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https://www.readbyqxmd.com/read/28720684/fsgs-as-an-adaptive-response-to-growth-induced-podocyte-stress
#1
Ryuzoh Nishizono, Masao Kikuchi, Su Q Wang, Mahboob Chowdhury, Viji Nair, John Hartman, Akihiro Fukuda, Larysa Wickman, Jeffrey B Hodgin, Markus Bitzer, Abhijit Naik, Jocelyn Wiggins, Matthias Kretzler, Roger C Wiggins
Glomerular sclerotic lesions develop when the glomerular filtration surface area exceeds the availability of podocyte foot process coverage, but the mechanisms involved are incompletely characterized. We evaluated potential mechanisms using a transgenic (podocin promoter-AA-4E-BP1) rat in which podocyte capacity for hypertrophy in response to growth factor/nutrient signaling is impaired. FSGS lesions resembling human FSGS developed spontaneously by 7 months of age, and could be induced earlier by accelerating kidney hypertrophy by nephrectomy...
July 18, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28716959/podocyte-growing-pains-in-adaptive-fsgs
#2
EDITORIAL
Vivette D D'Agati
No abstract text is available yet for this article.
July 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28709595/losing-their-footing-rac1-signaling-causes-podocyte-detachment-and-fsgs
#3
Gentzon Hall, Robert F Spurney
Selective modulation of Rho GTPase activity in podocytes recapitulates characteristic features of human nephrosis. Using a mouse model, Robins et al. found that high levels of Rac1 activation in podocytes caused podocyte detachment and glomerulosclerosis. Podocyte Rac1 activity was enhanced in biopsy specimens from patients with nephrosis, and serum from this patient population activated Rac1 in cultured podocytes. These data provide a causal link between podocyte Rac1 activation and human nephrotic diseases...
August 2017: Kidney International
https://www.readbyqxmd.com/read/28707483/investigational-drugs-in-development-for-focal-segmental-glomerulosclerosis
#4
Howard Trachtman
Focal segmental glomerulosclerosis is an important cause of end stage kidney disease and is a paradigm for the study of glomerular scarring. There are no FDA approved treatments for this condition. Current therapies, assessed based on reduction in proteinuria, are generally effective in a subset of patients which suggests that FSGS is a heterogeneous group of glomerular disorders or podocytopathies that converge on a common histopathological phenotype. Areas covered: We searched for investigational drugs agents that target different pathophysiological pathways using the key words 'FSGS' and 'podocyte' in American and European clinical trial registers (clinicaltrials...
July 14, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28700988/high-dose-rituximab-ineffective-for-focal-segmental-glomerulosclerosis-a-long-term-observation-study
#5
Dario Roccatello, Savino Sciascia, Daniela Rossi, Mirella Alpa, Carla Naretto, Massimo Radin, Antonella Barreca, Roberta Fenoglio, Simone Baldovino, Elisa Menegatti
BACKGROUND: A beneficial effect of rituximab (RTX) on focal segmental glomerulosclerosis (FSGS) in pediatric patients or in transplant recipients has been reported in isolated cases. However, the use of RTX in adult patients with idiopathic FSGS needs further investigation. METHODS: Eight patients who had biopsy-proven FSGS (63.9 ± 14.0, range 40-81 years, 4 women, 4 men) with major risk factors precluding corticosteroids or conventional immunosuppression were treated with a high dose of RTX (8 weekly doses of 375 mg/m2) and prospectively followed up for at least 2 years (29...
July 13, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28696047/a-randomized-trial-of-the-effectiveness-of-the-neutropenic-diet-versus-food-safety-guidelines-on-infection-rate-in-pediatric-oncology-patients
#6
Karen M Moody, Rebecca A Baker, Ruth O Santizo, Inan Olmez, Jeanie M Spies, Amanda Buthmann, Linda Granowetter, Robin Y Dulman, Kanyalakshmi Ayyanar, Jonathan B Gill, Aaron E Carroll
BACKGROUND: The neutropenic diet (ND) is prescribed to avoid introduction of bacteria into a host's gastrointestinal tract and reduce infection. Due to a lack of evidence to support the ND, there continues to be debate among pediatric oncologists regarding its usefulness. This prospective randomized controlled trial evaluated the difference in neutropenic infection rates in pediatric oncology patients randomized to Food and Drug Administration approved food safety guidelines (FSGs) versus the ND plus FSGs during one cycle of chemotherapy...
July 11, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28674043/beneficial-effects-of-systemically-administered-human-muse-cells-in-adriamycin-nephropathy
#7
Nao Uchida, Yoshihiro Kushida, Masaaki Kitada, Shohei Wakao, Naonori Kumagai, Yasumasa Kuroda, Yoshiaki Kondo, Yukari Hirohara, Shigeo Kure, Gregorio Chazenbalk, Mari Dezawa
Multilineage-differentiating stress-enduring (Muse) cells are nontumorigenic endogenous pluripotent-like stem cells that can be collected from various organs. Intravenously administered Muse cells have been shown to spontaneously migrate to damaged tissue and replenish lost cells, but the effect in FSGS is unknown. We systemically administered human bone marrow-derived Muse cells without concurrent administration of immunosuppressants to severe combined immune-deficient (SCID) and BALB/c mouse models with adriamycin-induced FSGS (FSGS-SCID and FSGS-BALB/c, respectively)...
