease (ESKD), complete or partial proteinuria remission and withdrawal because of treatment adverse events were compared combing direct and indirect comparison using network meta-analysis. Ranking different immunosuppressive treatments in the outcomes were analyzed by using surface under the cumulative ranking curve (SUCRA). RESULTS: Total 36 randomized controlled trials (n = 2018) covering 11 kinds of treatments were included. Compared with non-immunosuppressive treatment, only cyclophosphamide (CTX) and chlorambucil significantly reduced the risk of composite outcome of mortality or ESKD while combining the direct and indirect comparison (OR = 0.31, 95%CI: 0.12-0.81 and OR = 0.33, 95%CI: 0.12-0.92). CTX increased the composite outcome of complete remission (CR) or partial remission (PR) (OR = 4.29, 95%CI: 2.30-8.00) but chlorambucil did not (OR = 1.58, 95%CI: 0.80-3.12) as compared with non-immunosuppressive treatment. Chlorambucil also significantly increased the withdrawal risk (OR = 3.34, 95%CI: 1.37-8.17) as compared to CTX. Both tacrolimus (OR = 3.10, 95%CI: 1.36-7.09) and cyclosporine (CsA) (OR = 2.81, 95%CI: 1.08-7.32) also significantly increased the rate of CR or PR as compared with non-immunosuppressive treatment (without significant difference as compared with CTX), while ranking results showed that cyclosporine or tacrolimus was with less possibility of drug withdrawal as compared to CTX. CONCLUSIONS: Cyclophosphamide and chlorambucil reduce risk of ESKD or death in IMN with nephrotic range proteinuria, but carry substantial toxicity that may be lower for cyclophosphamide. Tacrolimus and cyclosporine increase the possibility of proteinuria remission with less drug withdrawal, but the effects on kidney failure remain uncertain.
[Mh] Termos MeSH primário: Clorambucila/efeitos adversos
Ciclofosfamida/efeitos adversos
Ciclosporina/efeitos adversos
Glomerulonefrite Membranosa/tratamento farmacológico
Imunossupressores/efeitos adversos
Tacrolimo/efeitos adversos
[Mh] Termos MeSH secundário: Clorambucila/administração & dosagem
Clorambucila/uso terapêutico
Ciclofosfamida/administração & dosagem
Ciclofosfamida/uso terapêutico
Ciclosporina/administração & dosagem
Ciclosporina/uso terapêutico
Tolerância a Medicamentos
Feminino
Seres Humanos
Imunossupressores/administração & dosagem
Imunossupressores/uso terapêutico
Masculino
Ensaios Clínicos Controlados Aleatórios como Assunto
Tacrolimo/administração & dosagem
Tacrolimo/uso terapêutico
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; META-ANALYSIS
[Nm] Nome de substância:
0 (Immunosuppressive Agents); 18D0SL7309 (Chlorambucil); 83HN0GTJ6D (Cyclosporine); 8N3DW7272P (Cyclophosphamide); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184398


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[PMID]:28814510
[Au] Autor:Tomas NM; Meyer-Schwesinger C; von Spiegel H; Kotb AM; Zahner G; Hoxha E; Helmchen U; Endlich N; Koch-Nolte F; Stahl RAK
[Ad] Endereço:III. Medizinische Klinik, n.tomas@uke.de.
[Ti] Título:A Heterologous Model of Thrombospondin Type 1 Domain-Containing 7A-Associated Membranous Nephropathy.
[So] Source:J Am Soc Nephrol;28(11):3262-3277, 2017 Nov.
[Is] ISSN:1533-3450
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Thrombospondin type 1 domain-containing 7A (THSD7A) is a target for autoimmunity in patients with membranous nephropathy (MN). Circulating autoantibodies from patients with THSD7A-associated MN have been demonstrated to cause MN in mice. However, THSD7A-associated MN is a rare disease, preventing the use of patient antibodies for larger experimental procedures. Therefore, we generated antibodies against the human and mouse orthologs of THSD7A in rabbits by coimmunization with the respective cDNAs. Injection of these anti-THSD7A antibodies into mice induced a severe nephrotic syndrome with proteinuria, weight gain, and hyperlipidemia. Immunofluorescence analyses revealed granular antigen-antibody complexes in a subepithelial location along the glomerular filtration barrier 14 days after antibody injection, and immunohistochemistry for rabbit IgG and THSD7A as well as ultrastructural analyses showed the typical characteristics of human MN. Mice injected with purified IgG from rabbit serum that was taken before immunization failed to develop any of these changes. Notably, MN developed in the absence of detectable complement activation, and disease was strain dependent. , anti-THSD7A antibodies caused cytoskeletal rearrangement and activation of focal adhesion signaling. Knockdown of the THSD7A ortholog, thsd7aa, in zebrafish larvae resulted in altered podocyte differentiation and impaired glomerular filtration barrier function, with development of pericardial edema, suggesting an important role of THSD7A in glomerular filtration barrier integrity. In summary, our study introduces a heterologous mouse model that allows further investigation of the molecular events that underlie MN.
