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https://www.readbyqxmd.com/read/28550388/antibodies-against-linear-epitopes-on-goodpasture-autoantigen-in-patients-with-anti-neutrophil-cytoplasmic-antibody-associated-vasculitis
#1
Xiao-Yu Jia, Jun-Tao Yu, Shui-Yi Hu, Jian-Nan Li, Miao Wang, Chen Wang, Min Chen, Zhao Cui, Ming-Hui Zhao
In a substantial number of patients with crescentic glomerulonephritis, both anti-glomerular basement membrane (GBM) antibodies and anti-neutrophil cytoplasmic antibodies (ANCA) are detected simultaneously. ANCA is presumed to be the initial event but the mechanism is unknown. In the present study, we investigated the antibodies against linear epitopes on Goodpasture autoantigen in sera from patients with ANCA-associated vasculitis, aiming to reveal the mechanisms of the coexistence of the two kinds of autoantibodies...
May 26, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28540889/patterns-of-glomerulonephritis-with-crescents-experience-at-a-tertiary-medical-center-in-saudi-arabia
#2
Turki Al-Hussain, Shuaa Asiri, Sadiq Amer, Hadeel Al Mana, Mohammed Akhtar
A series of 78 cases of glomerulonephritis (GN), in which renal biopsy revealed changes of GN associated with crescent formation, were reviewed. Renal pathology findings were correlated with clinical features including patient's age, renal function, and serologic findings. In most of the cases (71.8%), the crescents were due to immune complex-mediated GN. This was followed by pauci-immune GN (20.5%) and anti-glomerular basement membrane antibody (GBM) GN (7.7%). The percentage of glomeruli with crescents was the highest in cases of anti-GBM disease (mean of 93...
May 2017: Saudi Journal of Kidney Diseases and Transplantation
https://www.readbyqxmd.com/read/28536193/the-ferm-protein-epb41l5-regulates-actomyosin-contractility-and-focal-adhesion-formation-to-maintain-the-kidney-filtration-barrier
#3
Christoph Schell, Manuel Rogg, Martina Suhm, Martin Helmstädter, Dominik Sellung, Mako Yasuda-Yamahara, Oliver Kretz, Victoria Küttner, Hani Suleiman, Laxmikanth Kollipara, René P Zahedi, Albert Sickmann, Stefan Eimer, Andrey S Shaw, Albrecht Kramer-Zucker, Mariko Hirano-Kobayashi, Takaya Abe, Shinichi Aizawa, Florian Grahammer, Björn Hartleben, Jörn Dengjel, Tobias B Huber
Podocytes form the outer part of the glomerular filter, where they have to withstand enormous transcapillary filtration forces driving glomerular filtration. Detachment of podocytes from the glomerular basement membrane precedes most glomerular diseases. However, little is known about the regulation of podocyte adhesion in vivo. Thus, we systematically screened for podocyte-specific focal adhesome (FA) components, using genetic reporter models in combination with iTRAQ-based mass spectrometry. This approach led to the identification of FERM domain protein EPB41L5 as a highly enriched podocyte-specific FA component in vivo...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28515361/lupus-and-proliferative-nephritis-are-pad4-independent-in-murine-models
#4
Rachael A Gordon, Jan M Herter, Florencia Rosetti, Allison M Campbell, Hiroshi Nishi, Michael Kashgarian, Sheldon I Bastacky, Anthony Marinov, Kevin M Nickerson, Tanya N Mayadas, Mark J Shlomchik
Though recent reports suggest that neutrophil extracellular traps (NETs) are a source of antigenic nucleic acids in systemic lupus erythematosus (SLE), we recently showed that inhibition of NETs by targeting the NADPH oxidase complex via cytochrome b-245, β polypeptide (cybb) deletion exacerbated disease in the MRL.Faslpr lupus mouse model. While these data challenge the paradigm that NETs promote lupus, it is conceivable that global regulatory properties of cybb and cybb-independent NETs confound these findings...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28515156/anti-glomerular-basement-membrane-disease
#5
Stephen P McAdoo, Charles D Pusey
Anti-glomerular basement membrane (anti-GBM) disease is a rare small vessel vasculitis that affects the capillary beds of the kidneys and lungs. It is an archetypic autoimmune disease, caused by the development of directly pathogenic autoantibodies targeting a well characterized autoantigen expressed in the basement membranes of these organs, although the inciting events that induce the autoimmune response are not fully understood. The recent confirmation of spatial and temporal clustering of cases suggests that environmental factors, including infection, may trigger disease in genetically susceptible individuals...
