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tubular disease

Fang Chen, Zhiqiang Sun, Xiaoguang Zhu, Yali Ma
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. It has been found that astilbin, a flavonoid compound, exerts a protective effect on DN. However, the role of astilbin in autophagy during DN is unknown. The human proximal tubular epithelial cells (HK-2 cells) were treated with high glucose (HG, 30 mM) in the presence or absence of astilbin. Cell viability was measured by MTT assay. The autophagy was determined by detecting the expression of LC3-II and p62 using western blot. The cell apoptosis was evaluated by detecting the apoptosis rate, caspase-3 activity, and the expression of Bcl-2 and Bax...
July 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ling Hou, Yue Du, Chengguang Zhao, Yubin Wu
PURPOSE: We sought to investigate the role of PAX2 in renal epithelial-to-mesenchymal transition (EMT), examining the influence of PAX2 on ADAM10 expression during renal EMT and ADAM10 expression in fibrotic kidneys. METHODS: A rat renal tubular epithelial cell line, NRK52E, was transfected with lentivirus carrying PAX2, and E-cadherin and α-SMA expressions were measured. The influence of PAX2 on ADAM10 promoter activity was evaluated using chromatin immunoprecipitation (CHIP) and dual-luciferase reporter assay...
August 16, 2018: International Urology and Nephrology
Xiaoyi Zhang, Ling Chen
Renal cell carcinoma (RCC) and chronic kidney disease (CKD) are associated with hypoxia, but the effects of hypoxia on the process of angiogenesis in the two diseases are dramatically different. Some of matrix metalloproteinases (MMPs), such as MMP2 and MMP9, may have a role because they represent the most prominent family of proteinases associated with angiogenesis. In the present study, the differential response of human renal cell cancer cells (786-0), human renal tubular epithelial cells (HK-2) and human microvascular endothelial cells (HMEC-1) to hypoxia with regards to the expression of MMP2, MMP9, MMP14, TIMP2, RECK was investigated...
August 2018: Experimental and Therapeutic Medicine
Ji Hye Huh, Minyoung Lee, So Young Park, Jae Hyeon Kim, Byung Wan Lee
BACKGROUND: The aim of this study was to investigate which glycemic parameters better reflect urinary N-acetyl-β-D-glucosaminidase (uNAG) abnormality, a marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM) subjects with normoalbuminuria and a normal estimated glomerular filtration rate (eGFR). METHODS: We classified 1,061 participants with T2DM into two groups according to uNAG level-normal vs. high (>5.8 U/g creatinine)-and measured their biochemical parameters...
May 2, 2018: Diabetes & Metabolism Journal
Mohsen Honarpisheh, Orestes Foresto-Neto, Stefanie Steiger, Franziska Kraft, Paulina Koehler, Ekaterina von Rauchhaupt, Jan Potempa, Karina Adamowicz, Joanna Koziel, Maciej Lech
Acute and chronic kidney injuries are multifactorial traits that involve various risk factors. Experimental animal models are crucial to unravel important aspects of injury and its pathophysiological mechanisms. Translating knowledge obtained from experimental approaches into clinically useful information is difficult; therefore, significant attention needs to be paid to experimental procedures that mimic human disease. Herein, we compared aristolochic acid I (AAI) acute and chronic kidney injury model with unilateral ischemic-reperfusion injury (uIRI), cisplatin (CP)- or folic acid (FA)-induced renal damage...
August 15, 2018: Scientific Reports
Hua Li, Jibo Wang, Xiaoru Liu, Qiang Cheng
During the pathogenetic process of varied kidney diseases, renal tubules are the major sites in response to detrimental insults, including pro-inflammatory stimuli. MicroRNA-204-5p (miR-204-5p) can be detected in the renal tubular epithelial cells in the normal kidney, its expression however is downregulated in the kidney with pathological changes. This study aimed to investigate the role of miR-204-5p in interleukin 6 (IL6)-mediated inflammatory response and chemokine production in HK-2 renal tubular cells...
August 15, 2018: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
Emanuela di Palmo, Marcella Gallucci, Elena Tronconi, Rosalba Bergamaschi, Salvatore Cazzato, Claudio La Scola, Giampaolo Ricci, Andrea Pession
The term osteopetrosis describes a group of rare hereditary diseases of the skeleton, characterized by an increase in bone density, caused by a defect in the development or function of osteoclasts. It comprises a clinically and genetically heterogeneous conditions ranging from infantile onset life-threatening forms to mildest adult onset forms. "Malignant" osteopetrosis is characterized by bone fragility, short stature, compressive neuropathies, hypocalcaemia, pancytopaenia. The deficiency of carbonic anhydrase II causes a moderate form, presenting classically as a triad of osteopetrosis, renal tubular acidosis (RTA), and cerebral calcification...
