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1.
Iran J Kidney Dis ; 18(4): 239-243, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39423097

RESUMO

Fabry disease (FD) is a rare X-linked genetic disease that can coexist with multiple glomerulopathies. We report a 32-year-old female patient of FD coexisting with stage II membranous nephropathy (MN), who presented with proteinuria, normal renal function, and hypo-hidrosis as the only symptom. The renal biopsy manifested a subepithelial immunocomplex deposit in the glomeruli along with basement membrane thickening on light microscopy. Electron microscopy revealed myeloid bodies in some podocytes, which suggested the patient possibly coexistence with Fabry disease. The low activity of α-galactosidase A and one pathogenic heterozygous mutation (c.335G > Ap.Arg112His) in the α-galactosidase A gene confirmed the diagnosis of Fabry disease. This patient's son had the same gene mutation as his mother but without any symptoms at the time. Treatment with ramipril turned urine protein negative. The proteinuria had reoccurred, as shown by the presence of foamy urine, a protein to creatinine ratio of 1.54 g/g, and a blood albumin level of 34.4g/L. The patient was being treated with allisartan isoproxil. However, at the time, the urine protein did not turn negative.


Assuntos
Doença de Fabry , Glomerulonefrite Membranosa , Humanos , Doença de Fabry/complicações , Doença de Fabry/genética , Doença de Fabry/diagnóstico , Doença de Fabry/tratamento farmacológico , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Adulto , Feminino , alfa-Galactosidase/genética , alfa-Galactosidase/uso terapêutico , Biópsia , Proteinúria/etiologia , Mutação , Glomérulos Renais/patologia , Glomérulos Renais/ultraestrutura
2.
Ter Arkh ; 96(6): 580-586, 2024 Jul 07.
Artigo em Russo | MEDLINE | ID: mdl-39106498

RESUMO

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; р=0.07), FSGS (OR 0.05, 95% CI 0.01-0.34; р=0.002) и response to initial course of immunosuppression (OR 0.33, 95% CI 0.12-0.95; р=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/fisiopatologia
3.
Ren Fail ; 46(2): 2391069, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39143819

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/patologia
4.
FP Essent ; 543: 18-23, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39163011

RESUMO

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.


Assuntos
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/etiologia
5.
Kidney Int ; 106(5): 907-912, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39197586

RESUMO

Membranous nephropathy (MN) results from accumulation of antigen-antibody immune complexes along the subepithelial region of the glomerular basement membranes. Over the last years, 13 target antigens have been discovered and include PLA2R, THSD7A, EXT1 and EXT2, NELL1, SEMA3B, NCAM1, CNTN1, HTRA1, FAT1, PCDH7, NTNG1, PCSK6 and NDNF, accounting for 80-90% of MN antigens. MN associated with many of these antigens have distinctive clinicopathologic findings. It is important to accurately identify the antigen in MN. Immunohistochemical (IHC) and/or immunofluorescence (IF) methods are currently used to detect PLA2R, THSD7A, NELL1, SEMA3B and EXT1/EXT2. However, for the remaining antigens, IHC/IF methods do not exist and are not practical for detection. Here, we developed laser microdissection-based mass spectrometry methodology (LMD/MS) as a one-stop clinical test for the detection of MN antigens using paraffin-embedded kidney biopsy tissue. The LMD/MS test was validated in two steps. LMD/MS was used to detect the antigen in 75 cases of MN with known antigens and correctly identified the antigen in all these cases. Next, LMD/MS was used to identify the antigen in 61 MN cases where the antigen was unknown and identified one of the known antigens in 40 of 61 cases including many of the less common antigens. This lower-than-expected detection rate is explained by intentional enrichment of the cohort with PLA2R-negative MN. Overall, PLA2R was identified in 16.4%, one of the other antigens detected in 49.1%, and in the remaining 34.5% of cases, none of the above antigens was detected. Thus, LMD/MS is an extremely useful and reliable method for the detection of known MN antigens and possibly indicating an unknown MN antigen for eventual discovery.


