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TUBULOINTERSTITIAL

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https://www.readbyqxmd.com/read/28647002/natural-killers-the-bad-guys-in%C3%A2-fibrosis
#1
Jan-Eric Turner
Immune cells infiltrating the tubulointerstitium critically contribute to the progression of chronic kidney disease. In this issue of Kidney international, Law et al. provide first evidence for a role of natural killer cells in the perpetuation of tubulointerstitial fibrosis in human renal disease. By detailed flow cytometric characterization of leukocytes isolated from kidney biopsies of chronic kidney disease patients, they define accumulation of natural killer cells as a feature of fibrotic kidney tissue and provide insight into potential mechanisms of how these cells might promote chronic kidney inflammation...
July 2017: Kidney International
https://www.readbyqxmd.com/read/28642464/serum-c3-and-renal-outcome-in-patients-with-primary-focal-segmental-glomerulosclerosis
#2
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/28628381/monoclonal-immunoglobulin-associated-proliferative-glomerulonephritis-characterized-by-organized-deposits-of-striated-ultra-substructures-a-case-report
#3
Shigeo Hara, Hiroyasu Tsukaguchi, Tastufumi Oka, Makiko Kusabe, Masayuki Mizui, Kensuke Joh
We herein report the case of a 64-year-old male who presented with progressive glomerulonephritis notable for organized and striated ultra-substructures. The patient was diagnosed with hypertension and proteinuria 3 years prior to admission and subsequently developed nephrotic syndrome and impairment of renal function. Laboratory tests did not reveal any evidence of infections or autoimmune diseases. Monoclonal gammopathy was not detected in serum or urine, although a small population of abnormal plasma cell clones was detected by flow cytometry...
June 19, 2017: Ultrastructural Pathology
https://www.readbyqxmd.com/read/28626343/anti-osm-antibody-inhibits-tubulointerstitial-lesion-in-a-murine-model-of-lupus-nephritis
#4
Qingjuan Liu, Yunxia Du, Kejun Li, Wei Zhang, Xiaojuan Feng, Jun Hao, Hongbo Li, Shuxia Liu
The purpose of this study was to investigate the role of oncostatin M (OSM) in tubulointerstitial lesion (TIL) in lupus nephritis (LN). We found that OSM was highly expressed in the renal tissue of LN mice. OSM is one of the interleukin-6 cytokine family members. In order to clarify the role and mechanism of OSM in LN, mice with LN were treated with anti-OSM antibody or isotype antibody. We evaluated the tubular epithelial-mesenchymal transdifferentiation (EMT) by detecting the E-cadherin, α-smooth muscle actin (α-SMA), and fibronectin (FN) expression...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28626027/selective-activation-of-epidermal-growth-factor-receptor-in-renal-proximal-tubule-induces-tubulointerstitial-fibrosis
#5
Jessica M Overstreet, Yinqiu Wang, Xin Wang, Aolei Niu, Leslie S Gewin, Bing Yao, Raymond C Harris, Ming-Zhi Zhang
Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of diabetic nephropathy and renal fibrosis; however, the causative role of sustained EGFR activation is unclear. Here, we generated a novel kidney fibrotic mouse model of persistent EGFR activation by selectively expressing the EGFR ligand, human heparin-binding EGF-like growth factor (HB-EGF), in renal proximal tubule epithelium. Human HB-EGF expression increased tyrosine kinase phosphorylation of EGFR and the subsequent activation of downstream signaling pathways, including ERK and AKT, as well as the profibrotic TGF-β1/SMAD pathway...
June 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28624980/emerging-biomarkers-of-chronic-kidney-disease-in-children
#6
REVIEW
Jason H Greenberg, Aadil Kakajiwala, Chirag R Parikh, Susan Furth
Chronic kidney disease (CKD) has become a significant public health concern, as it is associated with substantial morbidity. Prior research has evaluated multiple novel CKD biomarkers to supplement serum creatinine and proteinuria. The ultimate goal of this research is to find biomarkers that can be used to accurately predict CKD progression and to better time outpatient follow-up, and referral for transplant. Also, an optimal panel of biomarkers can augment the predictive value of proteinuria and serum creatinine by enriching patient enrollment in clinical trials...
