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1.
J Investig Med High Impact Case Rep ; 10: 23247096221086451, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35491847

RESUMO

Kidney involvement with hepatitis B virus is varied and mostly limited to nephrotic syndrome with membranous nephropathy and nephritic syndrome with membranous proliferative glomerulonephritis. Lupus nephritis is associated with nephritic or nephrotic range proteinuria with most common finding of sub-endothelial electron-dense deposits and immunological stain demonstrating full-house picture with all immunological marker staining. Our case discusses a young male patient presenting with rapidly worsening renal function along with proteinuria, found to be positive for both hepatitis B core antibody along with hepatitis B surface antibody plus positive anti-neutrophilic antibody but negative anti-double-stranded DNA. Kidney biopsy demonstrated hepatitis B-associated lupus-like glomerulonephritis. He responded successfully with antiretroviral therapy and high-dose prednisone. Patient did not need lupus-specific treatment and recovered with antiretroviral therapy only. Hepatitis B-associated lupus-like glomerulonephritis has rarely been reported and possess a diagnostic and therapeutic challenge to all nephrologists.


Assuntos
Glomerulonefrite Membranosa , Glomerulonefrite , Hepatite B , Nefrite Lúpica , Antirretrovirais/uso terapêutico , Feminino , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/etiologia , Glomerulonefrite/patologia , Hepatite B/complicações , Hepatite B/tratamento farmacológico , Humanos , Nefrite Lúpica/complicações , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Masculino , Prednisona/uso terapêutico , Proteinúria/etiologia
2.
Ren Fail ; 44(1): 714-723, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35491890

RESUMO

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) is the fulminant glomerular diseases with poor renal prognosis. Activation of the complement system has recently been reported in the pathogenesis of AAGN, but it remains to be clarified as to which complement pathway is mainly involved. METHODS: 20 patients with myeloperoxidase (MPO)-AAGN were retrospectively evaluated. Using serum samples, circulating immune-complexes (CICs) were assessed by the monoclonal rheumatoid factor assay, and C5a and C5b-9 were assessed by ELISA. Complement activation through the classical pathway was further evaluated by the WIESLAB® Complement System Classical Pathway kit. The affinities of ANCAs were evaluated by a competitive inhibition method using ELISA, and were classified into the high, and low-affinity group. Deposition of complement components, such as C3, C5, C4d, C5b-9, factor Bb, mannan-binding lectin serine peptidase (MASP)-1, MASP-2, and mannose/mannan-binding lectin (MBL), in frozen renal sections were analyzed by immunofluorescence staining. RESULTS: CICs were found to be positive in 65% of the patients. All CIC-positive patients belonged to the high-affinity group. Furthermore, serum C5a and C5b-9 were significantly increased in MPO-AAGN patients, and these levels positively correlated with CIC levels. A significant negative correlation was also found between levels of WIESLAB® classical pathway kit and CICs. By immunofluorescence staining, glomerular deposition of C4d, C5, and C5b-9 were observed in similar distributions in MPO-AAGN patients, whereas the deposition of MASP-1, MASP-2, MBL, and factor Bb were minimal. CONCLUSIONS: These results suggest the involvement of immune-complex induced complement activation through the classical pathway in the pathogenesis of MPO-AAGN.


Assuntos
Glomerulonefrite , Lectina de Ligação a Manose , Anticorpos Anticitoplasma de Neutrófilos , Ativação do Complemento , Complexo de Ataque à Membrana do Sistema Complemento , Feminino , Glomerulonefrite/patologia , Humanos , Masculino , Lectina de Ligação a Manose/metabolismo , Serina Proteases Associadas a Proteína de Ligação a Manose/metabolismo , Peroxidase , Estudos Retrospectivos
3.
Molecules ; 27(7)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35408711