Assuntos
Glomerulonefrite Membranosa , Microdissecção e Captura a Laser , Humanos , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Biópsia , Adulto , Reprodutibilidade dos Testes , Inclusão em Parafina , Idoso , Autoantígenos/imunologia , Autoantígenos/análise , Espectrometria de Massas/métodos
6.
Int J Rheum Dis ; 27(7): e15265, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39030988

RESUMO

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 terapêutico
7.
Ren Fail ; 46(2): 2380752, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39039848

RESUMO

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 , Biópsia
8.
Zhonghua Nei Ke Za Zhi ; 63(8): 816-820, 2024 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-39069874

RESUMO

A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient's nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 µmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5➝147 µmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 µmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.


Assuntos
Edema , Glomerulonefrite Membranosa , Síndrome Nefrótica , Proteinúria , Humanos , Masculino , Adulto , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/diagnóstico , Edema/tratamento farmacológico , Edema/diagnóstico , Rituximab/uso terapêutico , Extremidade Inferior , Anticorpos Monoclonais Humanizados/uso terapêutico
9.
BMC Nephrol ; 25(1): 225, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009965

RESUMO

BACKGROUND: Membranous nephropathy (MN) is a common type of nephrotic syndrome (NS) in adults, accounting for about 20-30% of cases. Although secondary to specific factors, the coexistence of MN and mantle cell lymphoma (MCL) has been scarcely reported in clinical literature. CASE PRESENTATION: A 59-year-old Chinese male was admitted to the hospital with a generalized pruritic rash with bilateral lower extremity edema, which did not improve significantly after symptomatic treatment. He had undergone renal biopsy, and the diagnosis was thought to be secondary MN (SMN), therefore, we did a lymph node biopsy on the patient and found that MN was complicated with MCL. Soon after, the patient was admitted to the hematology department for a BR chemotherapy regimen (composed of bendamustine 90 mg/m2 BSA (body surface area), rituximab 375 mg/m2 BSA and dexamethasone 5 mg), and during the post-treatment follow-up, both his symptoms and renal function improved. CONCLUSIONS: The mechanism underlying the combination of SMN and MCL remains elusive and exceedingly rare, consequently often overlooked in clinical practice. This case serves to offer valuable clinical insights for diagnosis and treatment, while emphasizing the pivotal role of renal pathology in clinical assessment.


Assuntos
Exantema , Síndrome Nefrótica , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/complicações , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/etiologia , Síndrome Nefrótica/tratamento farmacológico , Exantema/etiologia , Exantema/tratamento farmacológico , Linfoma de Célula do Manto/complicações , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/diagnóstico , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/tratamento farmacológico , Rituximab/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Cloridrato de Bendamustina/uso terapêutico , Cloridrato de Bendamustina/administração & dosagem
10.
Front Immunol ; 15: 1404954, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39072328

RESUMO

Introduction: Kimura's disease (KD) is a rare chronic inflammatory disorder characterized by subcutaneous lymphoid hyperplasia with peripheral eosinophilia. Kidney involvement is reported in 15%-18% of adult patients with KD, in many cases as nephrotic syndrome. We present a case of overlapping membranous nephropathy and IgA nephropathy associated with KD. Case report: A 27-year-old man was admitted with a history of bilateral leg edema for the last 2 months and concomitant progressive increase of cervical mass and fever. Laboratory findings were as follows: peripheral leukocyte count, 10,080/mm³; eosinophils, 3,200/mm³ (31.7%); serum creatinine, 0.83 mg/dL; and eGFR: 140 mL/min per 1.73 m2. Urinalysis revealed the presence of hematuria and proteinuria and the following results: 24-h proteinuria, 12.9 g; serum albumin, 1.3 g/dL; and elevated IgE level, 750 kU/L. Serologies for hepatitis B, hepatitis C, HIV, and VDRL were all negative. Complement C3 and C4 levels were normal. No monoclonal protein was detected in blood and urine. Parasite infestation was discarded. A biopsy of the cervical lymph node revealed eosinophilic lymphoid hyperplasia, suggesting KD. A kidney biopsy revealed findings consistent with the overlapping of membranous nephropathy with IgA nephropathy. The patient was treated for KD with prednisone 1 mg/kg/d with progressive dose tapering and posterior association of methotrexate 15 mg/week. A renin-angiotensin system inhibitor was prescribed for nephrotic syndrome. The cervical mass regressed, and proteinuria achieved partial remission, with an increase in serum albumin level and normalization of eosinophils and IgE levels. Conclusion: Although uncommon, kidney involvement must be considered in patients with KD. Glomerular diseases are the most frequent form of kidney injury.


