scholarly journals P0496THE IMPORTANCE OF COMPLEMENT LEVELS AND CLINICAL CHARACTERISTICS OF PRIMARY MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS IN TURKEY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Erhan Tatar ◽  
Deren Oygar ◽  
Nurhan Seyahi ◽  
Necmi Eren ◽  
Yağmur Cantürk ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Immune Complex ◽  
Membranoproliferative Glomerulonephritis ◽  
C3 Glomerulopathy ◽  
Complex Type ◽  
Glomerular Diseases ◽  
Nephritic Syndrome ◽  
Pathological Evaluation ◽  
Chronicity Index ◽  
The Complement System

Abstract Background and Aims Membranoproliferative glomerulonephritis (MPGN) may be caused by disturbances in the complement system. Hypocomplementemia is a characteristic of MPGN. Among these patients frequency of hypocomplementemia and their relation with clinical and histopathological findings are still not clearly known. The aim of this study is to evaluate the hypocomplementemia frequency among the primary MPGN patients in Turkey and its relation with histopathological subtypes, findings and demographic characteristics. Method The data was obtained from national multicentered (47 centers) records of primary glomerular diseases in Glomerulonephritis Study Group of the Turkish Society of Nephrology database from May 2009 to June 2019. Primary MPGN cases were evaluated and divided into 2 groups with and without hypocomplementemia. Results In total, 193 cases were included in the study. The indications for renal biopsy were isolated nephrotic syndrome (55.4%), nephritic syndrome (21.2%), nephrotic syndrome with a nephritic component (6.2%) and asymptomatic urinary findings (17.2%). 34.2% of the cases were reported as immune complex type, another 34.2% of the cases were reported as C3 glomerulopathy. 31.6% of patients were not specified. 82 (42.4%) of the cases presented hypocomplementemia. Hypocomplementemic patients were younger (34±14 vs 41±15, p=0.002) and most frequently female (56% vs 41%, p=0.03). At same time, serum albumin and hemoglobin levels were lower and anemic patient rates were higher (p<0.001). In this group, the nephrotic syndrome rates were higher (72% vs 54%, p=0,01). Hypocomplementemia rate in the C3 glomerulopathy was 52% (in DDD 40%, in C3GN 55% ) whereas in immune complex type 41% and in non specified type 34%. In the pathological evaluation; among the hypocomplementemic group the endocapillary proliferation and glomerular exudative differentiation rates presented significant increase. However the chronicity index were lower in the kidney biopsy (Table 1). Conclusion This multicenter study provided important data about the epidemiology of MPGN with importance of hypocomplementemia in Turkey. Hypocomplementemia is associated with both subtypes of MPGN patern, anemia and nephrotic syndrome. At the same time, hypocomplementemia is a valuable parameter for active MPGN pattern in the histopathological evaluation. This may be important in determining the treatment.

scholarly journals Different Aspects of Classical Pathway Overactivation in Patients With C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Marloes A. H. M. Michels ◽  
Nicole C. A. J. van de Kar ◽  
Sanne A. W. van Kraaij ◽  
Sebastian A. Sarlea ◽  
Valentina Gracchi ◽  
...  
Keyword(s):  
Immune Complex ◽  
Membranoproliferative Glomerulonephritis ◽  
Alternative Pathway ◽  
Classical Pathway ◽  
Healthy Controls ◽  
C3 Glomerulopathy ◽  
Hemolytic Assay ◽  
The Stability ◽  
The Complement System

The rare and heterogeneous kidney disorder C3 glomerulopathy (C3G) is characterized by dysregulation of the alternative pathway (AP) of the complement system. C3G is often associated with autoantibodies stabilizing the AP C3 convertase named C3 nephritic factors (C3NeF). The role of classical pathway (CP) convertase stabilization in C3G and related diseases such as immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) remains largely unknown. Here, we investigated the CP convertase activity in patients with C3G and IC-MPGN. Using a refined two-step hemolytic assay, we measured the stability of CP convertases directly in the serum of 52 patients and 17 healthy controls. In four patients, CP convertase activity was prolonged compared to healthy controls, i.e. the enzymatic complex was stabilized. In three patients (2 C3G, 1 IC-MPGN) the convertase stabilization was caused by immunoglobulins, indicating the presence of autoantibodies named C4 nephritic factors (C4NeFs). Importantly, the assay also enabled detection of non-immunoglobulin-mediated stabilization of the CP convertase in one patient with C3G. Prolonged CP convertase activity coincided with C3NeF activity in all patients and for up to 70 months of observation. Crucially, experiments with C3-depleted serum showed that C4NeFs stabilized the CP C3 convertase (C4bC2a), that does not contain C3NeF epitopes. All patients with prolonged CP convertase activity showed clear signs of complement activation, i.e. lowered C3 and C5 levels and elevated levels of C3d, C3bc, C3bBbP, and C5b-9. In conclusion, this work provides new insights into the diverse aspects and (non-)immunoglobulin nature of factors causing CP convertase overactivity in C3G/IC-MPGN.

Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis

2020 ◽  
Author(s):  
Priyanka Khandelwal ◽  
Swati Bhardwaj ◽  
Geetika Singh ◽  
Aditi Sinha ◽  
Pankaj Hari ◽  
...  
Keyword(s):  
Immune Complex ◽  
Membranoproliferative Glomerulonephritis ◽  
C3 Glomerulopathy

scholarly journals CFHR5 Genetic Variations and Serum Levels in Patients with Immune-Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy

2020 ◽  
Author(s):  
Nóra Garam ◽  
Marcell Cserhalmi ◽  
Zoltán Prohászka ◽  
Ágnes Szilágyi ◽  
Nóra Veszeli ◽  
...  
Keyword(s):  
Immune Complex ◽  
Membranoproliferative Glomerulonephritis ◽  
Kidney Diseases ◽  
Alternative Pathway ◽  
Serum Levels ◽  
Genetic Alterations ◽  
Factor H ◽  
Complement Factor ◽  
C3 Glomerulopathy

Abstract Background: Factor H-related-5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement and follow-up data.Results: 120 patients with a histologically-proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger-sequencing, and selected mutants were studied as recombinant proteins in ELISA and SPR.Eight relevant CFHR5 variations in 14 patients (11.7%) were observed, 5 of them identified as pathogenic for C3G. The FHR-5G278S and FHR-5R356H mutations altered the interaction of FHR-5 with C3b, when compared to the FHR-5WT. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period, furthermore, it showed clear association with signs of hypocomplementemia and clinically meaningful clusters.Conclusions: Our observations support the hypothesis that FHR-5 protein and its genetic alterations play a role in the pathogenesis of IC-MPGN/C3G.

scholarly journals A Pattern of Glomerular Diseases in Egyptian Children: A Single-center Experience

2021 ◽  
Vol 9 (B) ◽  
pp. 1305-1312
Author(s):  
Hoda Atef Abdelsattar Ibrahim ◽  
Aya Amin ◽  
Ahmed Zeid ◽  
Samar Sabry ◽  
Hesham Safouh
Keyword(s):  
Nephrotic Syndrome ◽  
Iga Nephropathy ◽  
Glomerular Disease ◽  
Diffuse Mesangial Sclerosis ◽  
Gross Hematuria ◽  
Glomerular Diseases ◽  
Nephritic Syndrome ◽  
Study Results ◽  
Egyptian Children ◽  
Membranous Gn

BACKGROUND: Findings indicative of the glomerular disease are proteinuria, hematuria, nephrotic syndrome (NS), hypertension, and renal insufficiency. These presentations can be used to define different clinical patterns that resemble different underlying etiologies. METHODS: This study is a cross-sectional study enrolled in Children Hospital Cairo University. The study participants were recruited on two stages, retrospective and prospective stages. In the retrospective stage, all eligible patients across 5 years (between 2011 and 2015) with any glomerular disease were included in the study. In addition, prospectively, the new cases a long 6 months (from February 2016 till July 2016) with glomerular diseases were included in the study. RESULTS: A total of 594 cases with different glomerular diseases were identified. Cases were two groups: The retrospective group that involved 543 cases and the prospective group that included 51 cases. In the retrospective part of the study, the most common presentations were NS (68%), nephritis (16.4%), gross hematuria (10.5%), and nephrotic/nephritic syndrome (3.5%). The most common biopsies in the retrospective study were NS: MCNS (27.3%), NS: focal segmental glomerulosclerosis (FSGS) (23.4%), NS: Mesangioproliferative GN (9.4%), NS: Membranous GN (2.3%), Crescentric GN (3.9%), Membranous GN (0.8%), MPGN (0.8%), congenital nephrotic syndrome (CNS):Diffuse Mesangial Sclerosis (3.9%), CNS: Finnish type (2.3%), Alport (4.7%), IgA nephropathy (3.9%), IgM nephropathy (1.6%), lupus nephritis (LN) (3.1%), Thin basement membrane disease (3.1%), and others (9.4%) In the prospective study, the most common presentations were NS (76.5%), nephritis (11.8%), nephrotic/nephritic syndrome (7.8%), and gross hematuria (3.9%). The biopsies results were mainly NS: FSGS (33.3%) and NS: MCNS (33.3%). Other biopsies results in the prospective part were NS: Mesangioproliferative GN (16.7%), LN (8.3%), and IgA nephropathy (8.3%). CONCLUSION: The most common glomerular disease in childhood is NS. The most common pathology of glomerular diseases is minimal change NS.