RESUMO

Biospectroscopy offers the ability to simultaneously identify key biochemical changes in tissue associated with a given pathological state to facilitate biomarker extraction and automated detection of key lesions. Herein, we evaluated the application of machine learning in conjunction with Raman spectroscopy as an innovative low-cost technique for the automated computational detection of disease activity in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAGN). Consecutive patients with active AAGN and those in disease remission were recruited from a single UK centre. In those with active disease, renal biopsy samples were collected together with a paired urine sample. Urine samples were collected immediately prior to biopsy. Amongst those in remission at the time of recruitment, archived renal tissue samples representative of biopsies taken during an active disease period were obtained. In total, twenty-eight tissue samples were included in the analysis. Following supervised classification according to recorded histological data, spectral data from unstained tissue samples were able to discriminate disease activity with a high degree of accuracy on blind predictive modelling: F-score 95% for >25% interstitial fibrosis and tubular atrophy (sensitivity 100%, specificity 90%, area under ROC 0.98), 100% for necrotising glomerular lesions (sensitivity 100%, specificity 100%, area under ROC 1) and 100% for interstitial infiltrate (sensitivity 100%, specificity 100%, area under ROC 0.97). Corresponding spectrochemical changes in paired urine samples were limited. Future larger study is required, inclusive of assigned variables according to novel non-invasive biomarkers as well as the application of forward feature extraction algorithms to predict clinical outcomes based on spectral features.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Nefropatias , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/urina , Anticorpos Anticitoplasma de Neutrófilos , Biomarcadores/urina , Biópsia , Glomerulonefrite/diagnóstico , Glomerulonefrite/patologia , Humanos , Rim/patologia , Nefropatias/patologia , Projetos Piloto , Análise Espectral Raman
4.
Lancet ; 399(10335): 1646-1663, 2022 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-35461559

RESUMO

Glomerulonephritis is a heterogeneous group of disorders that present with a combination of haematuria, proteinuria, hypertension, and reduction in kidney function to a variable degree. Acute presentation with full blown nephritic syndrome or rapidly progressive glomerulonephritis is uncommon and is mainly restricted to patients with post-infectious glomerulonephritis, anti-neutrophil cytoplasmic antibodies-associated vasculitis, and anti-glomerular basement membrane disease. Most frequently, patients present with asymptomatic haematuria and proteinuria with or without reduced kidney function. All glomerulonephritis disorders can show periods of exacerbation, but disease flairs characteristically occur in patients with IgA nephropathy or C3 glomerulopathy. The gold standard for the diagnosis of a glomerulonephritis is a kidney biopsy, with a hallmark glomerular inflammation that translates into various histopathological patterns depending on the location and severity of the glomerular injury. Traditionally, glomerulonephritis was classified on the basis of the different histopathological patterns of injury. In the last few years, substantial progress has been made in unravelling the underlying causes and pathogenetic mechanisms of glomerulonephritis and a causal approach to the classification of glomerulonephritis is now favoured over a pattern-based approach. As such, glomerulonephritis can be broadly classified as immune-complex glomerulonephritis (including infection-related glomerulonephritis, IgA nephropathy, lupus nephritis, and cryoglobulinaemic glomerulonephritis), anti-neutrophil cytoplasmic antibodies-associated (pauci-immune) glomerulonephritis, anti-glomerular basement membrane glomerulonephritis, C3 glomerulopathy, and monoclonal immunoglobulin-associated glomerulonephritis. We provide an overview of the clinical presentation, pathology, and the current therapeutic approach of the main representative disorders in the spectrum of glomerulonephritis.


Assuntos
Glomerulonefrite por IGA , Glomerulonefrite , Anticorpos Anticitoplasma de Neutrófilos/análise , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Biópsia/efeitos adversos , Feminino , Glomerulonefrite/patologia , Hematúria/etiologia , Humanos , Masculino , Proteinúria/complicações
5.
Front Immunol ; 13: 834878, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392077

RESUMO

Introduction: The "Renal Risk Score" (RRS) and the histopathological classification have been proposed to predict the risk of end-stage kidney disease (ESKD) in ANCA-associated glomerulonephritis (ANCA-GN). Besides, factors associated with kidney function recovery after ANCA-GN onset remain to be more extensively studied. In the present study, we analyzed the value of the RRS and of the histopathological classification for ESKD prediction. Next, we analyzed factors associated with eGFR change within the first 2 years following ANCA-GN diagnosis. Materials and Methods: We included patients from the Maine-Anjou ANCA-associated vasculitis registry with at least 6 months of follow-up. The values of ANCA-GN, histopathological classification, and RRS, and the factors associated with eGFR variations between ANCA-GN diagnosis and 2 years of follow-up were assessed. Results: The predictive values of the histopathological classification and RRS were analyzed in 123 patients. After a median follow-up of 42 months, 33.3% patients developed ESKD. The predictive value of RRS for ESKD was greater than that of the histopathological classification. Determinants of eGFR variation were assessed in 80/123 patients with complete eGFR measurement. The median eGFR increased from ANCA-GN diagnosis to month 6 and stabilized thereafter. The only factor associated with eGFR variation in our study was eGFR at ANCA-GN diagnosis, with higher eGFR at diagnosis being associated with eGFR loss (p<0.001). Conclusion: The RRS has a better predictive value for ESKD than the histopathological classification. The main determinant of eGFR variation at 2 years was eGFR at ANCA-GN diagnosis. Thus, this study suggests that eGFR recovery is poorly predicted by histological damage at ANCA-GN diagnosis.


