RESUMO
OBJECTIVE: High serum levels of B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL) have been observed in patients with idiopathic membranous nephropathy (iMN); however, their relationships with disease severity and progression remain unclear. METHODS: Patients with iMN diagnosed via renal biopsy were enrolled in this study. The concentrations of BAFF and APRIL were determined using ELISA kits. Proteinuria remission, including complete remission (CR) and partial remission (PR), and renal function deterioration were defined as clinical events. The Cox proportional hazards method was used to analyze the relationship between cytokine levels and disease progression. RESULTS: Seventy iMN patients were enrolled in this study, with a median follow-up time of 24 months (range 6-72 months). The serum levels of BAFF and APRIL were higher in iMN patients than in healthy controls but lower than those in minimal change disease (MCD) patients. The serum BAFF level was positively correlated with the serum APRIL level, serum anti-phospholipase A2 receptor (anti-PLA2R) antibody level, and 24-h proteinuria and negatively correlated with the serum albumin (ALB) level. However, no significant correlation was observed between the serum APRIL level and clinical parameters. According to the multivariate Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure (SBP), estimated glomerular filtration rate (eGFR), immunosuppressive agent use, 24-h proteinuria, APRIL level, and anti-PLA2R antibody, only the serum BAFF level was identified as an independent predictor of PR (HR, 0.613; 95% CI, 0.405-0.927; p = 0.021) and CR of proteinuria (HR, 0.362; 95% CI, 0.202-0.648; p < 0.001). CONCLUSIONS: A high serum BAFF level is associated with severe clinical manifestations and poor disease progression in patients with iMN.
Assuntos
Fator Ativador de Células B , Progressão da Doença , Glomerulonefrite Membranosa , Proteinúria , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Humanos , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/diagnóstico , Fator Ativador de Células B/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Prognóstico , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Proteinúria/sangue , Proteinúria/etiologia , Modelos de Riscos Proporcionais , Receptores da Fosfolipase A2/imunologia , Receptores da Fosfolipase A2/sangue , Estudos de Casos e Controles , Idoso , Taxa de Filtração Glomerular , Rim/fisiopatologia , Rim/patologiaRESUMO
Patients with nephrotic syndrome (NS) present with edema, proteinuria, hypoalbuminemia, and hyperlipidemia. In children, the most common causes are idiopathic minimal change disease and focal segmental glomerulosclerosis (FSGS). In adults, FSGS and membranous nephropathy (MN) are the most common primary causes. There are numerous secondary causes, including diabetes, amyloidosis, systemic lupus erythematosus, hematologic malignancies, and infections. In addition to confirming the diagnosis of NS by measuring proteinuria and serum albumin and lipid levels, evaluation should assess for secondary causes. In children, most cases are due to minimal change disease, which is responsive to steroid treatment. A glucocorticoid should be prescribed for children younger than 12 years. If the patient improves with steroid treatment, no biopsy is needed. If the patient does not improve, genetic testing and kidney biopsy are warranted to determine the diagnosis. In adults, biopsy typically is indicated for diagnosis, except in patients with positive test results for serum anti-phospholipase A2 receptor antibodies. This is diagnostic of MN. For patients with NS, management of initial and infrequent recurrences involves reduction of proteinuria with glucocorticoids. Frequent recurrences and/or the inability to discontinue glucocorticoids requires alternative therapies. Steroid-resistant NS also requires use of alternative therapies. Long-term NS management includes dietary sodium restriction, edema management, and blood pressure control. Thromboembolism prophylaxis should be considered for patients with NS and high risk of thromboembolism, particularly those with MN.
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Síndrome Nefrótica , Humanos , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/terapia , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/terapia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/terapia , Glucocorticoides/uso terapêutico , Adulto , Criança , Nefrose Lipoide/diagnóstico , Nefrose Lipoide/terapia , Proteinúria/diagnóstico , Proteinúria/etiologiaRESUMO
AIM: To evaluate the clinical and pathological features and prognosis of idiopathic membranous nephropathy (IMN) with focal segmental sclerosis (FSGS) in a group of Russian patients. MATERIALS AND METHODS: 101 patients with morphologically verified IMN were enrolled in our single-center cohort retrospective study. The patients were divided into IMN group and IMN+FSGS group. The primary and secondary outcomes were analyzed in 59 patients, which had follow-up data for period more than 6 months. RESULTS: At the time of renal biopsy the median age was 46.0 (33.0; 55.0) years and the median follow-up was 6.8 (4.0; 15.6) months. Secondary FSGS was revealed in 15 (14.9%) patients with IMN. The IMN and IMN+FSGS groups did not differ in gender, age of onset IMN and age of renal biopsy. In the IMN+FSGS group proteinuria was higher and estimated glomerular filtration rate was lower than that in the IMN group (p<0.05). The systolic arterial pressure and creatinine levels in the IMN+FSGS group were slightly higher than in the IMN group, but the difference was not significant. Anti-PLA2R positivity was similar in both groups. Chronic kidney disease (CKD) progression was observed in 10/52 (19.2%) and 5/7 (71.4%) patients in IMN and IMN+FSGS groups, respectively. In a multivariate Cox regression model, age of renal biopsy (odds ratio - OR 1.12, 95% confidence interval - CI 1.03-1.22; Ñ=0.07), FSGS (OR 0.05, 95% CI 0.01-0.34; Ñ=0.002) и response to initial course of immunosuppression (OR 0.33, 95% CI 0.12-0.95; Ñ=0.039) were associated with the CKD progression. CONCLUSION: In patients with IMN secondary FSGS is associated with a greater severity of proteinuria and a decrease in estimated glomerular filtration rate, and is also an independent factor of the CKD progression.
