Hereditary and acquired complement dysregulation in membranoproliferative glomerulonephritis

2009 ◽  
Vol 101 (02) ◽  
pp. 271-278 ◽  
Author(s):  
Veronique Fremeaux-Bacchi ◽  
Christoph Licht
Keyword(s):  
Membranoproliferative Glomerulonephritis ◽  
Age Of Onset ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Disease Recurrence ◽  
C3 Nephritic Factor ◽  
Dense Deposit ◽  
Glomerular Deposits ◽  
End Stage

SummaryMembranoproliferative glomerulonephritis (MPGN) is a chronic progressive renal disease that is diagnosed on the basis of renal histological features. Several MPGN subtypes have been defined by the localization and composition of glomerular deposits (electron dense, Ig and C3). MPGN II or dense deposit disease (DDD) which is defined by the occurrence of electron dense deposits within the lamina densa of the glomerular basement membrane (GBM) is strongly associated with dysregulation of the alternative complement pathway (AP). However, C3 Nephritic Factor (C3NeF), an autoantibody against the alternative C3 convertase C3bBb, and mutations in regulatory proteins of the AP have also been identified in other subtypes of MPGN and even in glomerulonephritis with mesangial C3 deposits. Clinically, MPGN is characterized by proteinuria (up to nephrotic range) and hypertension, frequent progression to end-stage kidney disease and disease recurrence after renal transplantation. The age of onset varies from childhood to adulthood. In the following we will review our current knowledge of pathogenesis of MPGN and will present a novel classification system of the disease based on pathogenesis rather than on morphology. A better understanding of the pathogenesis of MPGN is crucial for the development of novel, specific treatment strategies.

scholarly journals Membranoproliferative glomerulonephritis with C3 and intramembranous dense deposits

2013 ◽  
Vol 19 (S4) ◽  
pp. 43-44
Author(s):  
F. Carvalho ◽  
H. Viana ◽  
A.P. Alves de Matos ◽  
M. Amoedo
Keyword(s):  
Basement Membrane ◽  
Membranoproliferative Glomerulonephritis ◽  
Correct Diagnosis ◽  
Type I ◽  
Type Ii ◽  
C3 Nephritic Factor ◽  
Dense Deposit ◽  
Dense Deposits ◽  
Capillary Walls ◽  
Mild Renal Insufficiency

Membranoproliferative glomerulonephritis (MPGN) encompasses 7 to 10% of all biopsied glomerulonephritis. They are divided in: MPGN type I; MPGN type II and MPGN type III, being primary or secondary. MPGN type I are the most frequent, MPGN types II and III are very rare and difficult to diagnose without clinical and morphologic findings integration. MPGN type II or Dense Deposit Disease has a varied morphologic appearance with a few numbers of cases showing a membranoproliferative pattern by Light microscopy (LM). Electron microscopy (EM) is pivotal to confirm the diagnosis.We present a case of 35 years old man, with nephrotic proteinuria and mild renal insufficiency since 2 years. The only relevant clinical data is facial lipodystrophy. Complement 3 (C3) was low and C3 nephritic factor negative. There were not other relevant abnormalities. Renal biopsy was fixed in buffered formaldehyde 10% and performed for LM. The frozen fragment, prepared for observation by fluorescence microscopy - immunofluorescence (IMF) -, was prepared to be stained with florescent anti-serums, against immunoglobulines (IgG, IgA and IgM) and complement factors (C3, C4, and C1q). EM was later done on tissue formaldehyde fixed reprocessed from paraffin-embebbed for LM, because there was no tissue fragment fixed in glutaraldehyde.LM showed variable endocapillary hypercelullarity, with neutrophils infiltration. Capillary walls were thickened due to the deposition of elongate and ribbon-like deposits. Few double contours were visible (Figure 1a). IMF demonstrated the presence of C3 deposits in the capillary walls and mesangium (Figure 1b). EM confirmed the presence of an intramembranous dense deposit along basement membrane which was thickened (Figure 1c). LM and IMF findings favored the diagnosis of MPGN type II with C3 deposits and thickening of basement membrane. Nevertheless EM was essential to confirm intramembranous unequivocally dense deposits.MPGN type II is a rare glomerulonephritis mediated by complement deregulation. The integration of clinical and morphologic findings is essential to get a correct diagnosis. In this setting EM is highly distinctive and required for a definitive diagnosis.