Assuntos
Glomerulonefrite , Falência Renal Crônica , Anticorpos Anticitoplasma de Neutrófilos/análise , Biópsia , Glomerulonefrite/patologia , Humanos , Rim/patologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Falência Renal Crônica/patologia , Estudos Retrospectivos , Fatores de Risco
6.
Iran J Kidney Dis ; 1(1): 63-65, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35271501

RESUMO

Crescentic IgA nephropathy (IgAN) with the positivity for antineutrophilic cytoplasmic antibody (ANCA) is a novel and uncommon entity. The optimal management of this condition is not well-defined. We report a 49-years-old woman with complaints of skin rash and swelling of lower limbs. She had hematuria, proteinuria and, progressive renal impairment with positive myeloperoxidase (MPO)-ANCA test. A renal biopsy revealed MPO-ANCA-associated crescentic IgAN. Induction therapy was intravenous methylprednisolone, cyclophosphamide and, therapeutic plasma exchange (TPE). An unexpected disease flare-up was observed during induction immunosuppressive therapy which regressed after long-term TPE. The patient experienced a full renal recovery after treatment with long-term TPE, cyclophosphamide, and corticosteroids.  DOI: 10.52547/ijkd.6490.


Assuntos
Glomerulonefrite por IGA , Glomerulonefrite , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Ciclofosfamida/uso terapêutico , Feminino , Glomerulonefrite/patologia , Glomerulonefrite/terapia , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Peroxidase/uso terapêutico , Troca Plasmática
7.
Front Immunol ; 13: 831253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35309370

RESUMO

We previously showed that the rupture of Bowman's capsule (BC) promotes the progression of crescentic glomerulonephritis by enhancing the entry of CD8+ T cells into the glomeruli. In the present study, we utilized digital spatial profiling to simultaneously profile the altered abundances of the messenger RNA (mRNA) transcripts and proteins in the glomerular and periglomerular areas of four biopsy samples of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis (ANCA-GN) and two biopsy specimens of minimal change disease (MCD) controls. The paraffin-embedded biopsy samples were stained with collagen IV, CD45, and SYTO 13 to distinguish the glomeruli with periglomerular infiltration but intact BC, with focal BC rupture, and with extensive rupture of BC and glomeruli without crescent formation and leukocytic infiltration in ANCA-GN. By assessing multiple discrete glomerular areas, we found that the transcript expression levels of the secreted phosphoprotein-1 and its receptor CD44 were upregulated significantly in the glomeruli with more severe ruptures of BC, and their expression levels correlated positively with the fibrotic markers. We also found that both alternative and classic complement pathways were activated in the glomeruli from patients with ANCA-GN. Furthermore, M1 macrophages were involved mostly in the early stage of BC rupture, while M2 macrophages were involved in the late stage and may contribute to the fibrosis process of the crescents. Finally, loss of glomerular cells in ANCA-GN was likely mediated by apoptosis. Our results show that digital spatial profiling allows the comparative analysis of the mRNA and protein profiles in individual glomeruli affected differently by the disease process and the identification of potential novel mechanisms in ANCA-GN.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos , Glomerulonefrite , Anticorpos Anticitoplasma de Neutrófilos/análise , Autoanticorpos , Linfócitos T CD8-Positivos/metabolismo , Feminino , Glomerulonefrite/patologia , Humanos , Glomérulos Renais/patologia , Masculino , RNA Mensageiro
8.
Cell Commun Signal ; 20(1): 28, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264186