Assuntos
Taxa de Filtração Glomerular , Glomerulonefrite Membranosa , Glomerulosclerose Segmentar e Focal , Humanos , Masculino , Glomerulonefrite Membranosa/fisiopatologia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Feminino , Pessoa de Meia-Idade , Glomerulosclerose Segmentar e Focal/fisiopatologia , Glomerulosclerose Segmentar e Focal/diagnóstico , Adulto , Estudos Retrospectivos , Prognóstico , Progressão da Doença , Federação Russa/epidemiologia , Rim/patologia , Rim/fisiopatologia , Biópsia , Proteinúria/etiologia , Proteinúria/diagnóstico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologiaRESUMO
BACKGROUND: Nephrotic syndrome (NS) is a rare complication that can occur after haematopoietic stem cell transplantation (HSCT). In patients with membranous nephropathy (MN) who have undergone allogeneic HSCT, a new antigen called protocadherin FAT1 has been identified. Our objective is to present a case series of MN patients after HSCT with a novel antigen-based stratification. CASE PRESENTATIONS: Patients who developed full-blown NS due to MN after an HSCT were enrolled in the University Hospital Centre Zagreb study. The first two patients were treated with an HSCT for acute myeloid leukaemia, and both developed NS after cessation of graft versus host disease (GVHD) prophylaxis. The first patient had reduced kidney function, while the second had completely preserved function. Kidney biopsy showed MN with only subepithelial deposits. A thorough examination revealed that there was no secondary cause of the disease. The patients achieved complete remission after undergoing immunosuppression treatment. The third patient underwent HSCT for acute lymphoblastic leukaemia. He developed both acute and chronic GVHD and also experienced avascular hip necrosis. After sixteen years, the patient developed NS with preserved kidney function. The kidney specimen showed membranous nephropathy (MN) with mesangial and subepithelial deposits. Extensive research was conducted, but no secondary cause for the MN was detected. All three cases tested negative for anti-PLA2R antibodies. Biopsy tissue samples were analysed using laser microdissection and tandem mass spectrometry of glomeruli for the detection of different specific antigens. Patients one and two tested positive for FAT1, whereas patient three tested positive for PCSK6. CONCLUSIONS: MN can develop at various time intervals after HSCT. Specific antigen testing can help establish the relationship between MN and HSCT. In the future, serum testing for anti-FAT1 antibodies in HSCT patients could be significant in diagnosing FAT1-associated MN, similar to how anti-PLA2R antibodies are significant in diagnosing PLA2R-associated MN.
Assuntos
Glomerulonefrite Membranosa , Transplante de Células-Tronco Hematopoéticas , Humanos , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Adulto , Pessoa de Meia-Idade , Leucemia Mieloide Aguda/terapia , Síndrome Nefrótica/etiologiaRESUMO
Objective: To investigate the clinicopathological features of renal leukocyte chemokine type 2 amyloidosis (ALECT2). Methods: The prevalence, clinical characteristics, renal histopathological features, and renal outcome of 15 patients with ALECT2 by kidney biopsy were collected in the Department of Kidney Pathology, Shanxi Medical University Second Hospital, Taiyuan, China from January 1993 to December 2023. Immunohistochemistry and mass spectrometry for amyloid proteins were carried out. Results: Fifteen patients with ALECT2 were included in the study, representing 12.93% (15/116) of the renal biopsy-proven amyloidosis cases. There were 5 males and 10 females. The median age at diagnosis was 61 years. All patients had various degrees of proteinuria; 7 patients had nephrotic syndrome; 3 patients had renal insufficiency; 7 patients had microscopic hematuria. Renal biopsy showed that strongly orangophilic amyloid proteins distributed mainly in the renal cortical interstitium, vascular walls, the glomerular mesangium and/or glomerular basement membrane. Eight cases were diagnosed with ALECT2 alone and 7 cases combined with other renal diseases, including 4 cases with membranous nephropathy, 2 cases with IgA nephropathy, and 1 case with subacute tubular interstitial nephropathy. ALECT2 patients with concurrent renal disease showed a higher proteinuria level than those without (3.48 g/24 h versus 4.58 g/24 h). All patients were corroborated by immunohistochemistry to exhibit the specific location of LECT2 in the amyloid fibrils. Mass spectrometry analysis revealed LECT2 polypeptide in 9 patients. Except two patients with worsening renal function, the others showed stable renal function during the mean follow-up period of 12.5 months. Conclusions: ALECT2 is the second common type of renal amyloidosis in our center. The majority of ALECT2 patients show concurrent renal diseases, with a high rate of membranous nephropathy. Amyloid deposits distribute mainly in the cortical interstitium of the kidney, the glomerular mesangium and vascular walls. Mass spectrometry is the most sensitive and specific method for detecting LECT2 amyloidosis.