[Mh] Termos MeSH primário: Anticorpos/fisiologia
Antígenos de Superfície/imunologia
Glomerulonefrite Membranosa/imunologia
Proteínas de Membrana/imunologia
Trombospondinas/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos de Superfície/fisiologia
Modelos Animais de Doenças
Seres Humanos
Masculino
Proteínas de Membrana/fisiologia
Camundongos
Camundongos Endogâmicos BALB C
Coelhos
Ratos
Ratos Sprague-Dawley
Trombospondinas/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (Antigens, Surface); 0 (Membrane Proteins); 0 (Thrombospondins); 0 (Thsd7A protein, mouse); 0 (thrombospondin type I domain containing 7A protein, human)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1681/ASN.2017010030


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[PMID]:28711658
[Au] Autor:Sutariya B; Taneja N; Saraf M
[Ad] Endereço:Department of Pharmacology, Bombay College of Pharmacy, Kalina, Santacruz (East), Mumbai, 400068, Maharashtra, India.
[Ti] Título:Betulinic acid, isolated from the leaves of Syzygium cumini (L.) Skeels, ameliorates the proteinuria in experimental membranous nephropathy through regulating Nrf2/NF-κB pathways.
[So] Source:Chem Biol Interact;274:124-137, 2017 Aug 25.
[Is] ISSN:1872-7786
[Cp] País de publicação:Ireland
[La] Idioma:eng
[Ab] Resumo:Membranous nephropathy (MN) is associated with increased oxidative stress and inflammatory markers in the kidney. Betulinic acid (BA) is a potent antioxidant and anti-inflammatory compound isolated from the leaves of Syzygium cumini (L.) Skeels. In the present study, we investigated the effects of BA on experimental MN in rats and explored the mechanisms by which it enhances antioxidant activities and resolves inflammatory condition in experimental MN. Passive Heymann nephritis (PHN) was induced in Sprague-Dawley rats by a single tail vein injection of anti- Fx1A antiserum. The rats were orally administered BA (25 and 50 mg kg  d ) or dexamethasone (DEX; 0.07 mg kg-1, reference compound) for 4 weeks after the induction of PHN. Blood, urine, and kidney tissue were collected for analysis at the end of the study. Treatment of PHN rats with BA or DEX significantly attenuated renal dysfunction, histopathological alterations and reduced immune complex deposition in the kidneys. Furthermore, BA ameliorated mRNA and protein expression of NF-κB, iNOS, TNF-α, Nrf2, HO-1 and NQO1 in the kidney. BA also restored malondialdehyde level and antioxidant enzyme activities in the kidney. In a nutshell, the protective effect of BA can be explained by its anti-inflammatory and anti-oxidant activities, which in turn is due to downregulation of NF-κB pathway and activation of Nrf2. The results indicated that BA can effectively suppress experimental PHN in rats by regulating Nrf2/NF-κB pathways.
[Mh] Termos MeSH primário: Glomerulonefrite Membranosa/prevenção & controle
Proteinúria/prevenção & controle
Transdução de Sinais/efeitos dos fármacos
Syzygium/química
Triterpenos/farmacologia
[Mh] Termos MeSH secundário: Animais
Anticorpos/administração & dosagem
Anticorpos/imunologia
Antioxidantes/metabolismo
Dexametasona/farmacologia
Feminino
Glomerulonefrite Membranosa/patologia
Complexo Antigênico da Nefrite de Heymann/imunologia
Rim/efeitos dos fármacos
Rim/metabolismo
Rim/patologia
Peroxidação de Lipídeos/efeitos dos fármacos
Masculino
Malondialdeído/sangue
Fator 2 Relacionado a NF-E2/genética
Fator 2 Relacionado a NF-E2/metabolismo
NF-kappa B/genética
NF-kappa B/metabolismo
Folhas de Planta/química
Folhas de Planta/metabolismo
Coelhos
Ratos
Ratos Sprague-Dawley
Syzygium/metabolismo
Triterpenos/química
Triterpenos/isolamento & purificação
Triterpenos/uso terapêutico
Fator de Necrose Tumoral alfa/genética
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (Antioxidants); 0 (Heymann Nephritis Antigenic Complex); 0 (NF-E2-Related Factor 2); 0 (NF-kappa B); 0 (Triterpenes); 0 (Tumor Necrosis Factor-alpha); 4G6A18707N (betulinic acid); 4Y8F71G49Q (Malondialdehyde); 7S5I7G3JQL (Dexamethasone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170717
[St] Status:MEDLINE


  8 / 2733 MEDLINE  
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[PMID]:28674044
[Au] Autor:Beck LH
[Ad] Endereço:Renal Section, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts Laurence.Beck@bmc.org lhbeckjr@bu.edu.