May 17, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28512641/podocyte-autophagy-a-potential-therapeutic-target-to-prevent-the-progression-of-diabetic-nephropathy
#6
REVIEW
Na Liu, Liuqing Xu, Yingfeng Shi, Shougang Zhuang
Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD), becomes a worldwide problem. Ultrastructural changes of the glomerular filtration barrier, especially the pathological changes of podocytes, lead to proteinuria in patients with diabetes. Podocytes are major components of glomerular filtration barrier, lining outside of the glomerular basement membrane (GBM) to maintain the permeability of the GBM. Autophagy is a high conserved cellular process in lysosomes including impaired protein, cell organelles, and other contents in the cytoplasm...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28509135/renal-limited-vasculitis-with-elevated-levels-of-multiple-antibodies
#7
Noriaki Sato, Hideki Yokoi, Hirotaka Imamaki, Eiichiro Uchino, Kaoru Sakai, Takeshi Matsubara, Tatsuo Tsukamoto, Sachiko Minamiguchi, Motoko Yanagita
Renal-limited vasculitis (RLV) is a type of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis that presents with crescentic glomerulonephritis with no other organ involvement. Although several studies reported patients with crescentic glomerulonephritis who were dual positive for proteinase 3 (PR3)-ANCA and myeloperoxidase (MPO)-ANCA or ANCA and anti-glomerular basement membrane (GBM) antibody, patients positive for all three antibodies, i.e., triple-positive patients, were rarely reported. We herein report the case of a male with pauci-immune type crescentic glomerulonephritis positive for MPO-ANCA, PR3-ANCA, and anti-GBM antibody...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28509125/a-case-of-pr3-anca-positive-anti-gbm-disease-associated-with-intrarenal-arteritis-and-thrombotic-microangiopathy
#8
Shun Manabe, Mayuko Banno, Marie Nakano, Teruhiro Fujii, Yukio Kakuta, Kosaku Nitta, Michiyasu Hatano
Coexistence of anti-glomerular basement membrane (anti-GBM) disease with anti-neutrophil cytoplasmic antibody (ANCA) is occasionally reported and termed "double positive" disease. Interestingly, the majority of "double positive" ANCA is myeloperoxidase (MPO)-ANCA, and some of the MPO-ANCA-positive cases reveal intrarenal arteritis indicating an ANCA-associated renal lesion. In contrast, proteinase 3 (PR3)-ANCA-positive "double positive" disease had rarely been reported, and as far as we know, none of the cases showed intrarenal arteritis...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28509118/anti-glomerular-basement-membrane-disease-accompanied-by-systemic-lupus-erythematosus-presenting-central-nervous-system-involvement
#9
Hirohito Sugawara, Hideki Takizawa, Yoshinosuke Shimamura, Norihito Moniwa, Koichi Hasegawa, Yayoi Ogawa
We report a case of rapidly progressive glomerulonephritis caused by anti-glomerular basement membrane (GBM) disease accompanied by systemic lupus erythematosus (SLE) presenting central nervous system involvement in a 32-year-old Japanese male. He was admitted to our hospital because of a 3-week history of fever and rapidly failing renal function requiring hemodialysis (HD). Laboratory tests showed anti-GBM antibody elevation with a value of 16,385 units/ml. On day 85, he had generalized tonic-clonic seizure...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28501303/potential-relevance-of-shear-stress-for-slit-diaphragm-and-podocyte-function
#10
Wilhelm Kriz, Kevin V Lemley
Filtrate flow through the glomerular barrier produces shear stresses that tend to disconnect podocytes from the glomerular basement membrane. Forces are highest within the filtration slits. The slit diaphragm mechanically balances the lateral components of the shear stresses on opposing foot processes, preventing widening of the slit.