Assuntos
Amiloidose , Nefropatias , Rim , Síndrome Nefrótica , Humanos , Masculino , Amiloidose/metabolismo , Amiloidose/patologia , Amiloidose/diagnóstico , Feminino , Pessoa de Meia-Idade , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/patologia , Rim/patologia , Nefropatias/patologia , Nefropatias/metabolismo , Proteinúria , Biópsia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/metabolismo , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/metabolismo , Idoso , Hematúria/etiologia , Insuficiência Renal/metabolismoRESUMO
Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in adults and is associated with high rates of end-stage renal disease. Early detection and precise interventions are crucial for improving patient prognosis and quality of life. However, the current diagnosis primarily relies on renal biopsies and traditional biomarkers, which have limitations. Additionally, targeted therapeutic strategies are lacking. Exosomes, small vesicles that facilitate intercellular communication, have emerged as potential noninvasive diagnostic markers due to their stability, diverse cargo, and rapid detectability. They also hold promise as carriers for gene and drug delivery, presenting innovative opportunities in renal disease prognosis and treatment. However, research on exosomes in the context of idiopathic membranous nephropathy (IMN) remains limited, with a focus on exploring urinary exosomes as IMN markers. In this review, we summarize the current status of MN diagnosis and treatment, highlight the fundamental characteristics of exosomes, and discuss recent advancements in their application to IMN diagnosis and therapy. We provide insights into the clinical prospects of exosomes in IMN and acknowledge potential challenges. This article aims to offer forward-looking insights into the future of exosome-mediated IMN diagnosis and treatment, indicating a revolutionary transformation in this field.
Assuntos
Biomarcadores , Exossomos , Glomerulonefrite Membranosa , Exossomos/metabolismo , Glomerulonefrite Membranosa/diagnóstico , Humanos , Animais , PrognósticoRESUMO
Primary glomerular disease (PGD) is an idiopathic cause of renal glomerular lesions that is characterized by proteinuria or hematuria and is the leading cause of chronic kidney disease (CKD). The identification of circulating biomarkers for the diagnosis of PGD requires a thorough understanding of the metabolic defects involved. In this study, ultra-high performance liquid chromatography-tandem mass spectrometry was performed to characterize the amino acid (AA) profiles of patients with pathologically diagnosed PGD, including minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), membranous nephropathy, and immunoglobulin A nephropathy. The plasma concentrations of asparagine and ornithine were low, and that of aspartic acid was high, in patients with all the pathologic types of PGD, compared to healthy controls. Two distinct diagnostic models were generated using the differential plasma AA profiles using logistic regression and receiver operating characteristic analyses, with areas under the curves of 1.000 and accuracies up to 100.0% in patients with MCD and FSGS. In conclusion, the progression of PGD is associated with alterations in AA profiles, The present findings provide a theoretical basis for the use of AAs as a non-invasive, real-time, rapid, and simple biomarker for the diagnosis of various pathologic types of PGD.
Assuntos
Aminoácidos , Biomarcadores , Metabolômica , Humanos , Feminino , Masculino , Aminoácidos/sangue , Adulto , Metabolômica/métodos , Pessoa de Meia-Idade , Biomarcadores/sangue , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/diagnóstico , Nefrose Lipoide/sangue , Nefrose Lipoide/diagnóstico , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/diagnóstico , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/diagnóstico , Glomérulos Renais/metabolismo , Glomérulos Renais/patologiaRESUMO
Primary membranous nephropathy (PMN) is a predominant cause of adult nephrotic syndrome, with its incidence witnessing a progressive surge over time. Approximately 35% to 47% of patients progress to renal failure within 10 years, causing a huge social burden. Within China, the proportion of PMN in primary glomerular disease exhibits a gradual ascension. Recent studies have shown that the 3 activation pathways of complement: the classical pathway, mannose-binding lectin pathway, and alternative pathway, are all involved in the pathogenesis of PMN. Despite historical limitations in detecting C1q deposits on the glomeruli of PMN in the past, recent studies have confirmed the classical pathway is implicated in patients with PMN. Considering the dysregulation of the complement system has been observed in PMN, complement inhibitors become increasingly promising. Several clinical trials are presently underway to evaluate the efficacy of complement inhibitors, such as MASP2 antagonists (OMS721), C3 and C3b antagonists (APL2), FD inhibitors (BCX9930), C3aR antagonists (SB290157 and JR14a), FB inhibitors (LNP023). This article reviews the recent research progress on the role of the complement pathway in the pathogenesis of PMN, and underscores the importance of continued research into the complement pathway and its inhibitors, which may pave the way for groundbreaking advancements in the management of PMN.