RESUMO

BACKGROUND: Mesenchymal stem cells (MSCs) and their released extracellular vesicles (Evs) have shown protective effects against kidney diseases. This study aims to study the functions of umbilical cord MSCs-released Evs (ucMSC-Evs) and their implicated molecules in mesangial proliferative glomerulonephritis (MsPGN). METHODS: A rat model of MsPGN was induced by anti-Thy-1.1, and rat mesangial cells (rMCs) HBZY-1 were treated with PDGF-BB/DD to mimic MsPGN condition in vitro. Rats and cells were treated with different doses of ucMSC-Evs, and then the pathological changes in renal tissues and proliferation of rMCs were determined. Differentially expressed microRNAs (miRNAs) after Evs treatment were screened by microarray analysis. The interactions among miR-378, PSMD14, and TGFBR1 were analyzed. Gain- and loss-of function studies of miR-378 and PSMD14 were performed to explore their effects on tissue hyperplasia and rMC proliferation and their interactions with the TGF-ß1/Smad2/3 signaling pathway. RESULTS: The ucMSC-Evs treatment ameliorated mesangial hyperplasia and fibrosis in rat renal tissues and suppressed the aberrant proliferation of rMCs in a dose-dependent manner. miR-378 was the most upregulated miRNA in tissues and cells after ucMSC-Evs treatment. miR-378 directly targeted PSMD14, and PSMD14 maintained the stability of TGFBR1 through deubiquitination modification, which led to TGF-ß1/Smad2/3 activation. Either miR-378 knockdown or PSMD14 overexpression diminished the protective functions of ucMSC-Evs by activating the TGF-ß1/Smad2/3 signaling pathway. CONCLUSION: UcMSC-Evs ameliorate pathological process in MsPGN through the delivery of miR-378, which suppresses PSMD14-mediated TGFBR1 stability and inactivates the TGF-ß1/Smad2/3 signaling pathway to reduce tissue hyperplasia and rMC proliferation. Video abstract.


Assuntos
Vesículas Extracelulares , Glomerulonefrite , Células-Tronco Mesenquimais , MicroRNAs , Animais , Vesículas Extracelulares/metabolismo , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Hiperplasia/metabolismo , Hiperplasia/patologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ratos , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Transativadores/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Cordão Umbilical/citologia
9.
Clin Nephrol ; 97(5): 289-297, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35142282

RESUMO

Billions of COVID-19 vaccine doses have been administered to combat the ongoing global pandemic caused by severe acute respiratory syndrome coronavirus-2. While these vaccines are considered safe, with most adverse events being mild to moderate and transient, uncommon systemic side effects of the vaccines, including de novo or re-activation of various glomerular diseases have recently been observed. We report 6 patients who developed glomerular or acute tubulointerstitial disease shortly after receiving COVID-19 vaccinations. Five of these patients received mRNA vaccines (3 Moderna, 2 Pfizer-BioNTech) and 1 received adenovirus-26 vector vaccine (Johnson and Johnson/Janssen). Four of our patients developed de novo glomerulonephritis or acute tubulointerstitial nephritis (ATIN), while the other 2 had re-activation of prior glomerulonephritis. Two patients presented with acute kidney injury (AKI) characterized by severe ATIN. While both of them also had evidence of immune complex glomerular disease, ATIN was the dominant feature on the biopsies. Two other patients presented with high-grade proteinuria and AKI. Like the aforementioned patients, these patients had evidence of immune complex glomerular disease, but acute onset nephrotic syndrome was the leading clinical feature. Another patient presented with de novo myeloperoxidase-anti-neutrophil-cytoplasmic-antibody-associated pauci-immune crescentic glomerulonephritis. Yet another patient had re-activation of immunoglobulin-A glomerulonephritis that had been quiescent for several years prior to the vaccination. It is difficult to ascertain any causal relationship between COVID-19 vaccination and onset/recurrence of kidney diseases. However, vigilance about occurrence of such complications is imperative. Importantly, all our cases responded well to the immunosuppressive treatment.


Assuntos
Injúria Renal Aguda , COVID-19 , Glomerulonefrite , Injúria Renal Aguda/etiologia , Complexo Antígeno-Anticorpo , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Glomerulonefrite/patologia , Humanos , Masculino , Nefrite Intersticial , Vacinação
10.
Am J Nephrol ; 53(2-3): 199-206, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35168235

RESUMO

INTRODUCTION: Opisthorchis viverrini (OV) is a major cause of infection in Southeast Asia. Previous studies in mouse models have shown that OV infection can contribute to immune-complex glomerulonephritis (GN). However, OV infection in human kidney tissue has never been demonstrated. Herein, we evaluated the association of OV infection with biopsy-proven glomerular disease. METHODS: This study was performed in adult patients who underwent kidney biopsy between July 2016 and February 2017. All kidney tissue samples were processed using the standard techniques for renal pathological diagnoses and immunohistochemistry techniques to detect OV antigen. Pre-implanted donor kidney tissue samples were used as controls. The participants were also assessed for OV infection by serum OV immunoglobulin G antibody (Ab) levels and/or presence of OV eggs in stool. RESULTS: Forty-three renal tissue samples from glomerular disease patients and 50 from transplant donors were included in the study. Mean age in the GN group was 41.7 ± 15.9 years, estimated glomerular filtration rate (eGFR) was 70.65 ± 36.61 mL/min/1.73 m2, and median proteinuria was 3.17 (1.70-4.95) g/day. Lupus nephritis (LN) was the most common diagnosis (32.6%), followed by IgA nephropathy (23.3%), IgM nephropathy (18.6%), and primary membranous nephropathy (MN; 7%). The OV antigen was observed in kidney tissue from patients with IgA nephropathy, LN, primary MN, focal segmental glomerulosclerosis, and IgM nephropathy. By contrast, no OV antigen was detected in tissue samples from the control group. The presence of OV antigens was observed in glomerular endothelial cells, mesangial cells, tubular cells, and peritubular capillaries. The odds ratio of positive serum OV Ab to predict the presence of OV antigen in kidney tissues was 4.47 (p = 0.057), and there was a negative correlation between levels of serum OV Ab and eGFR (r = -0.31, p = 0.04). DISCUSSION/CONCLUSION: This is the first study to demonstrate the presence of OV antigen in human kidney tissue, which indicates that OV infection may be associated with biopsy-proven glomerular diseases.