July 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28664408/focal-segmental-glomerulosclerosis-why-does-it-occur-segmentally
#8
REVIEW
Michio Nagata, Namiko Kobayashi, Satoshi Hara
Podocyte loss is the fundamental basis of glomerulosclerosis. Focal segmental glomerulosclerosis (FSGS) is a progressive glomerular disease, and its glomerular features are a prototype of podocyte loss-driven glomerulosclerosis. The glomerular pathology of FSGS is characterized by a focal and segmental location of the sclerotic lesions in human FSGS; segmental sclerosis often shows simultaneous intra- and extra-capillary changes, including parietal cell migration, capillary collapse, hyaline deposition, and intra-capillary thrombi and occasional hypercellularity...
June 29, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28664407/combined-use-of-electron-microscopy-and-intravital-imaging-captures-morphological-and-functional-features-of-podocyte-detachment
#9
REVIEW
James L Burford, Georgina Gyarmati, Isao Shirato, Wilhelm Kriz, Kevin V Lemley, János Peti-Peterdi
The development of podocyte injury and albuminuria in various glomerular pathologies is still incompletely understood due to technical limitations in studying the glomerular filtration barrier (GFB) in real-time. We aimed to directly visualize the early morphological and functional changes of the GFB during the development of focal segmental glomerulosclerosis (FSGS) using a combination of transmission electron microscopy (TEM) and in vivo multiphoton microscopy (MPM) in the rat puromycin aminonucleoside (PAN) model...
June 29, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28663230/tissue-specific-microrna-expression-patterns-in-four-types-of-kidney-disease
#10
Maria Angeles Baker, Seth J Davis, Pengyuan Liu, Xiaoqing Pan, Anna Marie Williams, Kenneth A Iczkowski, Sean T Gallagher, Kaylee Bishop, Kevin R Regner, Yong Liu, Mingyu Liang
MicroRNAs contribute to the development of kidney disease. Previous analyses of microRNA expression in human kidneys, however, were limited by tissue heterogeneity or the inclusion of only one pathologic type. In this study, we used laser-capture microdissection to obtain glomeruli and proximal tubules from 98 human needle kidney biopsy specimens for microRNA expression analysis using deep sequencing. We analyzed specimens from patients with diabetic nephropathy (DN), FSGS, IgA nephropathy (IgAN), membranoproliferative GN (MPGN) (n=19-23 for each disease), and a control group (n=14)...
June 29, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28663063/development-of-focal-segmental-glomerulosclerosis-patient-reported-outcome-measures-symptom-diary-and-symptom-impact-questionnaire
#11
Susan D Mathias, Susan Vallow, Debbie S Gipson, Kevin S Thorneloe, Dennis Sprecher
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a kidney disease that affects patients' functioning and well-being. This study aimed to develop patient-reported outcome questionnaires to measure patient experiences related to FSGS. STUDY DESIGN: Qualitative patient interviews to identify important symptoms and concepts (concept elicitation) formed the basis for the development of 2 questionnaires, one on symptoms and one on their impact. Additional qualitative interviews were implemented to evaluate/refine the questionnaires (cognitive debriefing)...
June 26, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28658768/clinicopathological-analysis-of-glomerular-disease-of-adult-onset-nephrotic-syndrome-in-an-indian-cohort-a-retrospective-study
#12
Mayur Suryawanshi, Swapnil Karnik, Sanjeet Roy
INTRODUCTION: Primary glomerular disease presenting with adult onset nephrotic syndrome are a major cause of chronic renal failure worldwide. The spectrum of renal disease presenting with nephrotic syndrome has undergone a gradual change globally over the course of time. However, there still exist regional differences in the incidence of primary glomerular diseases causing adult onset nephrotic syndrome. AIM: To observe the spectrum of renal diseases presenting with adult onset nephrotic syndrome with comparative analysis of changing trends over the last five decades with regards to Western and Indian literature...
May 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28658762/role-of-immunofluorescence-in-adult-onset-nephrotic-syndrome-a-study-in-a-tertiary-care-centre-of-western-india
#13
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/28658201/targeted-next-generation-sequencing-in-brazilian-children-with-nephrotic-syndrome-submitted-to-renal-transplant
#14
Luciana S Feltran, Patricia Varela, Elton D Silva, Camila L Veronez, Maria C Franco, Alvaro P Filho, Maria F Camargo, Paulo C Koch Nogueira, Joao B Pesquero
BACKGROUND: The aims of this study were to identify the genetic mutations profile in Brazilian children with nephrotic syndrome and to determine a genotype-phenotype correlation in this disease. METHODS: Next generation sequencing (NGS) and mutation analysis were performed on 24 genes related to nephrotic syndrome in a cross-sectional study involving 95 children who underwent kidney transplantation due to nephrotic syndrome, excluding congenital cases. RESULTS: A total of 149 variants were identified in 22 out of 24 sequenced genes...
