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C3 nephropathy

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28203107/clinical-validation-of-immunoglobulin-a-nephropathy-diagnosis-in-swedish-biopsy-registers
#12
Simon Jarrick, Sigrid Lundberg, Adina Welander, C Michael Fored, Jonas F Ludvigsson
AIMS: The aims of this study were to validate the diagnosis of IgA nephropathy (IgAN) in Swedish biopsy registers against patient charts and to describe the clinical characteristics of patients with a biopsy indicating IgAN. METHODS: This is a population-based cohort study. Out of 4,069 individuals with a renal biopsy consistent with IgAN (biopsies performed in 1974-2011), this study reviewed patient charts of a random subset of 127 individuals. Clinical and biopsy characteristics at the time of biopsy were evaluated, and positive predictive values (PPV) were calculated with 95% confidence intervals (CI)...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28182703/nephropathy-in-pparg-null-mice-highlights-ppar%C3%AE-systemic-activities-in-metabolism-and-in-the-immune-system
#13
Barbara Toffoli, Federica Gilardi, Carine Winkler, Magnus Soderberg, Laura Kowalczuk, Yvan Arsenijevic, Krister Bamberg, Olivier Bonny, Béatrice Desvergne
Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-dependent transcription factor involved in many aspects of metabolism, immune response, and development. Total-body deletion of the two Pparg alleles provoked generalized lipoatrophy along with severe type 2 diabetes. Herein, we explore the appearance and development of structural and functional alterations of the kidney, comparing Pparg null-mice to their littermate controls (carrying Pparg floxed alleles). We show that renal hypertrophy and functional alterations with increased glucosuria and albuminuria are already present in 3 weeks-old Pparg null-mice...
2017: PloS One
https://www.readbyqxmd.com/read/28166191/decreased-serum-c3-levels-in-immunoglobulin-a-iga-nephropathy-with-chronic-kidney-disease-a-propensity-score-matching-study
#14
Xi Yang, Ri-Bao Wei, Yang Wang, Ting-Yu Su, Qing-Ping Li, Ting Yang, Meng-Jie Huang, Kun-Ying Li, Xiang-Mei Chen
BACKGROUND The effects of low serum C3 levels and the activation of the complement system on the development and the prognosis of IgAN are unclear. The present study aimed to determine whether decreased levels of complement C3 influence the prognosis of IgAN patients with chronic kidney disease. MATERIAL AND METHODS We enrolled a total of 1564 patients with primary IgAN diagnosed by renal biopsy at the Chinese PLA General Hospital from January 2011 to March 2015. The endpoint was end-stage renal disease (ESRD) or a doubling of the baseline serum creatinine (D-SCr) level...
February 6, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28157068/clinical-and-pathological-characteristics-of-fabry-disease-combined-with-iga-nephropathy-in-chinese-patients%C3%A2
#15
Nannan Yang, Xia Wang, Feng Xu, Caihong Zeng, Jinquan Wang, Zhihong Liu
AIMS: To improve diagnosis and treatment, we characterized Fabry disease combined with IgA nephropathy and its response to treatment clinically and pathologically in Chinese patients. MATERIALS AND METHODS: Clinical and pathological characteristics of 6 Chinese patients with renal biopsy-proven Fabry disease combined with IgA nephropathy were retrospectively analyzed. RESULTS: There were 4 males and 2 females in this study. All of the 6 patients presented with proteinuria...
April 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28098102/evaluation-of-renal-lesions-and-clinicopathologic-correlation-in-rheumatoid-arthritis
#16
Periyasamy Muthukumar, Jeyachandran Dhanapriya, Natarajan Gopalakrishnan, Thanigachalam Dineshkumar, Ramanathan Sakthirajan, T Balasubramaniyan
The most common causes of renal disease in rheumatoid arthritis (RA) are glomerulonephritis (GN), amyloidosis, tubulo-interstitial nephritis, and drug toxicity. Our aim was to evaluate the clinicopathologic correlation of renal lesions and to assess the course and prognosis of renal disease in patients with RA. We conducted a prospective observational study in all adult patients with RA between July 2010 and June 2015. The total number of patients studied was 90, with a female:male ratio of 2.3:1. Mean follow-up duration was 30 ± 6...
January 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/27997722/pitavastatin-suppresses-hyperglycemia-induced-podocyte-injury-via-bone-morphogenetic-protein-7-preservation
#17
Makoto Ohigashi, Miyuki Kobara, Tamotsu Takahashi, Hiroe Toba, Takehiko Wada, Tetsuo Nakata
BACKGROUND: Podocytes form the essential components of the glomerular filtration barrier and play a critical role in diabetic nephropathy. Recent evidence suggests that HMG-CoA reductase inhibitors (statins) exert renoprotective effects. We investigated whether pitavastatin directly suppresses hyperglycemia-induced podocyte injury using cultured podocytes and, if so, the mechanism of the beneficial effects. METHODS AND RESULTS: Cultured podocytes were exposed to media containing normal (NG; 5 mmol/L) or high (HG; 25 mmol/L) glucose for one week...
December 20, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27977428/breaking-down-the-complement-system-a-review-and-update-on-novel-therapies
#18
Yuvaram N V Reddy, Andrew M Siedlecki, Jean M Francis
PURPOSE OF REVIEW: The complement system represents one of the more primitive forms of innate immunity. It has increasingly been found to contribute to pathologies in the native and transplanted kidney. We provide a concise review of the physiology of the complement cascade, and discuss current and upcoming complement-based therapies. RECENT FINDINGS: Current agents in clinical use either bind to complement components directly or prevent complement from binding to antibodies affixed to the endothelial surface...
March 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27942230/iga1-dominant-subclass-of-latent-iga-mesangial-deposition-in-donated-kidney
#19
Kazumasa Oka, Kenji Nishimura, Hidefumi Kishikawa, Yasuji Ichikawa
BACKGROUND: In the pathogenesis of immunoglobulin A nephropathy (IgAN), the IgA1 subclass is more important than the IgA2 subclass. In healthy men, the prevalence of mesangial IgA deposition has been previously investigated. However, it remains unknown whether the presence of urinary abnormalities depends on the subclass of IgA deposition. MATERIALS AND METHODS: We researched the subclasses of IgA (IgA1 and IgA2) by the direct immunofluorescence (IF) staining method using specimens in which we identified the deposition of IgA through zero-hour renal transplant biopsies from donors without urinary abnormalities...
2016: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/27821389/staphylococcus-infection-associated-gn-spectrum-of-iga-staining-and-prevalence-of-anca-in-a-single-center-cohort
#20
Anjali A Satoskar, Sarah Suleiman, Isabelle Ayoub, Jessica Hemminger, Samir Parikh, Sergey V Brodsky, Cherri Bott, Edward Calomeni, Gyongyi M Nadasdy, Brad Rovin, Lee Hebert, Tibor Nadasdy
BACKGROUND AND OBJECTIVES: Staphylococcus infection-associated GN (SAGN) is a well recognized disease entity, particularly because of the frequent IgA-dominant glomerular immunoglobulin staining on kidney biopsy. Biopsy features can resemble two other disease entities - primary IgA nephropathy and Henoch-Schönlein purpura nephritis - posing a diagnostic pitfall. This is clinically relevant because of the crucial difference in the therapeutic approach. The diagnosis of SAGN is further complicated by the variability in the degree of glomerular IgA (and C3) staining, the extent of electron dense immune-type deposits, and positive ANCA serology in some patients...
January 6, 2017: Clinical Journal of the American Society of Nephrology: CJASN
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