Assuntos
Glomerulonefrite por IGA , Glomerulonefrite Membranosa , Doença de Kimura , Humanos , Adulto , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/tratamento farmacológico , Masculino , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/imunologia , Doença de Kimura/diagnóstico , Doença de Kimura/complicações , Doença de Kimura/tratamento farmacológico , Biópsia , Rim/patologia
11.
Int J Mol Sci ; 25(14)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39062903

RESUMO

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 , Biópsia
12.
BMC Nephrol ; 25(1): 204, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907217

RESUMO

BACKGROUND: The concomitant occurrence of membranous nephropathy and anti-glomerular basement (anti-GBM) disease has been previously described but is extremely rare. However, delayed recognition or misdiagnosis leads to delayed treatment, resulting in worse renal and patient outcomes. CASE PRESENTATION: We present 3 patients with rapidly progressive glomerulonephritis (RPGN), anti-GBM and serum-positive M-type phospholipase A2 receptor (anti-PLA2R) antibody. Renal biopsies revealed PLA2R-associated membranous nephropathy with anti-GBM glomerulonephritis. We analyzed the clinical and pathological characteristics and discussed that the correct diagnosis of membranous nephropathy with anti-GBM should rely on a combination of renal biopsy findings and serological testing. Despite aggressive treatment, one patient received maintenance hemodialysis, one patient progressed to CKD 3 stage, and the other patient died of cerebral infarction. CONCLUSION: The simultaneous occurrence of membranous nephropathy and anti-GBM disease is extremely rare. The correct diagnosis of membranous nephropathy with anti-GBM relies on a combination of renal biopsy findings and serological testing. Early diagnosis is needed to improve the renal dysfunction.


Assuntos
Doença Antimembrana Basal Glomerular , Glomerulonefrite Membranosa , Receptores da Fosfolipase A2 , Humanos , Doença Antimembrana Basal Glomerular/diagnóstico , Doença Antimembrana Basal Glomerular/complicações , Doença Antimembrana Basal Glomerular/terapia , Autoanticorpos/sangue , Biópsia , Glomerulonefrite/diagnóstico , Glomerulonefrite/complicações , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/imunologia , Receptores da Fosfolipase A2/imunologia
14.
Medicina (B Aires) ; 84(3): 468-473, 2024.
Artigo em Espanhol | MEDLINE | ID: mdl-38907960

RESUMO

INTRODUCTION: Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome in adults (20-30%). Light microscopy shows thickening of glomerular basement membrane with appearance of spikes. These histological findings are not evident in early forms, in which case the granular deposition pattern of IgG and/or C3 in the basement membrane by immunofluorescence (IF) constitutes the diagnostic tool that allows to differentiate it from minimal change disease (MCD). Complement system plays a key role in the pathophysiology of MN. C4d is a degradation product and a marker of the complement system activation. C4d labelling by immunohistochemical (HI) technique can help in the differential diagnosis between both glomerulopathies NM and MCD when the material for IF is insufficient and light microscopy is normal. Our objective was to explore the discrimination power of C4d to differentiate between MN and MCD in renal biopsy material. METHODS: Paraffin-embedded samples were recovered from renal biopsies with a diagnosis of MN and MCD performed between 1/1/2008 and 4/1/2019. IH staining was performed by immunoperoxidase technique using a rabbit anti-human C4d polyclonal antibody. RESULTS: In all cases with MN (n = 27, 15 males) with a median age of 63 (range: 18-87) years, C4d deposits were detected. In 21 cases with MCD (12 males) with a median age of 51 (range: 18-87) years, the C4d marking was negative in every samples. CONCLUSION: The results indicate that the marking of the renal biopsy with C4d is a useful tool for the differential diagnosis between NM and MCD.


