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C3 nephropathy

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https://www.readbyqxmd.com/read/28843828/vinpocetine-mitigates-proteinuria-and-podocytes-injury-in-a-rat-model-of-diabetic-nephropathy
#1
Walaa Wadie, Dalia M El-Tanbouly
Podocyte injury and glomerular basement membrane thickening have been considered as essential pathophysiological events in diabetic nephropathy. The aim of this study was to investigate the possible beneficial effects of vinpocetine on diabetes-associated renal damage. Male Wistar rats were made diabetic by injection of streptozotocin (STZ). Diabetic rats were treated with vinpocetine in a dose of 20mg/kg/day for 6 weeks. Treatment with vinpocetine resulted in a marked decrease in the levels of blood glucose, glycosylated haemoglobin, creatinine, blood urea nitrogen, urinary albumin and albumin/creatinine ratio along with an elevation in creatinine clearance rate...
August 24, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28838443/first-treatment-of-relapsing-rapidly-progressive-iga-nephropathy-with-eculizumab-after-living-kidney-donation-a-case-report
#2
A L Herzog, C Wanner, K Amann, K Lopau
BACKGROUND: IgA nephropathy (IGAN) rarely can present as a crescent and progressive form leading to end-stage renal disease (ESRD) in a short period of time. Recurrence of IGAN after kidney transplantation is frequent, and complement components such as C3, C4d, and C5 seem to be involved. We present a case of a young male patient with ESRD caused by rapidly progressive IGAN and who demonstrated rapid recurrence of crescentic IGAN after kidney donation. CASE REPORT: In September 2014, a 28-year-old male patient was hospitalized due to IGAN with 60% of crescents...
September 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28832357/recurrent-glomerular-disease-after-kidney-transplantation
#3
Christopher D Blosser, Roy D Bloom
PURPOSE OF REVIEW: With improving short-term kidney transplant outcomes, recurrent glomerular disease is being increasingly recognized as an important cause of chronic allograft failure. Further understanding of the risks and pathogenesis of recurrent glomerular disease enable informed transplant decisions, along with the development of preventive and treatment strategies. RECENT FINDINGS: Multiple observational studies have highlighted differences in rates and outcomes for various recurrent glomerular diseases, although these rates have not markedly improved over the last decade...
August 21, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28830653/recombinant-human-igg1-based-fc-multimers-with-limited-fcr-binding-capacity-can-effectively-inhibit-complement-mediated-disease
#4
Haoping Sun, Henrik S Olsen, Emmanuel Y Mérigeon, Edward So, Erin Burch, Susan Kinsey, John C Papadimitriou, Cinthia B Drachenberg, Søren M Bentzen, David S Block, Scott E Strome, Xiaoyu Zhang
There is a lack of effective targeted therapies for the treatment of complement dependent diseases. We developed two recombinant Fc multimers, G207 and G211, with limited ability to interact with low/moderate affinity FcγRs, but with high avidity for C1q. These drugs effectively inhibited complement dependent cytotoxicity (CDC) in vitro, and prevented the deposition of C1q, C3b and MAC, on the surface of Ab-opsonized cells. Importantly, these inhibitory effects were both C1q dependent and independent. In order to determine the biologic relevance of our findings, we evaluated the clinical efficacy of these drugs in three different animal models, acute RBC hemolysis, anti-Thy-1 nephritis and passive Heymann's nephropathy (PHN), in which disease pathophysiology relies preferentially on complement activation...
August 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28821363/living-donor-kidney-transplantation-in-atypical-hemolytic-uremic-syndrome-a-case-series
#5
Caroline Duineveld, Jacobien C Verhave, Stefan P Berger, Nicole C A J van de Kar, Jack F M Wetzels
BACKGROUND: The development of complement inhibitors has greatly improved the outcome of patients with atypical hemolytic uremic syndrome (aHUS), making kidney transplantation a more feasible option. Although prophylactic eculizumab therapy may prevent recurrent disease after transplantation, its necessity for all transplant recipients is debated. STUDY DESIGN: A case series. SETTING & PARTICIPANTS: Patients with aHUS who underwent living donor kidney transplantation after 2011 at 2 university centers, prospectively followed up with a protocol of eculizumab therapy limited to only recipients with documented posttransplantation recurrent thrombotic microangiopathy...