June 2017: Kidney International
https://www.readbyqxmd.com/read/28490956/changes-in-the-nf%C3%AE%C2%BAb-and-e-cadherin-expression-are-associated-to-diabetic-nephropathy-inpsammomys-obesus
#11
Djamila Aroune, Farid Libdiri, Sophie Leboucher, Boubekeur Maouche, Sergio Marco, Salima El-Aoufi
Diabetes mellitus is a major leading cause of end-stage renal failure, characterized by kidney inflammation and glomerular dysfunction, in worldwide. Kidney inflammation is associated to modifications in the expression levels of pro-inflammatory molecules, such as nuclear factor-κB (NFκB) and adhesion molecules, such as E-cadherin, leading to glomerular dysfunction. However, the relationships between these two processes in human diabetic nephropathy remain an open question. Since Psammomys obesus is an ideal animal model to study diabetes mellitus temporal evolution, we have used this model to study the correlation between kidney structural changes and modification on the expression levels of NFκB and E-cadherin over time...
May 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28490695/-effect-of-hydrogen-sulfide-on-inducible-nitric-oxide-synthase-in-kidneys-of-type-1-diabetic-rats
#12
Rui Yang, Qiang Jia, Shanfeng Ma, Shujun Cui, Xiaofen Liu, Yuanyuan Wang, Qin Gao
To investigate effects of hydrogen sulfide (H2S) on inducible nitric oxide synthase (iNOS) in kidneys of Type 1 diabetic rats.
 Methods: Thirty-two male SD rats were randomly divided into four groups: A normal control (NC) group, a diabetes mellitus (DM) group, a NaHS (NaHS+DM) group, and a NaHS control (NaHS) group (n=8 per group). Type 1 diabetes was induced by a single intraperitoneal injection of streptozotocin (55 mg/kg). After successful establishment of models, the rats in NaHS+DM and NaHS groups were injected with NaHS solution (56 μmol/kg) intraperitoneally...
April 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28483380/rac1-activation-in-podocytes-induces-the-spectrum-of-nephrotic-syndrome
#13
Richard Robins, Cindy Baldwin, Lamine Aoudjit, Jean-François Côté, Indra R Gupta, Tomoko Takano
Hyper-activation of Rac1, a small GTPase, in glomerular podocytes has been implicated in the pathogenesis of familial proteinuric kidney diseases. However, the role of Rac1 in acquired nephrotic syndrome is unknown. To gain direct insights into this, we generated a transgenic mouse model expressing a doxycycline-inducible constitutively active form of Rac1 (CA-Rac1) in podocytes. Regardless of the copy number, proteinuria occurred rapidly within five days, and the histology resembled minimal change disease...
May 5, 2017: Kidney International
https://www.readbyqxmd.com/read/28476557/podocytes-regulate-the-glomerular-basement-membrane-protein-nephronectin-by-means-of-mir-378a-3p-in-glomerular-diseases
#14
Janina Müller-Deile, Jan Dannenberg, Patricia Schroder, Meei-Hua Lin, Jeffrey H Miner, Rongjun Chen, Jan-Hinrich Bräsen, Thomas Thum, Jenny Nyström, Lynne Beverly Staggs, Hermann Haller, Jan Fiedler, Johan M Lorenzen, Mario Schiffer
The pathophysiology of many proteinuric kidney diseases is poorly understood, and microRNAs (miRs) regulation of these diseases has been largely unexplored. Here, we tested whether miR-378a-3p is a novel regulator of glomerular diseases. MiR-378a-3p has two predicted targets relevant to glomerular function, the glomerular basement membrane matrix component, nephronectin (NPNT), and vascular endothelial growth factor VEGF-A. In zebrafish (Danio rerio), miR-378a-3p mimic injection or npnt knockdown by a morpholino oligomer caused an identical phenotype consisting of edema, proteinuria, podocyte effacement, and widening of the glomerular basement membrane in the lamina rara interna...
May 2, 2017: Kidney International
https://www.readbyqxmd.com/read/28469165/the-regulatory-t-cell-transcription-factor-foxp3-protects-against-crescentic-glomerulonephritis
#15
Chen Yang, Xiao-Ru Huang, Erik Fung, Hua-Feng Liu, Hui-Yao Lan
Regulatory T cells (Tregs) have been shown to play a protective role in glomerulonephritis (GN) and Foxp3 is a master transcription factor in Treg development. In this study, we examined the functional role and mechanisms of Foxp3 in a mouse model of accelerated anti-glomerular basement membrane (anti-GBM) GN induced in antigen-primed Foxp3 transgenic (Tg) mice. Compared with littermate of wildtype (WT) mice in which induced severe crescentic GN developed with progressive renal dysfunction, Foxp3 Tg mice had reduced crescent formation, urinary protein excretion, plasma creatinine and decline in creatinine clearance...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28459999/diagnostic-and-management-challenges-in-goodpasture-s-anti-glomerular-basement-membrane-disease
#16
Scott R Henderson, Alan D Salama
Goodpasture's or anti-glomerular basement membrane (GBM) disease is classically characterized by the presence of circulating autoantibodies directed against the non-collagenous domain of the α3 chain of type IV collagen, targeting glomerular and alveolar basement membranes, and associated with rapidly progressive crescentic glomerulonephritis, with alveolar haemorrhage in over half the patients. However, there are increasing examples of variants or atypical presentations of this disease, and novel therapeutic options have been proposed, which nephrologists should be aware of...