Introducción: La nefropatía membranosa (NM) es la causa más frecuente de síndrome nefrótico primario en adultos (20-30%). En la microscopia óptica se observa engrosamiento de membrana basal glomerular con aparición de espigas. Estos hallazgos histológicos no son evidentes en formas tempranas, en cuyo caso el patrón de depósito granular de IgG y/o C3 en la membrana basal por inmunofluorescencia (IF) permite diferenciarla de enfermedad por cambios mínimos (ECM). El sistema del complemento juega un papel central en la fisiopatología de la NM. C4d es producto de degradación y un marcador de la activación del complemento. La marcación con C4d en muestras de biopsias renales, por técnica de inmunohistoquímica (IH) puede colaborar en el diagnóstico diferencial entre ambas glomerulopatías. Nuestro objetivo fue explorar el poder de discriminación del C4d para diferenciar NM de ECM en material de biopsias renales. Métodos: Se recuperaron muestras en parafina de biopsias renales con diagnóstico de NM y ECM realizados entre 1/1/2008 y 1/4/2019. Se realizaron tinciones de IH por técnica de inmunoperoxidasa con C4d usando un anticuerpo policlonal antihumano de conejo. Resultados: En todos los casos con NM (n = 27, 15 hombres) con mediana de edad de 63 (rango: 18-86) años se detectaron depósitos de C4d. En los 21 casos con ECM (12 hombres) con mediana de edad de 51 (rango: 18-87) años la marcación de C4d fue negativa. Conclusión: Los resultados indican que la marcación de la biopsia renal con C4d es una herramienta útil para el diagnóstico diferencial entre NM y ECM.


Assuntos
Complemento C4b , Glomerulonefrite Membranosa , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/imunologia , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Idoso , Complemento C4b/análise , Adulto Jovem , Diagnóstico Diferencial , Idoso de 80 Anos ou mais , Adolescente , Biópsia , Biomarcadores/análise , Nefrose Lipoide/patologia , Nefrose Lipoide/diagnóstico , Fragmentos de Peptídeos/análise , Estudos Retrospectivos
15.
Front Immunol ; 15: 1302909, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846934

RESUMO

Background: Membranous nephropathy (MN) is an autoimmune disease and represents the most prevalent type of renal pathology in adult patients afflicted with nephrotic syndrome. Despite substantial evidence suggesting a possible link between MN and cancer, the precise underlying mechanisms remain elusive. Methods: In this study, we acquired and integrated two MN datasets (comprising a single-cell dataset and a bulk RNA-seq dataset) from the Gene Expression Omnibus database for differential expression gene (DEG) analysis, hub genes were obtained by LASSO and random forest algorithms, the diagnostic ability of hub genes was assessed using ROC curves, and the degree of immune cell infiltration was evaluated using the ssGSEA function. Concurrently, we gathered pan-cancer-related genes from the TCGA and GTEx databases, to analyze the expression, mutation status, drug sensitivity and prognosis of hub genes in pan-cancer. Results: We conducted intersections between the set of 318 senescence-related genes and the 366 DEGs, resulting in the identification of 13 senescence-related DEGs. Afterwards, we meticulously analyzed these genes using the LASSO and random forest algorithms, which ultimately led to the discovery of six hub genes through intersection (PIK3R1, CCND1, TERF2IP, SLC25A4, CAPN2, and TXN). ROC curves suggest that these hub genes have good recognition of MN. After performing correlation analysis, examining immune infiltration, and conducting a comprehensive pan-cancer investigation, we validated these six hub genes through immunohistochemical analysis using human renal biopsy tissues. The pan-cancer analysis notably accentuates the robust association between these hub genes and the prognoses of individuals afflicted by diverse cancer types, further underscoring the importance of mutations within these hub genes across various cancers. Conclusion: This evidence indicates that these genes could potentially play a pivotal role as a critical link connecting MN and cancer. As a result, they may hold promise as valuable targets for intervention in cases of both MN and cancer.