Assuntos
Glomerulonefrite por IGA , Glomerulonefrite , Opistorquíase , Animais , Biópsia , Células Endoteliais/patologia , Glomerulonefrite/complicações , Glomerulonefrite/epidemiologia , Glomerulonefrite/patologia , Glomerulonefrite por IGA/patologia , Humanos , Rim/patologia , Camundongos , Opistorquíase/complicações , Opistorquíase/diagnóstico , Opistorquíase/epidemiologia , Tailândia/epidemiologia
11.
BMC Nephrol ; 23(1): 56, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-35123445

RESUMO

BACKGROUND: To date, a few case reports have described the association between poststreptococcal acute glomerulonephritis (PSAGN) and hemolytic anemia/thrombocytopenia, both with or without a pathology similar to that of thrombotic microangiopathy (TMA). However, the detailed mechanism leading to the complication of TMA in PSAGN patients remains to be clarified. In contrast, infection with neuraminidase-producing Streptococcus pneumoniae is a well-known cause of TMA, and it has been reported that transient positivity of the direct Coombs test is observed in up to 90% of such patients. CASE PRESENTATION: A 44-year-old man was hospitalized for acute nephritic syndrome 3 weeks after developing pharyngitis. PSAGN was suspected owing to a low complement C3, increased antistreptolysin-O and serum creatinine (5.46 mg/dL), and hematuria/proteinuria. The throat antigen test for group A Streptococcus was positive. He developed hemolytic anemia with thrombocytopenia from hospital day 9. TMA was suspected owing to minimal coagulation abnormalities. ADAMTS-13 activity was normal, whereas the direct Coombs test was transiently positive. Renal biopsy demonstrated glomerular endocapillary proliferation without crescents, but with severe tubulitis and peritubular capillaritis on light microscopy. Immunofluorescence demonstrated C3 deposition along the glomerular capillary walls, and many subepithelial humps were observed on electron microscopy. The deposition of nephritis-associated plasmin receptor (NAPlr), a nephritogenic protein of Streptococcus pyogenes, was observed only in glomeruli. Thus, the histological diagnosis was typical PSAGN, but with atypical severe tubulointerstitial lesions. A positive direct Coombs test is often observed in pneumococcal TMA patients, which is attributed to the exposure of Thomsen-Friedenreich (T) antigen by neuraminidase. As Streptococcus pyogenes is one of the neuraminidase-producing bacteria other than Streptococcus pneumoniae, T-antigen exposure was analyzed in the renal tissue of this patient using labelled peanut lectin as a probe, which has strong and specific binding affinity for T-antigen. Exposure of T-antigen was found on tubular epithelial cells and small vessels in the tubulointerstitial area, but not in the glomeruli of this patient. CONCLUSION: These findings suggest that 2 pathogenic proteins of Streptococcus pyogenes, i.e., NAPlr and neuraminidase, induced glomerular lesions of PSAGN and tubulointerstitial inflammation with TMA, respectively, resulting in severe acute kidney injury in this patient.


Assuntos
Glomerulonefrite/complicações , Infecções Estreptocócicas/complicações , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Adulto , Teste de Coombs , Glomerulonefrite/microbiologia , Glomerulonefrite/patologia , Humanos , Masculino , Streptococcus pyogenes
12.
Indian J Pathol Microbiol ; 65(1): 59-64, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35074967