June 28, 2017: Transplantation
https://www.readbyqxmd.com/read/28646406/podocytes-and-the-quest-for-precision-medicines-for-kidney-diseases
#15
REVIEW
Peter Mundel
In this review, I describe a 30-year journey in the quest for precision medicines for patients with kidney diseases. In 1987, when I started my reseach career, most scientists studying glomerular disease biology were focused on mesangial cells. The crucial role of the podocyte in many kidney diseases characterized by proteinuria, including focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, had not yet been recognized. We were not aware of genetic causes or drivers of kidney diseases nor of molecular markers and cell culture systems for mechanistic studies of podocyte biology...
June 23, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28643120/the-incidence-of-the-nephrotic-syndrome-in-childhood-in-germany
#16
Ingo Franke, Malik Aydin, Corinna Elke Llamas Lopez, Lisa Kurylowicz, Rainer Ganschow, Michael Lentze, Mark Born
BACKGROUND: The incidence of childhood nephrotic syndrome (NS) in Germany is not well known. METHODS: An ESPED-based nationwide collection of epidemiological data of children in 2005 and 2006. RESULT: The mean age of NS at onset was 5.5 ± 3.7 years. The gender ratio of boys to girls was 1.8:1. The average length of stay was 15.5 ± 11.2 days, with younger children remaining significantly longer in hospital. Steroid-resistance was more common in children ≥8 years (p = 0...
June 22, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28642464/serum-c3-and-renal-outcome-in-patients-with-primary-focal-segmental-glomerulosclerosis
#17
Jian Liu, Jingyuan Xie, Xiaoyan Zhang, Jun Tong, Xu Hao, Hong Ren, Weiming Wang, Nan Chen
The role of complement (C) in the pathogenesis or progression of focal segmental glomerulosclerosis (FSGS) is uncertain. The present study assessed the relationship between serum C3, the baseline characteristics, and the progression of FSGS in the cohort and identified the clinical implications of serum C3 levels in patients with FSGS. Compared to the patients with C3 ≥ 85 mg/dL (N = 474), those with C3 < 85 mg/dL (N = 117) presented a higher level of serum creatinine, lower levels of eGFR, hemoglobin, proteinuria, triglyceride, cholesterol, IgA, as well as, severe tubulointerstitial injury (TI)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28630634/moxibustion-alleviates-injury-in-a-rat-focal-segmental-glomerulosclerosis-model
#18
Yi Li, Yuxia Sun, Chunling Zhang, Ke Wang, Peicheng Shen, Di Huang, Wen Ma, Jin Zhang, Lin Li, Liqun He
OBJECTIVES: To evaluate the therapeutic effects of moxibustion at Shenshu (BL-23) and Geshu (BL-17) acupoints in a focal segmental glomerulosclerosis (FSGS) model in rats. METHODS: A FSGS rat model was established by single nephrectomy and repeated injection of doxorubicin. The FSGS rats were randomly divided into the model group, losartan (positive control) group, Shenshu moxibustion group, and Geshu moxibustion group. Molecular indicators of kidney function and renal pathological changes were monitored...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28629718/changes-in-podocyte-trpc-channels-evoked-by-plasma-and-sera-from-patients-with-recurrent-fsgs-and-by-putative-glomerular-permeability-factors
#19
Eun Young Kim, Hila Roshanravan, Stuart E Dryer
Primary forms of focal and segmental glomerulosclerosis (FSGS) are driven by circulating factors that cause dysfunction or loss podocytes. Rare genetic forms of FSGS can be caused by mutations in TRPC6, which encodes a Ca(2+)-permeable cationic channel expressed in mesangial cells and podocytes; and NPHS2, which encodes podocin, a TRPC6-binding protein expressed in podocyte slit diaphragm domains. Here we observed that exposing immortalized mouse podocytes to serum or plasma from recurrent FSGS patients for 24h increased the steady-state cell-surface abundance of TRPC6, accompanied by an increase in currents through endogenous TRPC6 channels evoked by a hypoosmotic stretch stimulus...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28615647/differential-synchrotron-x-ray-imaging-markers-based-on-the-renal-microvasculature-for-tubulointerstitial-lesions-and-glomerulopathy
#20
Yu-Chuan Lin, Yeukuang Hwu, Guo-Shu Huang, Michael Hsiao, Tsung-Tse Lee, Shun-Min Yang, Ting-Kuo Lee, Nan-Yow Chen, Sung-Sen Yang, Ann Chen, Shuk-Man Ka
High resolution synchrotron microtomography capable of revealing microvessels in three dimensional (3D) establishes distinct imaging markers of mouse kidney disease strongly associated to renal tubulointerstitial (TI) lesions and glomerulopathy. Two complementary mouse models of chronic kidney disease (CKD), unilateral ureteral obstruction (UUO) and focal segmental glomerulosclerosis (FSGS), were used and five candidates of unique 3D imaging markers were identified. Our characterization to differentially reflect the altered microvasculature of renal TI lesions and/or glomerulopathy demonstrated these image features can be used to differentiate the disease status and the possible cause therefore qualified as image markers...
June 14, 2017: Scientific Reports
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