scholarly journals Cholemic Nephropathy: Hyperbilirubinemia and its Impact on Renal Function

2019 ◽  
Vol 3 (1) ◽  
pp. 33-39 ◽  
Author(s):  
Jonathan S Chávez-Iñiguez ◽  
Alejandra Meza-Ríos ◽  
Arturo Santos-Garcia ◽  
Guillermo García-García ◽  
Juan Armendáriz-Borunda
Keyword(s):  
Renal Function ◽  
Liver Disease ◽  
Renal Impairment ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Severe Liver Dysfunction ◽  
Proximal Tubulopathy ◽  
End Stage

Cholemic nephropathy represents a spectrum of renal injury, from proximal tubulopathy to intrarenal bile cast formation, found in patients with severe liver dysfunction. It is caused by hyperbilirubinemia, usually in jaundiced patients. Acute kidney injury is one of the most important complications in patients with end-stage liver disease. The relationship between liver disease and renal impairment, especially the effect of hyperbilirubinemia on renal tissue and renal function, has not been fully elucidated. These considerations deem necessary for nephrologists, when performing a clinical evaluation of patients with liver diseases, for the implementation of an integrated medical approach. This review focuses on the current knowledge on cholemic nephropathy with emphasis on the role of hyperbilirubinemia on renal impairment. The treatment strategies and outcome are also discussed.

scholarly journals Long-term outcomes of patients with end-stage kidney disease due to membranoproliferative glomerulonephritis: an ANZDATA registry study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Gregory J. Wilson ◽  
Yeoungjee Cho ◽  
Armando Teixiera-Pinto ◽  
Nicole Isbel ◽  
Scott Campbell ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Kidney Disease ◽  
Membranoproliferative Glomerulonephritis ◽  
Patient Survival ◽  
Disease Recurrence ◽  
Allograft Survival ◽  
End Stage Kidney Disease ◽  
Kidney Replacement Therapy ◽  
Allograft Loss ◽  
End Stage

Abstract Background Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end stage kidney disease (ESKD) and the clinical outcomes of patients with MPGN who commence kidney replacement therapy have not been comprehensively studied. Methods All adult patients with ESKD due to glomerulonephritis commencing kidney replacement therapy in Australia and New Zealand from January 1, 1996 to December 31, 2016 were reviewed. Patients with ESKD due to MPGN were compared to patients with other forms of glomerulonephritis. Patient survival on dialysis and following kidney transplantation, kidney recovery on dialysis, time to transplantation, allograft survival, death-censored allograft survival and disease recurrence post-transplant were compared between the two groups using Kaplan Meier survival curves and Cox proportional hazards regression. Results Of 56,481 patients included, 456 (0.8%) had MPGN and 12,660 (22.4%) had another form of glomerulonephritis. Five-year patient survival on dialysis and following kidney transplantation were similar between patients with ESKD from MPGN and other forms of glomerulonephritis (Dialysis: 59% vs. 62% p = 0.61; Transplant: 93% vs. 93%, p = 0.49). Compared to patients with other forms of glomerulonephritis, patients with MPGN had significantly poorer 5-year allograft survival (70% vs. 81% respectively, p = 0.02) and death censored allograft survival (74% vs. 87%, respectively; p < 0.01). The risk of disease recurrence was significantly higher in patients with MPGN compared to patients with other glomerulonephritidites (18% vs. 5%; p < 0.01). In patients with MPGN who had allograft loss, patients with MPGN recurrence had a significantly shorter time to allograft loss compared to patients with MPGN who had allograft loss due to any other cause (median time to allograft loss 3.2 years vs. 4.4 years, p < 0.01). Conclusions Compared with other forms of glomerulonephritis, patients with MPGN experienced comparable rates of survival on dialysis and following kidney transplantation, but significantly higher rates of allograft loss due to disease recurrence.

scholarly journals Gastrointestinal implications in COVID-19

2020 ◽  
Vol 68 (8) ◽  
pp. 1397-1401 ◽  
Author(s):  
Dushyant Singh Dahiya ◽  
Asim Kichloo ◽  
Michael Albosta ◽  
Sukrut Pagad ◽  
Farah Wani
Keyword(s):  
Current Knowledge ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Receptor Expression ◽  
Pathophysiological Mechanism ◽  
Gi Tract ◽  
Wholesale Market ◽  
Main Mode ◽  
First Case ◽  
Organ Systems