Assuntos
Glomerulonefrite Membranosa , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Proteínas do Sistema Complemento , Inativadores do Complemento/uso terapêutico , Ativação do Complemento , Via Alternativa do Complemento/efeitos dos fármacosRESUMO
The progression and pathogenesis of membranous glomerulonephritis (MGN) are inextricably linked to chronic inflammation. Despite improving clinical remission rates due to the application of cyclophosphamide (CYC), treatment of MGN still requires further exploration. Ruxolitinib (Ruxo) negatively affects the signaling pathways participating in the production of pro-inflammatory cytokines. Hence, we investigated whether the combination of CYC and Ruxo can modulate inflammation through influencing T helper 17 (Th17) lineages and regulatory T cells (Tregs). Passive Heymann nephritis (PHN), an experimental model of MGN, was induced in a population of rats. Then, the animals were divided into five groups: PHN, CYC-receiving, Ruxo-receiving, CYC-Ruxo-receiving PHN rats, and healthy controls. After 28 days of treatment, biochemistry analysis was performed and splenocytes were isolated for flowcytometry investigation of Th17 cells and Tregs. The correlative transcription factors of the cells, alongside their downstream cytokine gene expressions, were also assessed using real-time PCR. Furthermore, serum cytokine signatures for the lymphocytes were determined through ELISA. The combination of CYC and Ruxo significantly reduced the serum values of urea in rats versus the PHN group (24.62 ± 7.970 vs. 40.60 ± 10.81 mg/dL). In contrast to Treg's activities, the functionality of Th17 cells noticeably increased not only in PHN rats but also in CYC or Ruxo-receiving PHN animals when compared with the control (10.60 ± 2.236, 8.800 ± 1.465, 8.680 ± 1.314 vs. 4.420 ± 1.551 %). However, in comparison to the PHN group, the incidence of Th17 cells notably fell in rats receiving CYC and Ruxo (10.60 ± 2.236 vs. 6.000 ± 1.373 %) in favor of the Treg's percentage (5.020 ± 1.761 vs. 8.980 ± 1.178 %), which was verified by the gene expressions and cytokine productions correlative to these lymphocytes. The combination of CYC and Ruxo was able to decline Th17 cells in favor of Tregs improvement in PHN rats, suggesting an innovative combination therapy in MGN treatment approaches.
Assuntos
Ciclofosfamida , Citocinas , Glomerulonefrite Membranosa , Nitrilas , Pirazóis , Pirimidinas , Linfócitos T Reguladores , Células Th17 , Animais , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Ratos , Pirazóis/farmacologia , Pirazóis/uso terapêutico , Citocinas/metabolismo , Masculino , Modelos Animais de Doenças , Quimioterapia CombinadaRESUMO
BACKGROUND: Nephrotic syndrome (NS) can occur as a paraneoplastic disorder in association with various types of carcinoma. However, paraneoplastic nephrotic syndrome (PNS) is often misdiagnosed as idiopathic nephrotic syndrome or as an adverse effect of oncology treatment, leading to delayed diagnosis and suboptimal treatment. The characteristics of NS associated with solid malignancies are not yet elucidated. We systematically summarized the clinical data for 128 cases of NS combined with solid malignancies with the aim of informing the clinical management of PNS. METHODS: We searched the PubMed database for articles published from the date of inception through to October 2023 using the following keywords: "cancer" or "malignant neoplasms" or "neoplasia" or "tumors" and "nephrotic syndrome", "nephrotic" or "syndrome, nephrotic". All data were extracted from case reports and case series, and the extraction included a method for identifying individual-level patient data. RESULTS: A literature search yielded 105 cases of PNS and 23 of NS induced by cancer therapy. The median age at diagnosis was 60 years, with a male to female ratio of 1.8:1. In patients with PNS, manifestations of NS occurred before, concomitantly with, or after diagnosis of the tumor (in 36%, 30%, and 34% of cases, respectively). Membranous nephropathy (49%) was the most prevalent renal pathology and found particularly in patients with lung, colorectal, or breast carcinoma. Regardless of whether treatment was for cancer alone or in combination with NS, the likelihood of remission was high. CONCLUSION: The pathological type of NS may be associated with specific malignancies in patients with PNS. Prompt identification of PNS coupled with suitable therapeutic intervention has a significant impact on the outcome for patients.
Assuntos
Neoplasias , Síndrome Nefrótica , Síndromes Paraneoplásicas , Humanos , Síndrome Nefrótica/complicações , Síndrome Nefrótica/etiologia , Neoplasias/complicações , Glomerulonefrite Membranosa/complicaçõesRESUMO
BACKGROUND: Patients with idiopathic membranous nephropathy (IMN) are more likely to be complicated by venous thromboembolism (VTE). The aim of the study was to investigate the potential association between anti-phospholipase A2 receptor (PLA2R) antibodies and hypercoagulability in patients with IMN. METHODS: A total of 168 patients with biopsy-proven IMN and 36 patients with biopsy-proven minimal change disease (MCD) were enrolled in this study. The clinical data, serum anti-PLA2R antibodies and coagulation-related indices of the patients were retrospectively analyzed. RESULTS: Patients with IMN were categorized into glomerular PLA2R staining-positive (GAg+) IMN group and glomerular PLA2R staining-negative (GAg-) IMN group in the study. Patients with IMN who were GAg + had lower PT, APTT and R time than patients with IMN who were GAg-, while the CI value was higher in patients with IMN who were GAg+. Patients with IMN who were GAg + were divided into the SAb+/GAg + group and the SAb-/GAg + group. Patients with IMN who were SAb+/GAg + had higher Fib and MA values than patients with IMN who were SAb-/GAg+. Correlation analysis showed that serum anti-PLA2R antibodies were positively correlated with fibrinogen, D-dimer, K time, CI value, α-angle, and MA value. Multiple linear regression analysis indicated that anti-PLA2R antibodies were independently correlated with fibrinogen and MA value. CONCLUSION: Our study provides a new perspective on the underlying mechanisms of hypercoagulability in patients with IMN. Anti-PLA2R antibodies are associated with hypercoagulability in patients with IMN and may affect coagulation in patients with IMN by affecting platelet aggregation function and fibrinogen counts.