2018: Frontiers in Pediatrics
Y N Zhao, X T Wang, Q Y Xia, G P Wang, S Y Sun, L F Zhao, X J Zhou, Q Rao
Objective: To study the clinicopathologic features, immunophenotype, characteristic FISH pattern and prognosis of renal cell carcinoma (RCC) associated with chromosome X inversion harboring gene fusions involving TFE3. Methods: Ten cases of NONO-TFE3 RCC and four cases of RBM10-TFE3 RCC were investigated at Nanjing Jinling Hospital from 2009 to 2016 by clinicopathological findings, immunohistochemistry, and genetic analysis. Results: Morphologically, the distinct pattern of secretory endometrioid subnuclear vacuolization was overlapped with clear cell papillary RCC, and often accompanied by sheets of epithelial cells in NONO-TFE3 RCC...
August 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Viktor Rotbain Curovic, Tine W Hansen, Mie K Eickhoff, Bernt Johan von Scholten, Henrik Reinhard, Peter Karl Jacobsen, Frederik Persson, Hans-Henrik Parving, Peter Rossing
AIMS: Urinary levels of kidney injury molecule 1 (u-KIM-1) and neutrophil gelatinase-associated lipocalin (u-NGAL) reflect proximal tubular pathophysiology and have been proposed as risk markers for development of complications in patients with type 2 diabetes (T2D). We clarify the predictive value of u-KIM-1 and u-NGAL for decline in eGFR, cardiovascular events (CVE) and all-cause mortality in patients with T2D and persistent microalbuminuria without clinical cardiovascular disease. METHODS: This is a prospective study that included 200 patients...
August 14, 2018: Acta Diabetologica
Callie Plafkin, Tripti Singh, Brad C Astor, Sandesh Parajuli, Gauri Bhutani, Nasia Safdar, Sarah E Panzer
BACKGROUND: Polyomavirus-associated nephropathy is associated with high risk of kidney allograft loss. Whether the cause of native end-stage renal disease influences the risk of BK infection is unclear. METHODS: A retrospective, single-center study of 2,741 adult kidney transplant recipients between 1994 to 2014 was performed. Recipients had end-stage renal disease due to polycystic kidney disease (PKD, n=549), diabetes mellitus (DM, n=947), hypertension (HTN, n=442), or glomerulonephritis (GN, n=803)...
August 13, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Hiroyuki Ueda, Yoichi Miyazaki, Nobuo Tsuboi, Keita Hirano, Shinya Yokote, Emi Kobayashi, Makoto Ogura, Tetsuya Kawamura, Munekazu Ryuzaki, Takashi Yokoo
Objective This case series aimed to identify the clinical and pathological characteristics of elderly patients (≥60 years) with biopsy-proven IgA vasculitis with nephritis (IgAVN). Methods The clinical and pathological presentation and treatment outcomes were compared between two groups. Patients Patients with IgAVN who were ≥19 years old at the time of their renal biopsy were divided into elderly (≥60 years) and adult (19-59 years) groups. Results Of the 23 patients in our study, 13 were elderly. In the elderly group, the median age at the diagnosis was 68 years (range, 60-85 years), with a median follow-up period of 15 months (range, 3-80 months)...
August 10, 2018: Internal Medicine
Seiji Kishi, Fumiaki Obata, Hirokazu Miki, Motokazu Matsuura, Kenji Nishimura, Masanori Tamaki, Fumi Kishi, Taichi Murakami, Hideharu Abe, Kojiro Nagai, Masahiro Abe, Toshio Doi
Light Chain Proximal Tubulopathy (LCPT) is a rare form of paraprotein-related kidney disease in which monoclonal free light chains damage the proximal renal tubular epithelial cells. We herein report the case of a 78-year-old woman who presented with anemia and kidney dysfunction. Serum and urine protein electrophoresis analyses revealed a monoclonal IgD and λ free light chains. Proximal tubular injury and the accumulation of λ light chains were found by kidney biopsy. Electron microscopy revealed no organized structure suggestive of crystals...
August 10, 2018: Internal Medicine
Yan Zhang, Xiaoli Su, Fangfang Zou, Tengjuan Xu, Pinhua Pan, Chengping Hu
BACKGROUND: Obstructive sleep apnea (OSA)-associated chronic kidney disease is mainly caused by chronic intermittent hypoxia (CIH) triggered renal damage. This study aims to investigate the role of toll-like receptor-4 (TLR4) in underlying mechanism involved chronic intermittent hypoxia (CIH)-induced renal damage. METHODS: C57BL/6J mice with normal TLR4 (TLR4 WT) or deficient TLR4 (TLR4 KO) were divided into four groups and exposed to normal air (NA) and CIH: TLR4 WT + NA, TLR4 KO + NA, TLR4 WT + CIH, and TLR4 KO + CIH...