August 16, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28793954/interstitial-complement-c3-activation-and-macrophage-infiltration-in-patients-with-hypertensive-nephropathy%C3%A2
#6
Jiong Cui, Jianxin Wan, Danyu You, Zhenhuan Zou, Yi Chen, Zhenzhou Li, Qiujian Lian
BACKGROUND: The interplay between interstitial complement C3 activation and macrophage infiltration might play an important role in the pathogenesis of hypertensive nephropathy (HN), but human data are limited. We sought to investigate interstitial complement C3 expression and macrophage infiltration in HN as well as the relationships between C3 activation and macrophage infiltration, their association with clinicopathologic data, and changes in renal function. MATERIALS AND METHODS: Using immunohistochemistry, we analyzed 20 renal tissue specimens from HN patients and 40 control specimens for complement C3, angiotensin (AGT), angiotensin II, and macrophage marker CD68 levels...
August 10, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28729648/a-haplotype-in-cfh-family-genes-confers-high-risk-of-rare-glomerular-nephropathies
#7
Yin Ding, Weiwei Zhao, Tao Zhang, Hao Qiang, Jianping Lu, Xin Su, Shuzhen Wen, Feng Xu, Mingchao Zhang, Haitao Zhang, Caihong Zeng, Zhihong Liu, Huimei Chen
Despite distinct renal lesions, a series of rare glomerular nephropathies are reportedly mediated by complement overactivation. Genetic variations in complement genes contribute to disease risk, but the relationship of genotype to phenotype has not been straightforward. Here, we screened 11 complement genes from 91 patients with atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G) and membranoproliferative glomerulonephritis type I (MPGN I), and identified the concomitant presence of three missense variations located within the human complement Factor H (CFH) gene cluster...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697742/increased-c4-and-decreased-c3-levels-are-associated-with-a-poor-prognosis-in-patients-with-immunoglobulin-a-nephropathy-a-retrospective-study
#8
Min Pan, Ji Zhang, Zhanyuan Li, Lingwei Jin, Yu Zheng, Zhihong Zhou, Su Zhen, Guoyuan Lu
BACKGROUND: An association between serum complement levels and poor renal prognosis in patients with immunoglobulin A nephropathy (IgAN) remains controversial. METHODS: We conducted a retrospective study examining the relationship between serum complement levels and prognosis in patients with IgAN. Between 2009 and 2013, patients with biopsy-confirmed IgAN were identified from the Second Affiliated Hospital of Wenzhou Medical College, China, and various parameters were documented during follow-up until 2015...
July 11, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28658762/role-of-immunofluorescence-in-adult-onset-nephrotic-syndrome-a-study-in-a-tertiary-care-centre-of-western-india
#9
Sharada Rane, Prerana Mutyal, Nicholas Dcunha, Mayur Parkhi, Meenal Jadhav
INTRODUCTION: Study of renal Immunofluorescence (IF) is an ancillary but essential technique in evaluation of renal biopsies in glomerulopathies and also it enlightens on the pathogenesis of nephrotic syndrome. AIM: To determine the role of IF in evaluating definite subtyping and diagnosis of adult onset nephrotic syndrome and attempting clinicopathological correlation. MATERIALS AND METHODS: A total of 52 patients of adult onset nephrotic syndrome were evaluated clinically and with pertinent investigations; and subjected to USG guided percutaneous renal biopsy which was processed and stained for light microscopy and for immunofluorescence by direct method (DIF) using antibodies against IgG, IgM, IgA and C3...
May 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28637589/elevated-factor-h-related-protein-1-and-factor-h-pathogenic-variants-decrease-complement-regulation-in%C3%A2-iga-nephropathy
#10
Agustín Tortajada, Eduardo Gutiérrez, Elena Goicoechea de Jorge, Jaouad Anter, Alfons Segarra, Mario Espinosa, Miquel Blasco, Elena Roman, Helena Marco, Luis F Quintana, Josué Gutiérrez, Sheila Pinto, Margarita Lopez-Trascasa, Manuel Praga, Santiago Rodriguez de Córdoba
IgA nephropathy (IgAN), a frequent cause of chronic kidney disease worldwide, is characterized by mesangial deposition of galactose-deficient IgA1-containing immune complexes. Complement involvement in IgAN pathogenesis is suggested by the glomerular deposition of complement components and the strong protection from IgAN development conferred by the deletion of the CFHR3 and CFHR1 genes (ΔCFHR3-CFHR1). Here we searched for correlations between clinical progression and levels of factor H (FH) and FH-related protein 1 (FHR-1) using well-characterized patient cohorts consisting of 112 patients with IgAN, 46 with non-complement-related autosomal dominant polycystic kidney disease (ADPKD), and 76 control individuals...