Assuntos
Glomerulonefrite Membranosa , Humanos , Glomerulonefrite Membranosa/genética , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/metabolismo , Perfilação da Expressão Gênica , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/metabolismo , Biologia Computacional/métodos , Prognóstico , Biomarcadores Tumorais/genética , Transcriptoma , Redes Reguladoras de Genes , Biomarcadores , Bases de Dados Genéticas
16.
Ren Fail ; 46(1): 2355353, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38785304

RESUMO

BACKGROUND: This study aims to investigate the incidence and prognosis of malignancy in individuals with thrombospondin type-1 domain-containing 7A (THSD7A)-associated membranous nephropathy (MN). METHODS: First, we performed a systematic literature review of prevalence of malignancy in THSD7A-associated MN. Then, we conducted a retrospective analysis of 454 patients diagnosed with MN through renal biopsy at our hospital between January 2016 and December 2020. We assessed the presence of serum anti-THSD7A antibodies and performed immunohistochemical staining of renal tissue for THSD7A. Subsequently, we followed patients with THSD7A-associated MN for a minimum of 3-5 years, collecting their clinical, pathological characteristics, and prognosis. Additionally, we conducted a literature review on patients with THSD7A-associated MN in conjunction with malignancy. RESULTS: We identified a total of nine articles containing comprehensive data on THSD7A-associated MN and malignancy. Among 235 patients with THSD7A-positive MN, 36 individuals had concurrent malignancies, resulting in a malignancy prevalence of 13.3% (95% CI: 8.9-17.7%). In our center, we followed up with 15 patients diagnosed with THSD7A-associated MN and observed three cases of concomitant tumors: two cases of lung adenocarcinoma and one case of small cell lung cancer with multiple metastases. The prevalence of malignancy in our cohort was 20%. Notably, we detected positive THSD7A staining in both renal and lung cancer tissues in one patient with small cell lung cancer. CONCLUSIONS: Patients with THSD7A-associated MN should undergo vigilant follow-up assessments, with a particular focus on actively seeking potential tumorigenic lesions to prevent misdiagnosis or oversight.


Assuntos
Glomerulonefrite Membranosa , Trombospondinas , Humanos , Glomerulonefrite Membranosa/epidemiologia , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/diagnóstico , Prognóstico , Trombospondinas/imunologia , Prevalência , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Neoplasias/epidemiologia , Idoso , Rim/patologia
17.
Int J Med Sci ; 21(7): 1292-1301, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818472

RESUMO

Objective: This study aimed to build and validate a practical web-based dynamic prediction model for predicting renal progression in patients with primary membranous nephropathy (PMN). Method: A total of 359 PMN patients from The First Affiliated Hospital of Fujian Medical University and 102 patients with PMN from The Second Hospital of Longyan between January 2018 to December 2023 were included in the derivation and validation cohorts, respectively. Renal progression was delineated as a decrease in eGFR of 30% or more from the baseline measurement at biopsy or the onset of End-Stage Renal Disease (ESRD). Multivariable Cox regression analysis was employed to identify independent prognostic factors. A web-based dynamic prediction model for renal progression was built and validated, and the performance was assessed using. An analysis of the receiver operating characteristic and the decision curve analysis. Results: In the derivation cohort, 66 (18.3%) patients experienced renal progression during the follow-up period (37.60 ± 7.95 months). The final prediction rule for renal progression included hyperuricemia (HR=2.20, 95%CI 1.26 to 3.86), proteinuria (HR=2.16, 95%CI 1.47 to 3.18), significantly lower serum albumin (HR=2.34, 95%CI 1.51 to 3.68) and eGFR (HR=1.96, 95%CI 1.47 to 2.61), older age (HR=1.85, 95%CI 1.28 to 2.61), and higher sPLA2R-ab levels (HR=2.08, 95%CI 1.43 to 3.18). Scores for each variable were calculated using the regression coefficients in the Cox model. The developed web-based dynamic prediction model, available online at http://imnpredictmodel1.shinyapps.io/dynnomapp, showed good discrimination (C-statistic = 0.72) and calibration (Brier score, P = 0.155) in the validation cohort. Conclusion: We developed a web-based dynamic prediction model that can predict renal progression in patients with PMN. It may serve as a helpful tool for clinicians to identify high-risk PMN patients and tailor appropriate treatment and surveillance strategies.