Assuntos
Autoanticorpos , Glomerulonefrite Membranosa , Receptores da Fosfolipase A2 , Trombofilia , Humanos , Receptores da Fosfolipase A2/imunologia , Glomerulonefrite Membranosa/sangue , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/complicações , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Trombofilia/etiologia , Trombofilia/imunologia , Trombofilia/sangue , Autoanticorpos/sangueRESUMO
AIM: Rhodojaponin VI (R-VI) is the key compound of Rhododendron molle G. Don (Ericaceae) (RM) with effective clinical application in rheumatoid arthritis and chronic glomerulonephritis. In our study, we tried to explore the effect of R-VI on the rat model of membranous nephropathy. METHODS: The rat model of passive heymann nephritis (PHN) was established by injecting sheep anti-rat Fx1A serum at a single dose through the tail. The rats were orally administered R-VI (0.02 mg/kg) or FK506 (1 mg/kg) 1 day before PHN induction, which was kept for 4 weeks. Urine and blood samples as well as kidney tissue were collected for analysis. C5b-9-induced human podocyte cell (HPC) was employed for experiments in vitro. RESULTS: R-VI could alleviate glomerulonephritis progression and podocyte injury in PHN rats, as indicated by the decreased proteinuria and the elevated level of albumin, accompanied with reduced immune deposits, reversed podocyte injury in the kidneys. Furthermore, R-VI suppressed murine double minute 2 (MDM2) expression without the alteration in the protein level of p53 and decreased Notch1 expression independent of Numb regulation. Pre-treatment with R-VI in C5b-9-induced HPC blocked MDM2/Notch1 signalling pathway. CONCLUSION: Thus, R-VI ameliorates podocyte injury in rats with PHN, which was probably related with MDM2/Notch1 signalling pathway.
Assuntos
Modelos Animais de Doenças , Glomerulonefrite Membranosa , Podócitos , Proteínas Proto-Oncogênicas c-mdm2 , Receptor Notch1 , Saponinas , Transdução de Sinais , Animais , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/metabolismo , Podócitos/efeitos dos fármacos , Podócitos/patologia , Podócitos/metabolismo , Receptor Notch1/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Humanos , Saponinas/farmacologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The differentiation between primary and secondary forms of membranous nephropathy (MN) is a cornerstone that is necessary for adequate decision making regarding the treatment options and behavior of each specific case. Kidney biopsy and antibody results can be controversial, and a unique biomarker has still not been found. BACKGROUND AND OBJECTIVES: We investigated the lack of mannose-binding lectin (MBL) deposition in patients with secondary MNs (sMNs) with the presence of IgG4 deposition in relation to the presence of MBL deposition in patients with primary MNs (pMNs). We also established a connection between the stage of MN and MBL deposition. MATERIALS AND METHODS: Materials from 72 renal biopsies with proven MN were used for immunohistochemistry staining (IHC) for the phospholipase A2 receptor (PLA2R), immunoglobulin subtype IgG4, and MBL. Patients were separated into one of the following three groups: primary MN (pMN), idiopathic MN (iMN), and secondary MN (sMN). Serum antibodies for PLA2R and thrombospondin type-I-domain-containing 7A (THSD7A) were also used for the precise evaluation of the type of MN, as well as for detecting positivity for PLA2R using IHC. Which stage of MN was present in relation to the deposition of MBL was evaluated. RESULTS: In total, 50 patients were positive for IgG4, 34 with pMN, 12 with iMN, and 4 with sMN. A total of 20 patients were positive for MBL, 14 with pMN and 6 with iMN; no MBL deposits were found in patients with sMN. MBL positivity was predominantly present in the first two stages of MN, with a gradual reduction in the later stages. CONCLUSIONS: The activation of the lectin-complement pathway occurs in the early stages of the disease and is associated with the deposition of IgG4; IgG4 deposition is present in sMN, but there is no MBL deposition. IgG4 cannot be used for the differentiation of primary from secondary MNs, but the lack of MBL can be used as a marker for sMN in the early stages of the disease.