June 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28624373/acute-tubulointerstitial-nephritis-in-an-hla-b27-positive-patient-with-axial-spondyloarthritis-being-treated-with-adalimumab
#7
David Castro Corredor, María Dolores Sánchez de la Nieta, Isabel María de Lara Simón
Antagonists of tumor necrosis factor-alpha (ATNF) are used for the treatment of multiple diseases such as psoriatic arthritis, Crohn's disease, ankylosing spondylitis and juvenile idiopathic arthritis, usually, when they are refractory to first-line treatment(1). The use of ATNF has been associated with the induction of autoimmune diseases such as systemic lupus erythematosus-like disease, vasculitis, sarcoidosis-like diseases and, recently, acute granulomatous tubulointerstitial nephritis. We report a case of acute nongranulomatous tubulointerstitial nephritis in an HLA-B27-positive patient with axial spondyloarthritis and Crohn's disease being treated with adalimumab...
June 14, 2017: Reumatología Clinica
https://www.readbyqxmd.com/read/28618421/identification-of-tisp40-as-an-essential-regulator-of-renal-tubulointerstitial-fibrosis-via-tgf-%C3%AE-smads-pathway
#8
Cheng-Cheng Xiao, Jie Zhang, Peng-Cheng Luo, Cong Qin, Yang Du, Jin-Zhuo Ning, Hai-Zhou Zheng
BACKGROUND: Tisp40, a transcription factor of the CREB/CREM family, is involved in cell proliferation, differentiation and other biological functions, but its role in renal tubulointerstitial fibrosis is unknown. METHODS: In our study, we investigated the effects of Tisp40 on extracellular matrix (ECM) accumulation, epithelial-mesenchymal transition (EMT) and the underlying molecular mechanisms in transforming growth factor-β (TGF-β)-stimulated TCMK-1 cells by quantitative real-time polymerase chain reaction (qPCR), Western blot analysis and immunofluorescence in vitro, and further explored the role of Tisp40 on renal fibrosis induced by ischemia-reperfusion (I/R) by qPCR, Western blot analysis, hydroxyproline analysis, Masson trichrome staining and immunohistochemistry staining in vivo...
June 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28615647/differential-synchrotron-x-ray-imaging-markers-based-on-the-renal-microvasculature-for-tubulointerstitial-lesions-and-glomerulopathy
#9
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
https://www.readbyqxmd.com/read/28614243/different-types-of-glomerulonephritis-associated-with-the-dysregulation-of-the-complement-alternative-pathway-in-2-brothers-a-case-report
#10
Pei Chen, Li Zhu, Feng Yu, Sha-Sha Han, Si-Jun Meng, Wei-Yi Guo, Hong Zhang, Yan Song
RATIONALE: C3 glomerulonephritis (C3GN) and complement-mediated hemolytic uremic syndrome (HUS) both result from the abnormal regulation of the complement system. A significant number of patients with C3GN or complement-mediated HUS have mutations of more than 1 complement protein. This discovery has had a major impact on identifying the underlying cause of familial C3GN or complement-mediated HUS. PATIENT CONCERNS: We report the cases of 2 brothers (herein referred to as patient II-1 and patient II-9), both with complement disorders that differed in their clinical and genetic features...