RESUMO

BACKGROUND: The spectrum of kidney diseases varies in the elderly population with frequent inconsistencies between clinical presentation and histopathological diagnosis. The immunofluorescence (IF) may provide additional information in such situations. AIMS: The purpose was to study the spectrum of kidney diseases in patients above 50 years undergoing renal biopsy and utility of light chain (LC) IF in the diagnosis. SETTINGS AND DESIGN: This was a retrospective, crosssectional, singlecenter-based study. MATERIAL AND METHODS: The clinical details, histopathological findings, and LC IF pattern in native renal biopsy of patients above 50 years were noted. STATISTICAL ANALYSIS: Continuous variables were presented as mean ± standard deviation (SD). Categorical variables were expressed as frequencies and percentages. RESULTS: A total of 205 patients were included in the study. The most common clinical presentation was acute kidney injury/rapidly progressive glomerulonephritis (AKI/RPGN) (49%). Glomerular diseases (72%) were more common. Crescentic glomerulonephritis (21%) and membranous nephropathy (MN) (19%) were the most common glomerulopathy. LC restriction was observed in LC cast nephropathy (LCCN), primary amyloidosis, and LC also helped in classifying the cases of MPGN-type morphology. CONCLUSIONS: AKI/RPGN was the most common indication for renal biopsy in patients above 50 years. Crescentic GN and MN were the frequent glomerular pathology. LC IF is a useful adjunctive tool to classify various renal diseases.


Assuntos
Imunofluorescência/métodos , Nefropatias/classificação , Nefropatias/patologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/patologia , Fatores Etários , Idoso , Biópsia , Estudos Transversais , Feminino , Glomerulonefrite/patologia , Humanos , Rim/patologia , Nefropatias/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
13.
Matrix Biol ; 106: 12-33, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35032611

RESUMO

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are severe inflammatory disorders that often involve focal necrotizing glomerulonephritis (FNGN) and consequent glomerular scarring, interstitial fibrosis, and chronic kidney disease. Robust murine models of scarring in FNGN that may help to further our understanding of deleterious processes are still lacking. Here, we present a murine model of severe FNGN based on combined administration of antibodies against the glomerular basement membrane (GBM) and myeloperoxidase (MPO), and bacterial lipopolysaccharides (LPS), that recapitulates acute injury and was adapted to investigate subsequent glomerular and interstitial scarring. Hematuria without involvement of other organs occurs consistently and rapidly, glomerular necrosis and crescent formation are evident at 12 days, and consequent glomerular and interstitial scarring at 29 days after initial treatment. Using mass-spectrometric proteome analysis, we provide a detailed overview of matrisomal and cellular changes in our model. We observed increased expression of the matrisome including collagens, fibronectin, tenascin-C, in accordance with human AAV as deduced from analysis of gene expression microarrays and tissue staining. Moreover, we observed tissue infiltration by neutrophils, macrophages, T cells and myofibroblasts upon injury. Experimental inhibition of CXCR4 using AMD3100 led to a sustained histological presence of fibrin extravasate, reduced chemokine expression and leukocyte activation, but did not markedly affect ECM composition. Altogether, we demonstrate an adapted FNGN model that enables the study of matrisomal changes both in disease and upon intervention, as exemplified via CXCR4 inhibition.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Glomerulonefrite , Receptores CXCR4 , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/genética , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/metabolismo , Anticorpos Anticitoplasma de Neutrófilos , Membrana Basal Glomerular/metabolismo , Glomerulonefrite/genética , Glomerulonefrite/patologia , Humanos , Camundongos , Peroxidase/genética , Peroxidase/metabolismo , Receptores CXCR4/antagonistas & inibidores , Receptores CXCR4/genética , Receptores CXCR4/metabolismo
14.
Nephrology (Carlton) ; 27(4): 307-317, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34676611

RESUMO

Immunoglobulin A nephropathy is the main cause of glomerulonephritis globally and an important aetiology of end-stage renal disease in children. It has been considered an autoimmune disease that can lead to the production of autoantibodies against abnormal IgA1 and formation of immune complexes. These autoantibodies and immune complexes deposit in the glomeruli, resulting in renal injury. At the beginning of IgA nephropathy course, most patients are asymptomatic and the first clinical manifestations in children are macroscopic hematuria and proteinuria. The diagnosis is defined by the detection of IgA mesangial deposits in kidney biopsy using immunofluorescence techniques. The Oxford MEST-C score is the most used classification to associate histological findings and clinical outcomes, being validated for application in children. Recommended treatment options are antihypertensive and antiproteinuric therapy, corticosteroids, immunosuppressive agents, and other non-pharmacological approaches. There is no ideal prognosis indicator but new perspectives are in science's scope to find possible biomarkers of the disease through OMICS's research. This review aims to summarize and to up-to-date the scientific literature on paediatric IgA nephropathy, focusing on pathophysiology, clinical findings, histopathology, current treatment, prognosis, and future perspectives.