Assuntos
Glomerulonefrite Membranosa , Imunoglobulina G , Lectina de Ligação a Manose , Receptores da Fosfolipase A2 , Humanos , Glomerulonefrite Membranosa/metabolismo , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/diagnóstico , Masculino , Feminino , Lectina de Ligação a Manose/metabolismo , Pessoa de Meia-Idade , Imunoglobulina G/metabolismo , Imunoglobulina G/imunologia , Adulto , Receptores da Fosfolipase A2/metabolismo , Receptores da Fosfolipase A2/imunologia , Biomarcadores , Idoso , Trombospondinas/metabolismo , Rim/metabolismo , Rim/patologia , BiópsiaRESUMO
BACKGROUND: This study performs a detailed bioinformatics and machine learning analysis to investigate the genetic foundations of membranous nephropathy (MN) in lung adenocarcinoma (LUAD). METHODS: In this study, the gene expression profiles of MN microarray datasets (GSE99339) and LUAD dataset (GSE43767) were downloaded from the Gene Expression Omnibus database, common differentially expressed genes (DEGs) were obtained using the limma R package. The biological functions were analyzed with R Cluster Profiler package according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Machine learning algorithms, including LASSO regression, support vector machine (SVM), Random Forest, and Boruta analysis, were applied to identify hubgenes linked to LUAD-associated MN. These genes' prognostic values were evaluated in the TCGA-LUAD cohort and validated through immunohistochemistry on renal biopsy specimens. RESULTS: A total of 36 DEGs in common were identified for downstream analyses. Functional enrichment analysis highlighted the involvement of the Toll-like receptor 4 pathway and several immune recognition pathways in LUAD-associated MN. COL3A1, PSENEN, RACGAP1, and TNFRSF10B were identified as hub genes in LUAD-associated MN using machine learning algorithms. ROC analysis demonstrated their effective discrimination of MN with high accuracy. Survival analysis showed that lung adenocarcinoma patients with higher expression of these genes had significantly reduced overall survival. In patients with lung adenocarcinoma-associated MN, RACGAP1, COL3A1, PSENEN, and TNFRSF10B were higher expressed in the glomerular, especially RACGAP1, indicating an important role in the pathogenesis of LUAD-associated membranous nephropathy. CONCLUSIONS: Our study underscores the critical role of RACGAP1, COL3A1, PSENEN, and TNFRSF10B in the development of LUAD-associated MN, providing important insights for future research and the development of potential therapeutic strategies.
Assuntos
Adenocarcinoma de Pulmão , Biologia Computacional , Glomerulonefrite Membranosa , Neoplasias Pulmonares , Aprendizado de Máquina , Humanos , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/imunologia , Adenocarcinoma de Pulmão/genética , Biologia Computacional/métodos , Neoplasias Pulmonares/genética , Proteínas Ativadoras de GTPase/genética , Regulação Neoplásica da Expressão Gênica , Prognóstico , Masculino , Feminino , Perfilação da Expressão Gênica , Bases de Dados Genéticas , Pessoa de Meia-Idade , Colágeno Tipo IIIRESUMO
INTRODUCTION: Patients with resolved hepatitis B virus infection undergoing rituximab are at risk of hepatitis B virus reactivation without antiviral prophylaxis. However, the risk in such patients treated with rituximab-based regimens for membranous nephropathy is not clear. We evaluated the risk of hepatitis B virus reactivation in membranous nephropathy patients with resolved infection undergoing rituximab-based regimens without antiviral prophylaxis. METHODS: Clinical data of 51 membranous nephropathy patients with resolved hepatitis B virus infection undergoing rituximab-based regimens without antiviral prophylaxis were retrospectively analyzed. Among these, 21 patients were followed for more than 1 year after rituximab discontinuation. The clinical data collected aimed to assess patients' responses and the risk of hepatitis B virus reactivation during and after rituximab treatment. RESULTS: 30/51 (58.8 %) patients reached complete or partial remission at 12 months. None of the patients experienced HBsAg seroreversion during rituximab treatment. Alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and total bilirubin levels, as well as the numbers of patients who exceeded the upper limits of normal for alkaline phosphatase and prothrombin time, did not show any statistically significant difference during rituximab-based therapy. Neither did the anti-HBs level, the number of patients with protective anti-HBs titers exceeding 10 U/L, nor the levels of CD19+ B cells, CD4+ T cells, CD8+ T cells, and natural killer cells. Among the 21 patients followed for 12 (ranging from 12 to 19) months after rituximab discontinuation, no hepatitis B virus reactivation was observed. The mean anti-HBs level and the number of patients with anti-HBs titers over 10 U/L did not show any statistically significant difference during the extended follow-up of 33 patient-years. Neither did the CD4+ T cell, CD8+ T cell, nor the natural killer cell counts. One patient presented with an ALT level that exceeded the baseline value by three times and reached above 100 U/L, accompanied by elevations in AST, GGT, and ALP levels. Meanwhile, the anti-HBs titer was 816.09 U/L, and HBsAg was negative. CONCLUSION: The administration of rituximab-based regimens in membranous nephropathy patients with hepatitis B virus resolved infection leads to a low risk of hepatitis B virus reactivation without antiviral prophylaxis. Patient's immune status, drug combination, rituximab strategy should be fully evaluated when considering antiviral prophylaxis therapy.