[Ti] Título:PLA2R and THSD7A: Disparate Paths to the Same Disease?
[So] Source:J Am Soc Nephrol;28(9):2579-2589, 2017 Sep.
[Is] ISSN:1533-3450
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major autoantigens in primary membranous nephropathy (MN), and define two molecular subclasses of this disease. Both proteins are large transmembrane glycoproteins expressed by the podocyte, and both induce IgG4-predominant humoral immune responses that produce circulating autoantibodies that can be used clinically for diagnostic and monitoring purposes. The biologic roles of these proteins remain speculative, although several features of THSD7A suggest a role in adhesion. PLA2R-associated MN was initially found to associate with risk alleles within , but subsequent studies have shifted the focus to the HLA-DRB locus. Three distinct humoral epitope-containing regions have been defined within the extracellular portion of PLA2R, and it appears that the number of targeted epitopes may determine disease severity. Although similar information is not yet available for THSD7A-associated MN, this form of MN may have a unique association with malignancy. Finally, it appears likely that other autoantigens in primary MN exist. Although protocols similar to those that identified PLA2R and THSD7A may be successful in the identification of novel antigenic targets in MN, newer techniques such as laser-capture mass spectrometry or protein arrays may be helpful as well.
[Mh] Termos MeSH primário: Autoantígenos/imunologia
Glomerulonefrite Membranosa/imunologia
Neoplasias/imunologia
Receptores da Fosfolipase A2/genética
Receptores da Fosfolipase A2/imunologia
Trombospondinas/imunologia
[Mh] Termos MeSH secundário: Autoanticorpos
Autoantígenos/genética
Epitopos/genética
Cadeias alfa de HLA-DQ/genética
Cadeias beta de HLA-DR/genética
Seres Humanos
Imunoglobulina G
Podócitos/metabolismo
Receptores da Fosfolipase A2/isolamento & purificação
Receptores da Fosfolipase A2/metabolismo
Trombospondinas/isolamento & purificação
Trombospondinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Autoantigens); 0 (Epitopes); 0 (HLA-DQ alpha-Chains); 0 (HLA-DQA1 antigen); 0 (HLA-DR beta-Chains); 0 (Immunoglobulin G); 0 (Receptors, Phospholipase A2); 0 (Thrombospondins); 0 (thrombospondin type I domain containing 7A protein, human)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE
[do] DOI:10.1681/ASN.2017020178


  9 / 2733 MEDLINE  
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[PMID]:28669992
[Au] Autor:Ruggenenti P; Fervenza FC; Remuzzi G
[Ad] Endereço:IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Via Stezzano 87, 24126 Bergamo, Italy.
[Ti] Título:Treatment of membranous nephropathy: time for a paradigm shift.
[So] Source:Nat Rev Nephrol;13(9):563-579, 2017 Sep.
[Is] ISSN:1759-507X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In patients with membranous nephropathy, alkylating agents (cyclophosphamide or chlorambucil) alone or in combination with steroids achieve remission of nephrotic syndrome more effectively than conservative treatment or steroids alone, but can cause myelotoxicity, infections, and cancer. Calcineurin inhibitors can improve proteinuria, but are nephrotoxic. Most patients relapse after treatment withdrawal and can become treatment dependent, which increases the risk of nephrotoxicity. The discovery of nephritogenic autoantibodies against podocyte M-type phospholipase A2 receptor (PLA R) and thrombospondin type-1 domain- containing protein 7A (THSD7A) antigens provides a clear pathophysiological rationale for interventions that specifically target B-cell lineages to prevent antibody production and subepithelial deposition. The anti-CD20 monoclonal antibody rituximab is safe and achieves remission of proteinuria in approximately two-thirds of patients with membranous nephropathy. In those with PLA R-related disease, remission can be predicted by anti-PLA R antibody depletion and relapse by antibody re-emergence into the circulation. Thus, integrated evaluation of serology and proteinuria could guide identification of affected patients and treatment with individually tailored protocols. Nonspecific and toxic immunosuppressive regimens will fall out of use. B-cell modulation by rituximab and second-generation anti-CD20 antibodies (or plasma cell-targeted therapy in anti-CD20 resistant forms of disease) will lead to a novel therapeutic paradigm for patients with membranous nephropathy.