scholarly journals Blood Oxygen Level-Dependent (BOLD) MRI in Glomerular Disease

2021 ◽  
Vol 2 (2) ◽  
pp. 109-117
Author(s):  
Daniel R. Nemirovsky ◽  
Puneet Gupta ◽  
Sophia Hu ◽  
Raymond Wong ◽  
Avnesh S. Thakor
Keyword(s):  
Nephrotic Syndrome ◽  
Blood Oxygen Level Dependent ◽  
Glomerular Disease ◽  
Blood Oxygen ◽  
Oxygen Level ◽  
Blood Oxygen Level ◽  
Glomerular Diseases ◽  
Bold Mri ◽  
Bold Imaging ◽  
Nephritic Syndrome

Renal hypoxia has recently been implicated as a key contributor and indicator of various glomerular diseases. As such, monitoring changes in renal oxygenation in these disorders may provide an early diagnostic advantage that could prevent potential adverse outcomes. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) is an emerging noninvasive technique for assessing renal oxygenation in glomerular disease. Although BOLD MRI has produced promising initial results for the use in certain renal pathologies, the use of BOLD imaging in glomerular diseases, including primary and secondary nephrotic and nephritic syndromes, is relatively unexplored. Early BOLD studies on primary nephrotic syndrome, nephrotic syndrome secondary to diabetes mellitus, and nephritic syndrome secondary to systemic lupus erythematosus have shown promising results to support its future clinical utility. In this review, we outline the advancements made in understanding the use of BOLD MRI for the assessment, diagnosis, and screening of these pathologies.

scholarly journals The Spectrum of Biopsy-Proven Glomerular Diseases in a Tertiary Hospital in Southern Brazil

2021 ◽  
Author(s):  
Gustavo Gomes Thomé ◽  
Talissa Bianchini ◽  
Rafael Nazario Bringhenti ◽  
Pedro Guilherme Schaefer ◽  
Elvino José Guardão Barros ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Temporal Variation ◽  
Kidney Biopsy ◽  
Systemic Vasculitis ◽  
Laboratory Data ◽  
Tertiary Hospital ◽  
Age Group ◽  
Glomerular Diseases ◽  
Nephritic Syndrome ◽  
Time Periods