June 18, 2017: Kidney International
https://www.readbyqxmd.com/read/28632965/frequent-col4-mutations-in-familial-microhematuria-accompanied-by-later-onset-alport-nephropathy-due-to-focal-segmental-glomerulosclerosis
#11
Louiza Papazachariou, Gregory Papagregoriou, Despina Hadjipanagi, Panagiota Demosthenous, Konstantinos Voskarides, Constantina Koutsofti, Kostas Stylianou, Petros Ioannou, Dimitris Xydakis, Ioannis Tzanakis, Antonia Papadaki, Nicolaos Kallivretakis, Nicolaos Nikolakakis, Garyfalia Perysinaki, Daniel P Gale, Athanasios Diamantopoulos, Pavlos Goudas, Dimitris Goumenos, Andreas Soloukides, Ioannis Boletis, Christina Melexopoulou, Eleni Georgaki, Elena Frysira, Fifi Komianou, Dimitrios Grekas, Christos Paliouras, Polichronis Alivanis, George Vergoulas, Alkis Pierides, Eugenios Daphnis, Constantinos Deltas
Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using Next Generation Sequencing (NGS) for five genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, nine of them novel...
June 20, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28573137/rituximab-for-treatment-of-membranoproliferative-glomerulonephritis-and-c3-glomerulopathies
#12
REVIEW
Michael Rudnicki
Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28535523/mycophenolate-mofetil-a-possible-alternative-treatment-for-iga-nephropathy
#13
Olga Baraldi, Giorgia Comai, Vania Cuna, Maria Cappuccilli, Carla Serra, Claudio Ronco, Gaetano La Manna
IgA nephropathy (IgAN) is the most common primary glomerulonephritis in developed countries and a leading cause of chronic kidney disease. IgAN is a mesangial proliferative glomerulonephritis characterized by diffuse mesangial deposition of IgA, often accompanied by the deposition of IgG and the C3 component of complement in a similar distribution. This condition is in most cases oligosymptomatic, often discovered coincidentally. Currently, there is no specific treatment available for IgAN and the use of immunosuppression therapy is debated...
2017: Contributions to Nephrology
https://www.readbyqxmd.com/read/28487945/nox4-is-involved-in-high-glucose-induced-apoptosis-in-renal-tubular-epithelial-cells-via-notch-pathway
#14
Min Yao, Feng Gao, Xiaomeng Wang, Yonghong Shi, Shuxia Liu, Huijun Duan
It has previously been demonstrated that nicotinamide adenine dinucleotide phosphate‑oxidase (NADPH) oxidase 4 (Nox4), is important in the pathogenesis of diabetic nephropathy (DN), however the exact mechanisms remain to be elucidated. The present study aimed to examine the effect of Nox4 on the alteration of the Notch pathway and cell apoptosis in the renal tubular epithelial cell line, HKC, under conditions of high glucose (HG; 30 mmol/l glucose). Nox4 and the Notch pathway were inhibited by N‑acetylcysteine (NAC), diphenylene iodonium (DPI) or γ‑secretase inhibitor (DAPT)...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28396151/increased-urine-acylcarnitines-in-diabetic-apoe-mice-hydroxytetradecadienoylcarnitine-c14-2-oh-reflects-diabetic-nephropathy-in-a-context-of-hyperlipidemia
#15
Koryun Mirzoyan, Kristaps Klavins, Therese Koal, Marion Gillet, Dimitri Marsal, Colette Denis, Julie Klein, Jean-Loup Bascands, Joost P Schanstra, Jean-Sébastien Saulnier-Blache
Hyperlipidemia is a risk factor for initiation and progression of diabetic nephropathy but the metabolic pathways altered in the diabetic kidney in a context of hyperlipidemia remain incompletely described. Assuming that changes in urine composition reflect the alteration of renal metabolism and function, we analyzed the urine metabolite composition of diabetic (streptozotocin-treatment) and control (non diabetic) ApoE-/- mice fed a high cholesterol diet using targeted quantitative metabolomics. Urine metabolome was also compared to the plasma metabolome of the same animals...