Assuntos
Glomerulonefrite Membranosa , Vírus da Hepatite B , Hepatite B , Rituximab , Ativação Viral , Humanos , Rituximab/uso terapêutico , Rituximab/efeitos adversos , Masculino , Feminino , Hepatite B/imunologia , Hepatite B/tratamento farmacológico , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/virologia , Ativação Viral/efeitos dos fármacos , Pessoa de Meia-Idade , Vírus da Hepatite B/fisiologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/imunologia , Estudos Retrospectivos , Adulto , Idoso , Antivirais/uso terapêuticoRESUMO
Kimura's disease (KD) is a chronic inflammatory disorder characterized by nontender lymphadenopathy involving the head and neck region. Renal involvement in KD is rare, especially in children. We report a 12-year-old boy who had been previously treated for classical KD and had presented with anasarca and oliguria after 4 years. There were no swellings or lymphadenopathy. The kidney biopsy revealed membranous nephropathy. Remission was achieved with oral prednisolone and tacrolimus therapy. This patient highlights the need to regularly monitor patients with KD for the evolution of renal diseases, even if lymphadenopathy regresses. Serial monitoring for eosinophilia, inflammatory markers, and urine examination is needed to help identify subclinical disease early and prompt initiation of specific therapy.
Assuntos
Glomerulonefrite Membranosa , Imunossupressores , Doença de Kimura , Prednisolona , Tacrolimo , Humanos , Masculino , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Criança , Doença de Kimura/diagnóstico , Doença de Kimura/complicações , Doença de Kimura/tratamento farmacológico , Biópsia , Imunossupressores/uso terapêutico , Resultado do Tratamento , Prednisolona/uso terapêutico , Tacrolimo/uso terapêutico , Indução de Remissão , Rim/patologia , Quimioterapia Combinada , Glucocorticoides/uso terapêuticoRESUMO
CONTEXT: Four algorithms with relatively balanced complexity and accuracy in deep learning classification algorithm were selected for differential diagnosis of primary membranous nephropathy (PMN). OBJECTIVE: This study explored the most suitable classification algorithm for PMN identification, and to provide data reference for PMN diagnosis research. METHODS: A total of 500 patients were referred to Luo-he Central Hospital from 2019 to 2021. All patients were diagnosed with primary glomerular disease confirmed by renal biopsy, contained 322 cases of PMN, the 178 cases of non-PMN. Using the decision tree, random forest, support vector machine, and extreme gradient boosting (Xgboost) to establish a differential diagnosis model for PMN and non-PMN. Based on the true positive rate, true negative rate, false-positive rate, false-negative rate, accuracy, feature work area under the curve (AUC) of subjects, the best performance of the model was chosen. RESULTS: The efficiency of the Xgboost model based on the above evaluation indicators was the highest, which the diagnosis of PMN of the sensitivity and specificity, respectively 92% and 96%. CONCLUSIONS: The differential diagnosis model for PMN was established successfully and the efficiency performance of the Xgboost model was the best. It could be used for the clinical diagnosis of PMN.
Membranous nephropathy (MN) without obvious causes is called primary MN (PMN), This study utilized deep learning classification algorithms for differential diagnosis of PMN and explored the most suitable classification algorithm for PMN recognition, provided data reference for PMN diagnosis research.
Assuntos
Glomerulonefrite Membranosa , Humanos , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Diagnóstico Diferencial , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Aprendizado de Máquina , Algoritmos , Sensibilidade e Especificidade , Máquina de Vetores de Suporte , Estudos Retrospectivos , Árvores de Decisões , Aprendizado Profundo , BiópsiaRESUMO
BACKGROUND: There have been some shifts in the frequency and distribution of biopsy-proven renal diseases in China over recent years. The aim of the study was to investigate the changing spectrum of renal diseases from the view of kidney biopsy data in a single center of China. METHODS AND RESULTS: A total of 10,996 cases of native renal biopsies from patients aged ≥15 years old in Huashan Hospital, Fudan University, between 2008 and 2018 were analyzed retrospectively. The results showed that primary glomerular nephropathy (PGN) remained the most common biopsy-proven renal disease (69.42% of total), with IgA nephropathy (IgAN) accounting for 44.40% of PGN, membranous nephropathy (MN) for 28.55%, minimal change disease (MCD) for 13.26% and focal segmental glomerulosclerosis (FSGS) for 8.00%. During the study period, the proportion of MN in PGN appeared an increasing tendency, while that of IgAN and MCD remained stable and that of FSGS showed a decline. Secondary glomerular nephropathy (SGN) constituted 21.54% of total cases, among which the leading two diseases were lupus nephritis (LN) and Henoch-Schonlein purpura nephritis (HSN) which accounted for 41.08% and 19.11% respectively. CONCLUSIONS: The 11-year retrospective study revealed that PGN was the predominant histologic diagnosis among patients undergoing renal biopsy and the most frequent type of PGN remained to be IgAN, followed by MN which increased dramatically.