Abstract Background The prevalence and distribution of glomerular diseases differs between countries, and the indication to perform a kidney biopsy varies in each center. In this study, we assessed the prevalence of primary and secondary glomerulopathies based on histological diagnosis, and their correlation with demographic and clinical data were evaluated. Methods It was included in the study 1051 kidney biopsies retrospectively reviewed between the years 2000 to 2018. Demographic, clinical and laboratory data of patients were assessed. The prevalence of primary glomerulonephritis (PG) and secondary glomerulopathies (SG), as well as tubulo-interstitial diseases (TID), hereditary nephropathies (HN) and other diagnosis, were described. The frequency of primary and secondary glomerulopathies was evaluated by age group, and their temporal variation in three time periods (2000–2005, 2006–2011, and 2012–2018) were reported. Results The prevalence of SG predominated (52.4%) followed by PG (29.6%), other diagnoses (10.7%), TID (6.6%) and HN (1.1%). In primary forms, focal segmental glomerulosclerosis (FSGS) prevailed (37.3%), followed by IgA nephropathy (IgAN, 24.4%), membranous nephropathy (MN, 18.6%) and minimal change disease (MCD, 8.4%). Lupus nephritis (LN, 41.1%) had the highest frequency in SG, and in sequence diabetic kidney disease (DKD, 17.8%), systemic vasculitis (SV, 10.2%) and secondary FSGS (2nd FSGS, 10%). Nephrotic syndrome was the most common clinical presentation in PG, and also in DRD and 2nd FSGS, whereas in IgAN and SV the nephritic syndrome was the main form of presentation. In the age group between 18–50 years, LN, FSGS and IgAN predominated, between 51–65 years the proportion of DKD and 2nd FSGS increased, and SV were more found in patients > 65 years. The temporal variation of PG in three time periods showed a statistically significant increase in IgAN (p = 0.001) and a reduction in FSGS (p < 0.001). In SG, there were a reduction in LN (p = 0.027) and increase in DKD (p < 0.001), with a tendency to decrease of 2nd FSGS (p = 0.053). Conclusions In this kidney biopsy registry, FSGS and IgAN were the prevalent diagnoses in PG, ​​and LN and DKD in SG. Nephrotic syndrome was the major indication for biopsy. When comparing the temporal variation of glomerulopathies, there was a reduction in FSGS and an increase in IgAN in PGs, and in SGs a reduction of LN with an increase in cases of DKD.

scholarly journals The spectrum of biopsy-proven glomerular diseases in a tertiary Hospital in Southern Brazil

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gustavo Gomes Thomé ◽  
Talissa Bianchini ◽  
Rafael Nazario Bringhenti ◽  
Pedro Guilherme Schaefer ◽  
Elvino José Guardão Barros ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Temporal Variation ◽  
Kidney Biopsy ◽  
Systemic Vasculitis ◽  
Laboratory Data ◽  
Age Group ◽  
Glomerular Diseases ◽  
Nephritic Syndrome ◽  
Time Periods ◽  
Over Time

Abstract Background The prevalence and distribution of glomerular diseases differ among countries, and the indication to perform a kidney biopsy varies among centres. In this study, we assessed the prevalence of primary and secondary glomerulopathies based on histological diagnoses, and the correlation between glomerulopathies and demographic and clinical data was evaluated. Methods In this study, 1051 kidney biopsies were retrospectively reviewed between 2000 and 2018. Patient demographic, clinical and laboratory data were assessed. The prevalence of primary glomerulonephritis (PG) and secondary glomerulopathies (SG), as well as tubulointerstitial diseases (TIDs), hereditary nephropathies (HNs) and other diagnoses, were determined. The frequency of primary and secondary glomerulopathies was evaluated by age group, and the temporal variation in frequencies across three time periods (2000-2005, 2006-2011, and 2012-2018) was reported. Results The prevalence of SG predominated (52.4%), followed by PG (29.6%), other diagnoses (10.7%), TID (6.6%) and HN (1.1%). Among the primary forms of glomerular disease, focal segmental glomerulosclerosis (FSGS) was the most common (37.3%), followed by IgA nephropathy (IgAN, 24.4%), membranous nephropathy (MN, 18.6%) and minimal change disease (MCD, 8.4%). Lupus nephritis (LN, 41.1%) was most common in patients with SG, followed by diabetic kidney disease (DKD, 17.8%), systemic vasculitis (SV, 10.2%) and secondary FSGS (2nd FSGS, 10%). Nephrotic syndrome was the most common clinical presentation in patients with PG and also in patients with DRD and 2nd FSGS, whereas in patients with IgAN and SV, nephritic syndrome was the main presentation. For the age group between 18 and 50 years, LN, FSGS and IgAN predominated; for patients aged between 51 and 65 years, the proportion of DKD and 2nd FSGS increased, and SV was more common in patients > 65 years. The temporal variation in PG across the three time periods showed a statistically significant increase in IgAN (p = 0.001) and a reduction in FSGS over time (p < 0.001). In SG, there was a reduction in LN (p = 0.027) and an increase in DKD (p < 0.001) over time, with a tendency for 2nd FSGS to decrease over time (p = 0.053). Conclusions In the studied kidney biopsy registry, FSGS and IgAN were the most prevalent diagnoses in patients with PG, and LN and DKD were the most prevalent in patients with SG. Nephrotic syndrome was the major indication for biopsy. When comparing the temporal variation in glomerulopathies, there was a reduction in FSGS and an increase in IgAN in patients with PGs over time, and for patients with SGs, there was a reduction in LN with an increase in cases of DKD over time.