Assuntos
Glomerulonefrite por IGA , Glomerulonefrite , Pediatria , Criança , Glomerulonefrite/patologia , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/terapia , Humanos , Imunoglobulina A , Glomérulos Renais/patologia
15.
Intern Med ; 61(8): 1201-1204, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-34565773

RESUMO

A 64-year-old Japanese man who worked at a butcher shop was hospitalized for a fever, headache, and deafness. We diagnosed him with sepsis and meningitis caused by Streptococcus suis infection. The patient's renal function declined rapidly, and hemodialysis was performed temporarily. A renal biopsy was performed, and the renal function tended to improve with antimicrobial therapy. This case seemed rather similar to one of staphylococcal-associated nephritis in that it showed mesangial proliferative nephritis with immunoglobulin A deposition, even though the nephritis was caused by streptococci. Similarly, intramembranous electron-dense deposits were characteristic findings. We present new findings of an in vivo renal biopsy in a case of S. suis-associated glomerulonephritis.


Assuntos
Glomerulonefrite , Nefrite , Streptococcus suis , Biópsia , Feminino , Glomerulonefrite/complicações , Glomerulonefrite/patologia , Humanos , Masculino , Pessoa de Meia-Idade
16.
Int Urol Nephrol ; 54(2): 365-376, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33991297

RESUMO

PURPOSE: The aim of this retrospective study was: to analyze the epidemiological patterns of the kidney disease based on clinical and histological features in a single-center in the N-E region of Romania, between 2011 and 2019 and to compare the biopsy results with the others periods, as well as the results from other countries. METHODS: We studied 442 renal biopsies. The indications for renal biopsy were represented by the clinical features: nephrotic syndrome, nephritic syndrome, asymptomatic urinary abnormalities, acute kidney injury, and chronic kidney disease of unknown etiology. RESULTS: During the past 8 years, the annual incidence of renal biopsies was constant, albeit this incidence remained lower than in other countries. Nephrotic syndrome was the most common indication for renal biopsy (47.6%). Primary glomerulonephritis (GN) was the most common diagnosis in each of the three periods, followed by secondary GN. Vascular nephropathy and TIN were constant as a proportion from the overall biopsies in each of the three periods. The membranoproliferative GN (24.4%) and membranous nephropathy (MN) (21.9%) were the most prevalent primary GN, while lupus nephritis (LN) was the most common secondary glomerular disease in young female patients (7.5%). Compared to 1994-2004 period, we observed a significant decrease of incidence of focal segmental glomerulosclerosis (FSGS) and mesangial proliferative GN, and a significant increases in the frequency of MN. CONCLUSION: The results of this study show that the GN distribution model was constant in N-E Romania and became similar to that observed in many countries with high socio-economic status.


Assuntos
Glomerulonefrite/epidemiologia , Glomerulonefrite/patologia , Rim/patologia , Adulto , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Romênia/epidemiologia , Fatores de Tempo
18.
Int Urol Nephrol ; 54(5): 1091-1096, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34398345

RESUMO

PURPOSE: Cytomegalovirus infection is an important complication in immunocompromised patients. As few studies have shown that cyclophosphamide treatment is a risk factor for cytomegalovirus infection in patients with glomerulonephritis, we aimed to describe the frequency and risk factors of cytomegalovirus infection in glomerulonephritis patients treated with cyclophosphamide. METHODS: We prospectively recruited 43 cytomegalovirus seropositive patients with glomerulonephritis treated with cyclophosphamide. We screened all patients for viral DNA monthly during treatment. Patients were compared for age, sex, glomerular pathology, renal function and clinical status regarding development of cytomegalovirus infection before and after the treatment. RESULTS: Cytomegalovirus infection was detected in 10 (23.3%) patients, most commonly within the first 2 months of cyclophosphamide treatment. All patients recovered without any cytomegalovirus-related complications. Patients with cytomegalovirus infection had higher serum creatinine (4.2 ± 3.2 vs. 1.9 ± 1.8 mg/dl, p = 0.006) and lower estimated glomerular filtration rate (29 ± 11 vs. 65 ± 8 ml/min/1.73 m2, p = 0.016) at diagnosis compared with cytomegalovirus infection non-occurred patients. In addition, number of patients presented with rapidly progressive glomerulonephritis were higher in cytomegalovirus infection group (80.0% vs. 27.3%, p = 0.007). Moreover, cytomegalovirus infection was associated with prolonged hospital stay (54 ± 7 vs. 29 ± 6 days, p = 0.027). CONCLUSION: Cytomegalovirus infection is a common complication in glomerulonephritis patients treated with cyclophosphamide in this prospective study. Routine monitoring and prophylaxis should be considered for these high-risk patients.