Assuntos
Progressão da Doença , Taxa de Filtração Glomerular , Glomerulonefrite Membranosa , Humanos , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Prognóstico , Falência Renal Crônica , Receptores da Fosfolipase A2/imunologia , Estudos Retrospectivos , Rim/patologia , Rim/fisiopatologia , Fatores de Risco , Curva ROC , Proteinúria
18.
In Vivo ; 38(3): 1503-1508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688636

RESUMO

BACKGROUND/AIM: Membranous nephropathy (MN) is a nephrotic syndrome with both idiopathic and secondary etiologies. The mechanism of cancer-associated MN is presumed to involve the immunological production of antibodies against a tumor antigen, although little is known about the detailed mechanism. Lung cancer is a major neoplasm associated with cancer-associated MN. However, the simultaneous occurrence of secondary MN in patients with cancer of unknown primary (CUP) remains unclear. CASE REPORT: Here, we present a case of secondary MN in a 72-year-old female as a paraneoplastic syndrome in CUP. Thoracic radiotherapy up to a total of 60 Gy was initially performed on the right subclavian and mediastinal lymph nodes. Computed tomography revealed marked shrinking of these lymph nodes, and the secondary MN also improved without any symptoms. CONCLUSION: The presence of proteinuria in patients with CUP suggests the possibility of secondary MN as a rare differential diagnosis.


Assuntos
Glomerulonefrite Membranosa , Neoplasias Primárias Desconhecidas , Síndromes Paraneoplásicas , Humanos , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/etiologia , Glomerulonefrite Membranosa/complicações , Idoso , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/patologia , Feminino , Neoplasias Primárias Desconhecidas/complicações , Neoplasias Primárias Desconhecidas/diagnóstico , Tomografia Computadorizada por Raios X , Diagnóstico Diferencial
19.
Kidney Blood Press Res ; 49(1): 345-354, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38615671

RESUMO

INTRODUCTION: This study evaluated the phenotypic and pathology characteristics of patients undergoing kidney biopsy at a single center, while also determining the frequency and factors associated with clinical outcomes. METHODS: The incidence and distribution of biopsy-proven kidney diseases in 2000-2019 were surveyed. Consecutive individuals diagnosed with membranous nephropathy (MN), immunoglobulin A nephropathy (IgAN), and minimal change disease (MCD) between August 2015 and December 2019 were enrolled in the prospective 2-year follow-up study. Outcomes included remission of proteinuria and kidney disease progression events. Multivariable-adjusted Cox proportional hazards model was applied. RESULTS: 4,550 kidney biopsies were performed in 2000-2019, showing a noticeable increase in the proportion of MN. 426 patients were enrolled in the follow-up cohort. 346 (81.2%) achieved remission of proteinuria, 39 (9.2%) suffered kidney disease progression and 51.3% of them were diagnosed with IgAN. Kidney pathological diagnosis (MN vs. MCD: hazard ratio [HR], 0.42; 95% confidence interval [95% CI], 0.31-0.57; IgAN vs. MCD: 0.58; 0.39-0.85), levels of 24-h urine protein at biopsy (1.04; 1.00-1.08) and presence of nodular mesangial sclerosis (0.70; 0.49-0.99) were significantly correlated with remission of proteinuria after adjusting for baseline variables. 24-h urine protein levels at biopsy (1.14; 1.04-1.25) and the presence of crescents (2.30; 1.06-4.95) were the independent risk factors for kidney disease progression events after adjusting for baseline variables. CONCLUSION: The increasing frequency of MN has been affirmed over the past 2 decades. The therapeutic status, clinical outcomes, and factors influencing these outcomes were presented in this single-center study for the three primary glomerular diseases.