scholarly journals FHR-5 Serum Levels and CFHR5 Genetic Variations in Patients With Immune Complex-Mediated Membranoproliferative Glomerulonephritis and C3-Glomerulopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Nóra Garam ◽  
Marcell Cserhalmi ◽  
Zoltán Prohászka ◽  
Ágnes Szilágyi ◽  
Nóra Veszeli ◽  
...  
Keyword(s):  
Immune Complex ◽  
Membranoproliferative Glomerulonephritis ◽  
Kidney Diseases ◽  
Alternative Pathway ◽  
Serum Levels ◽  
Factor H ◽  
Fine Tuning ◽  
Complement Factor ◽  
C3 Glomerulopathy

BackgroundFactor H-related protein 5 (FHR-5) is a member of the complement Factor H protein family. Due to the homology to Factor H, the main complement regulator of the alternative pathway, it may also be implicated in the pathomechanism of kidney diseases where Factor H and alternative pathway dysregulation play a role. Here, we report the first observational study on CFHR5 variations along with serum FHR-5 levels in immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) and C3 glomerulopathy (C3G) patients together with the clinical, genetic, complement, and follow-up data.MethodsA total of 120 patients with a histologically proven diagnosis of IC-MPGN/C3G were enrolled in the study. FHR-5 serum levels were measured in ELISA, the CFHR5 gene was analyzed by Sanger sequencing, and selected variants were studied as recombinant proteins in ELISA and surface plasmon resonance (SPR).ResultsEight exonic CFHR5 variations in 14 patients (12.6%) were observed. Serum FHR-5 levels were lower in patients compared to controls. Low serum FHR-5 concentration at presentation associated with better renal survival during the follow-up period; furthermore, it showed clear association with signs of complement overactivation and clinically meaningful clusters.ConclusionsOur observations raise the possibility that the FHR-5 protein plays a fine-tuning role in the pathogenesis of IC-MPGN/C3G.

scholarly journals CFH and CFHR Copy Number Variations in C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis

2021 ◽  
Vol 12 ◽  
Author(s):  
Rossella Piras ◽  
Matteo Breno ◽  
Elisabetta Valoti ◽  
Marta Alberti ◽  
Paraskevas Iatropoulos ◽  
...  
Keyword(s):  
Immune Complex ◽  
Single Molecule ◽  
Copy Number ◽  
Membranoproliferative Glomerulonephritis ◽  
Alternative Pathway ◽  
Copy Number Variations ◽  
Factor H ◽  
Complement C3 ◽  
Complement Factor ◽  
C3 Glomerulopathy

C3 Glomerulopathy (C3G) and Immune Complex-Mediated Membranoproliferative glomerulonephritis (IC-MPGN) are rare diseases characterized by glomerular deposition of C3 caused by dysregulation of the alternative pathway (AP) of complement. In approximately 20% of affected patients, dysregulation is driven by pathogenic variants in the two components of the AP C3 convertase, complement C3 (C3) and Factor B (CFB), or in complement Factor H (CFH) and Factor I (CFI), two genes that encode complement regulators. Copy number variations (CNVs) involving the CFH-related genes (CFHRs) that give rise to hybrid FHR proteins also have been described in a few C3G patients but not in IC-MPGN patients. In this study, we used multiplex ligation-dependent probe amplification (MLPA) to study the genomic architecture of the CFH-CFHR region and characterize CNVs in a large cohort of patients with C3G (n = 103) and IC-MPGN (n = 96) compared to healthy controls (n = 100). We identified new/rare CNVs resulting in structural variants (SVs) in 5 C3G and 2 IC-MPGN patients. Using long-read single molecule real-time sequencing (SMRT), we detected the breakpoints of three SVs. The identified SVs included: 1) a deletion of the entire CFH in one patient with IC-MPGN; 2) an increased number of CFHR4 copies in one IC-MPGN and three C3G patients; 3) a deletion from CFHR3-intron 3 to CFHR3-3′UTR (CFHR34–6Δ) that results in a FHR3-FHR1 hybrid protein in a C3G patient; and 4) a CFHR31–5-CFHR410 hybrid gene in a C3G patient. This work highlights the contribution of CFH-CFHR CNVs to the pathogenesis of both C3G and IC-MPGN.

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