Believed to have originated from a local Huanan Seafood Wholesale Market in Wuhan, Hubei Province in China, the COVID-19 has had an unprecedented and catastrophic impact on humanity, with the WHO declaring it a global pandemic. Although the first case of COVID-19 was reported in December 2019, the primary source and intermediate host have not been confirmed, but human-to-human transmission has been universally accepted. The main mode of transmission of the virus is through respiratory droplets along with prominent respiratory system involvement. However, fecal-oral transmission due to the shedding of the virus in the gastrointestinal (GI) tract may continue for up to 10 weeks after respiratory clearance and is fast becoming important. SARS-CoV-2 shows a high affinity to ACE2 receptors, making sites of high ACE2 receptor expression, such as lungs, GI tract, brain, kidneys, heart, liver and immune system, a prime target for infection. Through this literature review, we aim to summarize the current knowledge of immunological pathways that contribute to the disease with a focus specifically on the GI tract involvement. We direct attention to the pathophysiological mechanism of involvement of the GI tract leading to symptomatic manifestations, track GI organ-specific viral loads to compare and contrast with other organ systems. We briefly detail specific treatment strategies from a GI disease standpoint and mention special considerations when there is involvement of the GI tract.

scholarly journals C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Nóra Garam ◽  
Zoltán Prohászka ◽  
Ágnes Szilágyi ◽  
Christof Aigner ◽  
Alice Schmidt ◽  
...  
Keyword(s):  
Immune Complex ◽  
Membranoproliferative Glomerulonephritis ◽  
Alternative Pathway ◽  
Classical Pathway ◽  
Complement Alternative Pathway ◽  
Nephritic Factor ◽  
C3 Nephritic Factor ◽  
Hemolytic Assay ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors. Results One hunfe IC-MPGN/C3G patients were enrolled in the study. C4NeF activity was determined by hemolytic assay utilizing sensitized sheep erythrocytes. Seventeen patients were positive for C4NeF with lower prevalence of renal impairment and lower C4d level, and higher C3 nephritic factor (C3NeF) prevalence at time of diagnosis compared to C4NeF negative patients. Patients positive for both C3NeF and C4NeF had the lowest C3 levels and highest terminal pathway activation. End-stage renal disease did not develop in any of the C4NeF positive patients during follow-up period. Positivity to other complement autoantibodies (anti-C1q, anti-C3) was also linked to the presence of nephritic factors. Unsupervised, data-driven cluster analysis identified a group of patients with high prevalence of multiple complement autoantibodies, including C4NeF. Conclusions In conclusion, C4NeF may be a possible cause of complement dysregulation in approximately 10–15% of IC-MPGN/C3G patients.

scholarly journals Reassessment of renal prognosis in patients with membranoproliferative glomerulonephritis according to the new pathologic classification

2020 ◽  
pp. 23-28
Author(s):  
Ergün Parmaksız ◽  
Meral Meşe
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Membranoproliferative Glomerulonephritis ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Response To Treatment ◽  
Pathologic Classification ◽  
Stage Renal Disease ◽  
End Stage

Membranoproliferative glomerulonephritis (MPGN) is a heterogeneous disease characterized by a morphological injury pattern that can be seen under various disease conditions that share common pathogenic mechanisms. In this study, we analyzed clinical features, pathological findings, long-term kidney outcomes according to the new pathohistological classification of MPGN. Methods. This retrospective study included 20 CKD patients with biopsy-proven MPGN that had been diagnosed between 2011 and 2019. We reclassified the patterns of MPGN as immune-complexes mediated (ICM) and complement-mediated (CM) according to the new classification. Results. The level of daily proteinuria was lower in the ICM MPGN than the CM MPGN group but was not statistically significant at the end of the study. Histopathologically, the difference in C3 staining was found between the patients with ICM and CM MPGN. At the end of the follow-up period, no patients developed end-stage renal disease, and no death occurred in response to treatment in the ICM MPGN group. In the CM MPGN group, 2 patients evolved to end-stage renal disease and 1 of them had renal transplantation. Conclusion. Larger sample size and longer follow-up may change the relationship between histological factors, treatment strategies, and kidney outcomes. We believe that the use of the new diagnostic approach that applies to the ICM MPGN and CM MPGN will help nephrologists to improve treatment options and renal outcomes for patients with MPGN.