June 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28611663/epigenetic-modifications-to-h3k9-in-renal-tubulointerstitial-cells-after-unilateral-ureteric-obstruction-and-tgf-%C3%AE-1-stimulation
#11
Timothy D Hewitson, Stephen G Holt, Sven-Jean Tan, Belinda Wigg, Chrishan S Samuel, Edward R Smith
Introduction: Epigenetic regulation of fibrogenesis through post-translational histone modifications (marks) may be a key determinant of progression in renal disease. In this study, we examined the distribution and acquisition of histone 3 Lysine 9 (H3K9) marks after injury and stimulation with the pro-fibrotic cytokine TGF-β1. Our focus was on their presence in activated fibroblasts (myofibroblasts) and epithelial cells (epithelial-mesenchymal transition). Methods and Results: Immunofluorescent microscopy was used to examine global H3K9 acetylation (H3K9Ac) and tri-methylation (H3K9Me3) after unilateral ureteric obstruction (UUO) in mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28611350/fgf23-is-synthesised-locally-by-renal-tubules-and-activates-injury-primed-fibroblasts
#12
Edward R Smith, Sven-Jean Tan, Stephen G Holt, Tim D Hewitson
In kidney disease, higher circulating levels of the mineral-regulating hormone fibroblast growth factor (FGF)-23 are predictive of disease progression but direct pathogenic effects on the kidney are unknown. We sought evidence of local renal synthesis in response to unilateral ureteric obstruction in the mouse, and pro-fibrotic actions of FGF23 on the fibroblast in vitro. Acute tubulointerstitial injury due to unilateral ureteric obstruction stimulated renal FGF23 synthesis by tubules, and downregulated inactivating proprotein convertases, without effects on systemic mineral metabolism...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28610763/inflammatory-cell-infiltration-and-resolution-of%C3%A2-kidney-inflammation-is-orchestrated-by-the-cold-shock-protein-y-box-binding-protein-1
#13
Anja Bernhardt, Alexander Fehr, Sabine Brandt, Saskia Jerchel, Tobias M Ballhause, Lars Philipsen, Saskia Stolze, Robert Geffers, Honglei Weng, Klaus-Dieter Fischer, Berend Isermann, Monika C Brunner-Weinzierl, Arvind Batra, Britta Siegmund, Cheng Zhu, Jonathan A Lindquist, Peter R Mertens
Tubular cells recruit monocytic cells in inflammatory tubulointerstitial kidney diseases. The cell-cell communication that establishes pro- or anti-inflammatory activities is mainly influenced by cytokines, reactive oxygen species, nitric oxide, and phagocytosis. Key proteins orchestrating these processes such as cold-shock proteins linked with chemoattraction and cell maturation have been identified. The prototypic member of the cold-shock protein family, Y-box binding protein (YB)-1, governs specific phenotypic alterations in monocytic cells and was explored in the present study...
June 11, 2017: Kidney International
https://www.readbyqxmd.com/read/28605509/a-novel-homozygous-umod-mutation-reveals-gene-dosage-effects-on-uromodulin-processing-and-urinary-excretion
#14
Noel Edwards, Eric Olinger, Jennifer Adam, Michael Kelly, Guglielmo Schiano, Simon A Ramsbottom, Richard Sandford, Olivier Devuyst, John A Sayer
Heterozygous mutations in UMOD encoding the urinary protein uromodulin are the most common genetic cause of autosomal dominant tubulointerstitial kidney disease (ADTKD). We describe the exceptional case of a patient from a consanguineous family carrying a novel homozygous UMOD mutation (p.C120Y) affecting a conserved cysteine residue within the EGF-like domain III of uromodulin. Comparison of heterozygote and homozygote mutation carriers revealed a gene dosage effect with unprecedented low levels of uromodulin and aberrant uromodulin fragments in the urine of the homozygote proband...
June 10, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28602064/notch-signaling-in-the-collecting-duct-regulates-renal-tubulointerstitial-fibrosis-induced-by-unilateral-ureteral-obstruction-in-mice
#15
Arum Choi, Sun Ah Nam, Wan-Young Kim, Sang Hee Park, Hyang Kim, Chul Woo Yang, Jin Kim, Yong Kyun Kim
Background/Aims: Mind bomb-1 (Mib1) encodes an E3 ubiquitin ligase, which is required for the initiation of Notch signaling. Recently, it was demonstrated that the renal collecting duct plays an important role in renal fibrosis. Here, we investigated the role of Notch signaling in renal fibrosis using conditional knockout mice with the specific ablation of Mib1 in renal collecting duct principal cells. Methods: Mib1-floxed mice (Mib1f/f) were crossed with aquaporin 2 (AQP2)-Cre mice in order to generate principal cell-specific Mib1 knockout mice (Mib1f/f :AQP2-Cre+)...