Assuntos
Progressão da Doença , Glomerulonefrite por IGA , Glomerulonefrite Membranosa , Rim , Nefrose Lipoide , Humanos , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/diagnóstico , Glomerulonefrite por IGA/patologia , Glomerulonefrite por IGA/diagnóstico , Nefrose Lipoide/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Biópsia , Rim/patologia , Estudos Prospectivos , Seguimentos , Proteinúria/etiologia
20.
Am J Kidney Dis ; 84(2): 205-214.e1, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38452919

RESUMO

RATIONALE & OBJECTIVE: Glomerular disorders have a highly variable clinical course, and biomarkers that reflect the molecular mechanisms underlying their progression are needed. Based on our previous work identifying plasminogen as a direct cause of podocyte injury, we designed this study to test the association between urine plasmin(ogen) (ie, plasmin and its precursor plasminogen) and end-stage kidney disease (ESKD). STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 1,010 patients enrolled in the CureGN Cohort with biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A nephropathy). PREDICTORS: The main predictor was urine plasmin(ogen) at baseline. Levels were measured by an electrochemiluminescent immunoassay developed de novo. Traditional clinical and analytical characteristics were used for adjustment. The ratio of urine plasmin(ogen)/expected plasmin(ogen) was evaluated as a predictor in a separate model. OUTCOME: Progression to ESKD. ANALYTICAL APPROACH: Cox regression was used to examine the association between urinary plasmin(ogen) and time to ESKD. Urinary markers were log2 transformed to approximate normal distribution and normalized to urinary creatinine (Log2uPlasminogen/cr, Log2 urinary protein/cr [UPCR]). Expected plasmin(ogen) was calculated by multiple linear regression. RESULTS: Adjusted Log2uPlasminogen/cr was significantly associated with ESKD (HR per doubling Log2 uPlasminogen/cr 1.31 [95% CI, 1.22-1.40], P<0.001). Comparison of the predictive performance of the models including Log2 uPlasminogen/cr, Log2 UPCR, or both markers showed the plasmin(ogen) model superiority. The ratio of measured/expected urine plasmin(ogen) was independently associated with ESKD: HR, 0.41 (95% CI, 0.22-0.77) if ratio<0.8 and HR 2.42 (95% CI, 1.54-3.78) if ratio>1.1 (compared with ratio between 0.8 and 1.1). LIMITATIONS: Single plasmin(ogen) determination does not allow for the study of changes over time. The use of a cohort of mostly white patients and the restriction to patients with 3 glomerular disorders limits the external validity of our analysis. CONCLUSIONS: Urinary plasmin(ogen) and the ratio of measured/expected plasmin(ogen) are independently associated with ESKD in a cohort of patients with glomerular disease. Taken together with our previous experimental findings, urinary plasmin(ogen) could be a useful biomarker in prognostic decision making and a target for the development of novel therapies in patients with proteinuria and glomerular disease. PLAIN-LANGUAGE SUMMARY: Glomerular diseases are an important cause of morbidity and mortality in patients of all ages. Knowing the individual risk of progression to dialysis or transplantation would help to plan the follow-up and treatment of these patients. Our work studies the usefulness of urinary plasminogen as a marker of progression in this context, since previous studies indicate that plasminogen may be involved in the mechanisms responsible for the progression of these disorders. Our work in a sample of 1,010 patients with glomerular disease demonstrates that urinary plasminogen (as well as the ratio of measured to expected plasminogen) is associated with the risk of progression to end-stage kidney disease. Urine plasminogen exhibited good performance and, if further validated, could enable risk stratification for timely interventions in patients with proteinuria and glomerular disease.


Assuntos
Biomarcadores , Progressão da Doença , Falência Renal Crônica , Plasminogênio , Humanos , Masculino , Feminino , Biomarcadores/urina , Plasminogênio/urina , Plasminogênio/metabolismo , Pessoa de Meia-Idade , Adulto , Falência Renal Crônica/urina , Estudos de Coortes , Glomerulosclerose Segmentar e Focal/urina , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulonefrite por IGA/urina , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite Membranosa/urina , Glomerulonefrite Membranosa/diagnóstico , Fibrinolisina/urina , Fibrinolisina/metabolismo
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