[Mh] Termos MeSH primário: Glomerulonefrite Membranosa/terapia
[Mh] Termos MeSH secundário: Linfócitos B
Ensaios Clínicos como Assunto
Ciclofosfamida/uso terapêutico
Seres Humanos
Fatores Imunológicos/uso terapêutico
Imunossupressão
Imunossupressores/uso terapêutico
Procedimentos de Redução de Leucócitos
Rituximab/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Immunologic Factors); 0 (Immunosuppressive Agents); 4F4X42SYQ6 (Rituximab); 8N3DW7272P (Cyclophosphamide)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170704
[St] Status:MEDLINE
[do] DOI:10.1038/nrneph.2017.92


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[PMID]:28614271
[Au] Autor:Pang L; Zhang AM; Li HX; Du JL; Jiao LL; Duan N; Liu Y; Yu D
[Ad] Endereço:aDepartment of Clinical Laboratory, Peking University First Hospital, Beijing bDepartment of Clinical Laboratory, Tianjin Nankai Hospital, Tianjin, The People's Republic of China.
[Ti] Título:Serum anti-PLA2R antibody and glomerular PLA2R deposition in Chinese patients with membranous nephropathy: A cross-sectional study.
[So] Source:Medicine (Baltimore);96(24):e7218, 2017 Jun.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:M-type phospholipase A2 receptor (PLA2R) is the major target antigen in primary membranous nephropathy (PMN). Previous studies have evaluated the diagnostic value of serum anti-PLA2R antibody. However, the correlation of serum anti-PLA2R antibody and glomerular PLA2R deposition, and their association with clinical characteristics need to be further evaluated.A total of 136 patients were involved as inception group because serum anti-PLA2R antibody and glomerular PLA2R antigen were simultaneously measured. We examined serum anti-PLA2R antibody by ELISA and glomerular PLA2R deposition by immunofluorescence assay.Positive serum anti-PLA2R antibody and glomerular PLA2R deposition were seen in 58.8% (80/136) and 95.6% (130/136) patients, respectively (P < .001). Proteinuria, serum total protein, serum albumin, serum creatinine, and estimated glomerular filtration rate (eGFR) had significant differences between patients with serum anti-PLA2R antibody and those without. Serum anti-PLA2R antibody levels were correlated with serum albumin, serum creatinine, eGFR, and proteinuria. Glomerular PLA2R deposition intensities were weakly correlated with proteinuria. Unexpectedly, there was a positive correlation rather than a negative correlation between glomerular PLA2R deposition intensity and eGFR.In conclusion, serum anti-PLA2R antibody is more closely correlated with disease activity and renal function than glomerular PLA2R deposition.
[Mh] Termos MeSH primário: Autoanticorpos/sangue
Glomerulonefrite Membranosa/metabolismo
Imunoglobulina G/metabolismo
Rim/metabolismo
Receptores da Fosfolipase A2/metabolismo
[Mh] Termos MeSH secundário: Biomarcadores/metabolismo
China
Creatinina/sangue
Estudos Transversais
Ensaio de Imunoadsorção Enzimática
Imunofluorescência
Taxa de Filtração Glomerular
Glomerulonefrite Membranosa/tratamento farmacológico
Glomerulonefrite Membranosa/patologia
Seres Humanos
Rim/patologia
Proteinúria/tratamento farmacológico
Proteinúria/metabolismo
Proteinúria/patologia
Estudos Retrospectivos
Sensibilidade e Especificidade
Albumina Sérica/análise
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Biomarkers); 0 (Immunoglobulin G); 0 (PLA2R1 protein, human); 0 (Receptors, Phospholipase A2); 0 (Serum Albumin); AYI8EX34EU (Creatinine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170615
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007218



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