May 26, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28601117/tubular-urinary-indexes-reliably-distinguish-between-primary-tubulointerstitial-and-primary-glomerular-diseases-in-patients-referred-for-kidney-biopsy
#16
Andrej Škoberne, Špela Borštnar, Nuša Avguštin, Damjan Kovač, Andreja Aleš Rigler, Željka Večerić-Haler, Jernej Pajek, Mladen Krsnik, Nika Kojc, Dušan Ferluga, Jelka Lindič
AIMS: Kidney biopsy remains the gold standard for accurately diagnosing renal diseases. Urinalysis and assessment of renal function are the cornerstones for assessment of patients prior to biopsy. There is significant overlap in the results of routine urine parameters (proteinuria, erythrocyturia, leukocyturia) among different kidney diseases, which hinders the possibility of adequately estimating disease etiology prior to the biopsy. The aim of our study was to assess whether diverse markers of glomerular and tubular proteinuria - urinary albumin, IgG, α-1-microglobulin (α-1-m) and N-acetyl-β-D-glucosaminidase (NAG) - are capable of distinguishing between patients with primary tubulointerstitial (TID) and primary glomerular disease (GLOM)...
June 9, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28597149/the-renal-pathological-findings-in-japanese-hiv-infected-individuals-with-ckd-a-clinical-case-series-from-a-single-center
#17
Masaki Hara, Kumiko Momoki, Masamitsu Ubukata, Akihito Ohta, Akiko Tonooka, Minoru Ando
BACKGROUND: Chronic kidney diseases (CKD) have emerged as a significant cause of morbidity and mortality in patients infected with human immunodeficiency virus (HIV). However, the detailed study of renal pathological findings currently remains unclear in these Japanese patients. METHODS: A retrospective cohort study was undertaken to investigate renal pathological findings between January 1996 and July 2016. Our study included 20 Japanese HIV-infected patients with CKD; 10 cases had undergone renal biopsies, and 10 cases had undergone autopsies, respectively...
June 8, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28592423/remission-of-hematuria-improves-renal-survival-in-iga-nephropathy
#18
Angel M Sevillano, Eduardo Gutiérrez, Claudia Yuste, Teresa Cavero, Evangelina Mérida, Paola Rodríguez, Ana García, Enrique Morales, Cristina Fernández, Miguel Angel Martínez, Juan Antonio Moreno, Manuel Praga
Hematuria is a cardinal symptom in IgA nephropathy, but its influence on the risk of disease progression has been scarcely investigated. We followed a cohort of 112 patients with IgA nephropathy for a mean±SEM period of 14±10.2 years, during which clinical and analytic risk factors (including urine sediment examination) were regularly recorded. According to the magnitude of time-averaged hematuria, we classified patients as those with persistent hematuria and those with negative or minimal hematuria. We also classified patients according to the magnitude of time-averaged proteinuria (>0...
June 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28579116/sirt3-prevents-angiotensin-ii-induced-renal-tubular-epithelial-mesenchymal-transition-by-ameliorating-oxidative-stress-and-mitochondrial-dysfunction
#19
Ping He, Zhuoming Li, Zhongbao Yue, Hui Gao, Guoshuai Feng, Panxia Wang, Yi Huang, Wenwei Luo, Huiqi Hong, Liying Liang, Shaorui Chen, Peiqing Liu
Silent mating type information regulation 2 homolog 3 (SIRT3) is a major protective mediator that ameliorates oxidative stress and mitochondrial dysfunction, which are associated with the pathogenesis of epithelial-mesenchymal transition (EMT). The present study was aimed to investigate the potential role of SIRT3 in renal tubular EMT both in vitro and in vivo. Firstly, we showed that the expression of SIRT3 was repressed in angiotensin II-induced EMT. SIRT3 deficiency triggered EMT response, while over-expression of SIRT3 attenuated EMT response...
June 1, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28578628/relationship-between-immunoglobulin-deposition-and-early-lesions-of-progressive-glomerulonephropathy-in-young-common-marmosets
#20
Naoaki Yamada, Nanako Hashimoto, Junichi Kamiie, Takuya Doi, Junko Sato, Takeshi Inoue, Kinji Shirota, Minoru Tsuchitani
The authors previously investigated progressive glomerulonephropathy in 2- to 11-year-old common marmosets and characterized age-related changes of the renal glomeruli and development of tubulointerstitial lesions. In this study, immunoglobulin deposition and ultrastructural changes of the glomeruli were investigated in 5 young marmosets from 6 months to 3 years of age with pre-onset or early glomerulonephropathy. In all animals, the foot processes of podocytes were effaced, and IgM was deposited into the glomeruli...
January 1, 2017: Veterinary Pathology
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