scholarly journals Immune Sensing and Potential Immunotherapeutic Approaches to Control Chromoblastomycosis

2020 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Leandro C. D. Breda ◽  
Isabela G. Menezes ◽  
Larissa N. M. Paulo ◽  
Sandro Rogério de Almeida
Keyword(s):  
Social Stigma ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Treatment Interruption ◽  
Lower Limbs ◽  
Disease Treatment ◽  
Immune Sensing ◽  
Skin Immunology ◽  
Anti Fungal ◽  
Made In

Chromoblastomycosis (CBM) is a neglected, chronic, and progressive subcutaneous mycosis caused by different species of fungi from the Herpotrichiellaceae family. CBM disease is usually associated with agricultural activities, and its infection is characterized by verrucous, erythematous papules, and atrophic lesions on the upper and lower limbs, leading to social stigma and impacts on patients’ welfare. The economic aspect of disease treatment is another relevant issue. There is no specific treatment for CBM, and different anti-fungal drug associations are used to treat the patients. However, the long period of the disease and the high cost of the treatment lead to treatment interruption and, consequently, relapse of the disease. In previous years, great progress had been made in the comprehension of the CBM pathophysiology. In this review, we discuss the differences in the cell wall composition of conidia, hyphae, and muriform cells, with a particular focus on the activation of the host immune response. We also highlight the importance of studies about the host skin immunology in CBM. Finally, we explore different immunotherapeutic studies, highlighting the importance of these approaches for future treatment strategies for CBM.

scholarly journals Molecular Subtypes and Precision Oncology in Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 10 (13) ◽  
pp. 2803
Author(s):  
Carolin Czauderna ◽  
Martha M. Kirstein ◽  
Hauke C. Tews ◽  
Arndt Vogel ◽  
Jens U. Marquardt
Keyword(s):  
Clinical Care ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Growth Factor Receptor ◽  
Treatment Modalities ◽  
Precision Oncology ◽  
Recurrence Rates ◽  
Isocitrate Dehydrogenase 1 ◽  
Liver Cancers

Cholangiocarcinomas (CCAs) are the second-most common primary liver cancers. CCAs represent a group of highly heterogeneous tumors classified based on anatomical localization into intra- (iCCA) and extrahepatic CCA (eCCA). In contrast to eCCA, the incidence of iCCA is increasing worldwide. Curative treatment strategies for all CCAs involve oncological resection followed by adjuvant chemotherapy in early stages, whereas chemotherapy is administered at advanced stages of disease. Due to late diagnosis, high recurrence rates, and limited treatment options, the prognosis of patients remains poor. Comprehensive molecular characterization has further revealed considerable heterogeneity and distinct prognostic and therapeutic traits for iCCA and eCCA, indicating that specific treatment modalities are required for different subclasses. Several druggable alterations and oncogenic drivers such as fibroblast growth factor receptor 2 gene fusions and hotspot mutations in isocitrate dehydrogenase 1 and 2 mutations have been identified. Specific inhibitors have demonstrated striking antitumor activity in affected subgroups of patients in phase II and III clinical trials. Thus, improved understanding of the molecular complexity has paved the way for precision oncological approaches. Here, we outline current advances in targeted treatments and immunotherapeutic approaches. In addition, we delineate future perspectives for different molecular subclasses that will improve the clinical care of iCCA patients.

scholarly journals The Therapeutic Effect of Extracellular Vesicles on Asthma in Pre-Clinical Models: A Systematic Review Protocol

2021 ◽  
Vol 1 (1) ◽  
pp. 84-95
Author(s):  
Patience O. Obi ◽  
Jennifer E. Kent ◽  
Maya M. Jeyaraman ◽  
Nicole Askin ◽  
Taiana M. Pierdoná ◽  
...  
Keyword(s):  
Systematic Review ◽  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Grey Literature ◽  
Specific Treatment ◽  
Therapeutic Effects ◽  
Management Options ◽  
Paracrine Signalling

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.

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