Assuntos
Glomerulonefrite por IGA , Glomerulonefrite Membranosa , Glomerulosclerose Segmentar e Focal , Rim , Nefrose Lipoide , Humanos , China/epidemiologia , Masculino , Estudos Retrospectivos , Adulto , Feminino , Pessoa de Meia-Idade , Biópsia/estatística & dados numéricos , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/epidemiologia , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/epidemiologia , Glomerulosclerose Segmentar e Focal/patologia , Glomerulosclerose Segmentar e Focal/epidemiologia , Adulto Jovem , Nefrose Lipoide/patologia , Nefrose Lipoide/epidemiologia , Rim/patologia , Adolescente , Nefrite Lúpica/patologia , Nefrite Lúpica/epidemiologia , Idoso , Vasculite por IgA/patologia , Vasculite por IgA/epidemiologia , Vasculite por IgA/diagnóstico , Glomerulonefrite/patologia , Glomerulonefrite/epidemiologia , Nefropatias/patologia , Nefropatias/epidemiologia , Nefropatias/diagnósticoRESUMO
Membranous nephropathy is a major etiology of nephrotic syndrome in adults and less frequently in children. Circulating antibodies to intrinsic podocyte antigens, such as M-type phospholipase A2 receptor, or to extrinsic proteins accumulate beneath the podocyte to cause damage via complement activation and/or other mechanisms. The availability of clinical testing for autoantibodies to M-type phospholipase A2 receptor has allowed noninvasive diagnosis of this form of membranous nephropathy and a means to monitor immunologic activity to guide immunosuppressive therapy. Treatment of membranous nephropathy includes optimal supportive care with renin-angiotensin-system blockers, lipid-lowering agents, diuretics, lifestyle changes, and additional immunosuppressive therapy in patients with an increased risk of progression to kidney failure. Rituximab has been recognized as a first-line immunosuppressive therapy for most membranous nephropathy patients with an increased risk of progressive disease, except those with life-threatening nephrotic syndrome or rapidly deteriorating kidney function from membranous nephropathy. This article discusses the major and minor antigens described in membranous nephropathy, the natural history of the disease, and guidelines for clinical management and immunosuppressive treatment.
Assuntos
Glomerulonefrite Membranosa , Imunossupressores , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/terapia , Glomerulonefrite Membranosa/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , Receptores da Fosfolipase A2/imunologia , Autoanticorpos/imunologiaRESUMO
INTRODUCTION: Stroke in young individuals is becoming increasingly prevalent worldwide. Its causes can vary widely, so a thorough investigation by a multidisciplinary team is needed. Pinpointing the precise underlying pathology responsible for the stroke yields benefits for patients, particularly in recurrent events. CASE PRESENTATION: A 38-year-old man presented to the emergency department with symptoms suggestive of stroke, including right hemiparesis, dysarthria, ataxic gait, and right central facial palsy. The brain magnetic resonance image revealed an ischemic lesion located in the left basal ganglia and near the corona radiata. Following an extensive workup, a diagnosis of nephrotic was reached. Histopathology and the exclusion of secondary causes confirmed primary membranous nephropathy as the underlying condition. The patient underwent treatment tailored to address the specific glomerulopathy, along with anticoagulation therapy and immunosuppression as per current guidelines. Subsequent assessments showed stabilization of renal function, resolution of the edema, and the absence of new thromboembolic events during follow-up. CONCLUSION: The nephrotic syndrome should be recognized as a potential underlying cause of stroke in young patients and, therefore, it should be included in the differential diagnosis during the evaluation of patients with coagulopathies. Nephrotic syndrome screening may be done by conducting a simple urinalysis readily available in most healthcare facilities. This underlines the importance of considering renal pathology in the assessment of stroke etiologies, especially when coagulation abnormalities are present.
Introducción. Los eventos cerebrovasculares en los jóvenes son un problema creciente en todo el mundo. Su etiología puede ser variada y requieren un trabajo riguroso de un equipo multidisciplinario. La identificación de la enfermedad específica que conduce al ictus tiene un impacto beneficioso en los pacientes, especialmente en aquellos con eventos recurrentes. Presentación del caso. Se presenta el caso de un hombre de 38 años que acudió al servicio de urgencias con hemiparesia derecha, disartria, ataxia y parálisis facial central derecha. La resonancia magnética cerebral reveló una lesión isquémica localizada en los ganglios basales izquierdos, cerca de la corona radiada. Después de un estudio exhaustivo, se estableció el diagnóstico de síndrome nefrótico. No obstante, al analizar las características histopatológicas y descartar otras causas secundarias, el diagnóstico final fue una nefropatía membranosa primaria. El paciente recibió tratamiento específico para su glomerulopatía, anticoagulación e inmunosupresión según las guías vigentes. Durante el seguimiento, se encontró estabilización de la función renal, el edema se resolvió y no se identificó ningún nuevo evento tromboembólico. Conclusión. El síndrome nefrótico debe considerarse entre las posibles causas del ictus en pacientes jóvenes y debería tenerse en cuenta en los estudios de coagulopatías. El tamizaje de esta enfermedad requiere únicamente un uroanálisis, el cual está disponible en la mayoría de los centros de atención de salud.