Assuntos
Infecções por Citomegalovirus , Glomerulonefrite , Ciclofosfamida/efeitos adversos , Infecções por Citomegalovirus/induzido quimicamente , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológico , Glomerulonefrite/complicações , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/patologia , Humanos , Imunossupressores/efeitos adversos , Estudos Prospectivos
19.
Pediatr Nephrol ; 37(3): 593-600, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34453602

RESUMO

BACKGROUND: IgA-dominant infection-associated glomerulonephritis is well-documented in adults but has not been studied in depth in children. We assessed the incidence of pediatric IgA-dominant infection-associated glomerulonephritis and clinical and kidney biopsy findings. METHODS: Pediatric native kidney biopsies over a 10-year period with IgA dominance, strong C3, and findings indicative of infection-associated etiology were identified. RESULTS: We identified 9 cases of IgA-dominant infection-associated glomerulonephritis, 0.8% of pediatric native kidney biopsies. Seven patients presented with elevated creatinine. All had hematuria and proteinuria. Eight patients had clinical evidence of infection: one each with central port infection by methicillin-sensitive Staphylococcus aureus, recurrent streptococcal pharyngitis and recent otitis media, streptococcal pharyngitis demonstrated 8 months after biopsy, suspected streptococcal scalded skin syndrome, and viral gastroenteritis, and three with serologic evidence of Streptococcal infection but no identified site of infection. All but one patient experienced short-term normalization of creatinine and resolution of proteinuria, though two eventually progressed to kidney failure: one 3 years later due to progressive disease and one 11 years later due to focal segmental glomerulosclerosis without concurrent immune deposits. CONCLUSIONS: Pediatric IgA-dominant infection-associated glomerulonephritis is rare, and generally has a favorable prognosis, contrasting that seen in adults with severe comorbidities. A higher resolution version of the Graphical abstract is available as Supplementary.


Assuntos
Glomerulonefrite por IGA , Glomerulonefrite , Faringite , Adulto , Criança , Creatinina , Feminino , Glomerulonefrite/complicações , Glomerulonefrite/patologia , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/patologia , Humanos , Imunoglobulina A , Masculino , Proteinúria/etiologia
20.
Adv Clin Exp Med ; 31(3): 249-259, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34898058

RESUMO

BACKGROUND: The WNT signaling pathway contributes to renal fibrosis, which is a hallmark of chronic kidney disease (CKD). Serum concentration of WNT4 could be used to monitor the kidney disease; however, no data have yet been published on the subject. OBJECTIVES: This study measures WNT4 protein in serum of CKD patients depending on the stage, type of nephropathy, the non-nephrotic (NNP) or nephrotic proteinuria (NP), inflammatory cell infiltration in kidney parenchyma (IIKP), interstitial fibrosis in biopsy and serum creatinine. We also evaluated the usefulness of the serum WNT4 as a marker of fibrosis and IIKP. MATERIAL AND METHODS: The WNT4 protein level in serum of CKD patients and healthy individuals was measured using enzyme-linked immunoassay (ELISA). Patients' blood biochemical profiles and kidney biopsies were evaluated with common laboratory methods. RESULTS: The serum level of WNT4 protein was higher in CKD patients (i) regardless of the underlying etiology and at early stages of disease; (ii) with lupus nephritis and Immunoglobulin A (IgA) nephropathy; (iii) without or with a small area of IIKP; and (iv) with a small area covered with fibrosis. No difference was observed between NNP and NP patients. The utility of serum WNT4 as a marker of IIKP and fibrosis was not confirmed. Negative correlations with total and low-density lipoprotein (LDL)-cholesterol were found in CKD and IIKP patients. In patients with serum WNT4 above the median value, serum creatinine was higher. However, no correlation between serum WNT4 and creatinine level was found. CONCLUSIONS: The observed increase in serum WNT4 protein in the early stages of CKD and in patients diagnosed with immune-mediated glomerular disease may suggest that WNT4 may act as a mediator of inflammation. A certain association with the dysregulation of serum lipid metabolism can also be suspected. Serum WNT4 protein may be considered as the indicator of chronic glomerulonephritis, but not a diagnostic marker of IIKP and fibrosis.


Assuntos
Glomerulonefrite por IGA , Glomerulonefrite , Fibrose , Glomerulonefrite/complicações , Glomerulonefrite/patologia , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/patologia , Humanos , Rim/patologia , Proteína Wnt4
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