May 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28355401/schistosoma-mansoni-associated-glomerulopathy-with-iga-mesangial-deposits-case-report
#16
Fabiana Oliveira Gonçalves, Tânia Maria de Souza Fontes, Ana Paula Pereira Santana Lemes Canuto
INTRODUCTION: Renal involvement is a severe form of schistosomiasis and occurs in 10% to 15% of patients with the hepatosplenic form of the disease. Nephrotic syndrome is the most common clinical presentation. It is a complication caused by immune complexes (IC), it is rare to appear in the Brazilian context with a immunoglobulin A (IgA) deposits. When installed the renal injury by Schistosoma mansoni, classically presents as membranoproliferative glomerulonephritis (mesangiocapillary) with lobular accentuation...
March 2017: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/28334051/dissecting-the-relationships-of-igg-subclasses-and-complements-in-membranous-lupus-nephritis-and-idiopathic-membranous-nephropathy
#17
Woong Na, Kijong Yi, Young Soo Song, Moon Hyang Park
Membranous lupus nephritis (MLN) and idiopathic membranous nephropathy (IMN) are kidney diseases with similar morphology, but distinct etiologies, both producing glomeruli with immune deposits. Immunoglobulins and complements, the main components of the deposits, can be detected by immunofluorescence (IF) microscopy. Previous researches characterized the immune deposits only individually, but not the interactions between them. To study these relationships we analyzed an IF profile of IgG subclasses and complements (IgG1, IgG2, IgG3, IgG4, C3, C1q, and C4) in 53 and 95 cases of biopsy-confirmed MLNs and IMNs, respectively, mainly using information theory and Bayesian networks...
2017: PloS One
https://www.readbyqxmd.com/read/28295247/targeting-c3a-c5a-receptors-inhibits-human-mesangial-cell-proliferation-and-alleviates-immunoglobulin-a-nephropathy-in-mice
#18
Y Zhang, X Yan, T Zhao, Q Xu, Q Peng, R Hu, S Quan, Y Zhou, G Xing
Complement activation has a deep pathogenic influence in immunoglobulin (Ig)A nephropathy (IgAN). C3a and C5a, small cleavage fragments generated by complement activation, are key mediators of inflammation. The fragments exert broad proinflammatory effects by binding to specific receptors (C3aR and C5aR, respectively). However, no studies thus far have investigated the effects of C3a, C5a and their receptors on IgAN. We observed that C3aR and C5aR antagonists repressed IgA-induced cell proliferation and interleukin (IL)-6 and monocyte chemotactic protein 1 (MCP-1) production in cultured human mesangial cells (HMCs)...
July 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28291506/immunotactoid-glomerulopathy-leading-to-the-discovery-of-poems-syndrome%C3%A2
#19
Carole Philipponnet, Jean-Louis Kemeny, Cyril Garrouste, Martin Soubrier, Anne-Elisabeth Heng
Monoclonal gammopathy of renal significance (MGRS) can manifest in many different ways depending on the nature of the immunoglobulin and its physicochemical properties. MGRS can lead to the discovery of a hematological malignancy. We report the case of a 32-year-old female patient who underwent renal biopsy on account of an impure nephrotic syndrome associated with immunoglobulin (Ig)G κ monoclonal gammopathy. Histological analysis revealed membranoproliferative glomerulonephritis with IgG, IgM, κ, λ, and C3 deposits...
March 14, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28262777/the-role-of-the-complement-system-in-diabetic-nephropathy
#20
REVIEW
Allan Flyvbjerg
The development of type 1 and type 2 diabetes mellitus has a substantial negative impact on morbidity and mortality and is responsible for substantial individual and socioeconomic costs worldwide. One of the most serious consequences of diabetes mellitus is the development of diabetic angiopathy, which manifests clinically as microvascular and macrovascular complications. One microvascular complication, diabetic nephropathy, is the most common cause of end-stage renal disease in developed countries. Although several available therapeutic interventions can delay the onset and progression of diabetic nephropathy, morbidity associated with this disease remains high and new therapeutic approaches are needed...
May 2017: Nature Reviews. Nephrology
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