April 28, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28457424/what-can-we-do-when-all-collapses-fatal-outcome-of-collapsing-glomerulopathy-and-systemic-lupus-erythematosus-with-diffuse-alveolar-hemorrhage-case-report
#17
H Pinto, R Leal, L Rodrigues, L Santos, C Romãozinho, F Macário, R Alves, J Pratas, V Sousa, C Marinho, L Prado E Castro, F Costa, M Campos, A Mota, A Figueiredo
INTRODUCTION: Collapsing glomerulopathy (CG) is a rare form of glomerular injury. Although commonly associated with human immunodeficiency virus (HIV) infection, it can occur in association with systemic lupus erythematosus (SLE). CASE REPORT: We present the case of a 50-year-old man, with chronic kidney disease secondary to focal and segmental glomerulosclerosis, who received a cadaveric kidney transplant in 2007. There were no relevant intercurrences until May 2015, when he presented with nephrotic range proteinuria (± 4 g/d)...
May 2017: Transplantation Proceedings
https://www.readbyqxmd.com/read/28428258/deletion-of-inositol-requiring-enzyme-1%C3%AE-in-podocytes-disrupts-glomerular-capillary-integrity-and-autophagy
#18
Daniel Robert Kaufman, Joan Papillon, Louise Larose, Takao Iwawaki, Andrey V Cybulsky
Inositol-requiring enzyme-1α (IRE1α) is an endoplasmic reticulum (ER)-transmembrane endoribonuclease-kinase, which plays an essential function in extraembryonic tissues during normal development, and is activated during ER stress. To address the functional role of IRE1α in glomerular podocytes, we produced podocyte-specific IRE1α deletion mice. In male mice, deletion of IRE1α in podocytes resulted in albuminuria beginning at 5 months of age, and worsening with time. Electron microscopy revealed focal podocyte foot process effacement in 9-month old male IRE1α deletion mice, as well as microvillous transformation of podocyte plasma membranes...
April 20, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28424209/the-sulfilimine-cross-link-of-collagen-iv-contributes-to-kidney-tubular-basement-membrane-stiffness
#19
Gautam Bhave, Selene Colon, Nicholas Ferrell
Basement membranes (BMs) are a specialized form of extracellular matrix (ECM) which underlie nearly all cell layers and provide structural support for tissues and interact with cell surface receptors to determine cell behavior. Both macromolecular composition and stiffness of BM influence cell-BM interactions. Collagen IV is major constituent of BM that forms an extensively cross-linked oligomeric network. Its deficiency leads to BM mechanical instability as observed with glomerular basement membrane (GBM) in Alport Syndrome...
April 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28419296/urinary-podocyte-and-tgf-%C3%AE-1-mrna-as-markers-for-disease-activity-and-progression-in-anti-glomerular-basement-membrane-nephritis
#20
Akihiro Fukuda, Akihiro Minakawa, Yuji Sato, Takashi Iwakiri, Shuji Iwatsubo, Hiroyuki Komatsu, Masao Kikuchi, Kazuo Kitamura, Roger C Wiggins, Shouichi Fujimoto
Background.: Podocyte depletion causes glomerulosclerosis, with persistent podocyte loss being a major factor driving disease progression. Urinary podocyte mRNA is potentially useful for monitoring disease progression in both animal models and in humans. To determine whether the same principles apply to crescentic glomerular injury, a rat model of anti-glomerular basement membrane (anti-GBM) nephritis was studied in parallel with a patient with anti-GBM nephritis. Methods...
April 17, 2017: Nephrology, Dialysis, Transplantation
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