August 11, 2018: Sleep & Breathing, Schlaf & Atmung
Sun-Ji Park, Yeawon Kim, Ying Maggie Chen
The advent of next-generation sequencing (NGS) in recent years has led to a rapid discovery of novel or rare genetic variants in human kidney cell genes, which is transforming the risk assessment, diagnosis, and treatment of kidney disease. Mutations may lead to protein misfolding, disruption of protein trafficking, and endoplasmic reticulum (ER) retention. An imbalance between the load of misfolded proteins and the folding capacity of the ER causes ER stress and unfolded protein response. Mutations in nephrin (NPHS1), podocin (NPHS2), laminin β2 (LAMB2), and α-actinin-4 (ACTN4) have been shown to induce ER stress in HEK293 cells and podocytes in hereditary nephrotic syndromes; various founder mutations in collagen IV α chains (COL4A) have been demonstrated to activate podocyte ER stress in collagen IV nephropathies; and mutations in uromodulin (UMOD) have been reported to trigger tubular ER stress in autosomal dominant tubulointerstitial kidney disease...
August 11, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Debra Dorotea, Guideock Kwon, Jung Hwa Lee, Erika Saunders, Yun Soo Bae, Sung Hwan Moon, Soo Jin Lee, Dae Ryong Cha, Hunjoo Ha
BACKGROUND: NADPH oxidases (Nox) is a major enzyme system contributing to oxidative stress, which plays an important role in the pathogenesis of diabetic kidney disease (DKD). We have shown an elevation of renal Nox1, Nox2, and Nox4 in diabetic mice. APX-115, a pan-Nox inhibitor, attenuated the progression of DKD in mice. As the standard diabetic mice cannot fully mimic human DKD, the present study was aimed to show the dose-dependent effect and to provide a confirmatory evidence of APX-115 in attenuating DKD in diabetic rats...
August 10, 2018: Pharmacology
Siu Chiu Chan, Ying Zhang, Annie Shao, Svetlana Avdulov, Jeremy Herrera, Karam Aboudehen, Marco Pontoglio, Peter Igarashi
BACKGROUND: Mutation of HNF1B , the gene encoding transcription factor HNF-1 β , is one cause of autosomal dominant tubulointerstitial kidney disease, a syndrome characterized by tubular cysts, renal fibrosis, and progressive decline in renal function. HNF-1 β has also been implicated in epithelial-mesenchymal transition (EMT) pathways, and sustained EMT is associated with tissue fibrosis. The mechanism whereby mutated HNF1B leads to tubulointerstitial fibrosis is not known. METHODS: To explore the mechanism of fibrosis, we created HNF-1 β -deficient mIMCD3 renal epithelial cells, used RNA-sequencing analysis to reveal differentially expressed genes in wild-type and HNF-1 β -deficient mIMCD3 cells, and performed cell lineage analysis in HNF-1 β mutant mice...
August 10, 2018: Journal of the American Society of Nephrology: JASN
Qiyuan Li, Boyue Lian, Yuan Wang, Robert A Taylor, Michelle Dong, Tracey Lloyd, Xuefei Liu, Joel Tan, Md Mahfuz Ashraf, Divyang Waghela, Gregory Leslie
The consumption of saline groundwater has contributed to a growing incidence of renal diseases, particularly in coastal communities of India. Although reverse osmosis (RO) is routinely used to remove salt from groundwater, conventional RO systems (i.e. centralized systems using spiral wound RO elements) have limited utility in these communities due to high capital and maintenances costs, and lack of infrastructure to distribute the water. Consequently, there is a need to develop an appropriate solution for groundwater treatment based on small-scale, mobile and community-led systems...
August 2, 2018: Water Research
Carlos G Musso, Alejandrina Castañeda, María Giordani, Cesar Mombelli, Silvia Groppa, Nora Imperiali, Guillermo Rosa Diez
Kidney transplant patients (KTPs), and particularly those with advanced chronic kidney rejection, may be affected by opportunistic infections, metabolic alterations and vascular and oncologic diseases that promote clinical conditions that require a variety of treatments, the combinations of which may predispose them to hyponatremia. Salt and water imbalance can induce abnormalities in volemia and/or serum sodium depending on the nature of this alteration (increase or decrease), its absolute magnitude (mild or severe) and its relative magnitude (body sodium:water ratio)...
August 2018: Clinical Kidney Journal
Nikit Kumar, Marianna Leonzino, William Hancock-Cerutti, Florian A Horenkamp, PeiQi Li, Joshua A Lees, Heather Wheeler, Karin M Reinisch, Pietro De Camilli
Mutations in the human VPS13 genes are responsible for neurodevelopmental and neurodegenerative disorders including chorea acanthocytosis (VPS13A) and Parkinson's disease (VPS13C). The mechanisms of these diseases are unknown. Genetic studies in yeast hinted that Vps13 may have a role in lipid exchange between organelles. In this study, we show that the N-terminal portion of VPS13 is tubular, with a hydrophobic cavity that can solubilize and transport glycerolipids between membranes. We also show that human VPS13A and VPS13C bind to the ER, tethering it to mitochondria (VPS13A), to late endosome/lysosomes (VPS13C), and to lipid droplets (both VPS13A and VPS13C)...
August 9, 2018: Journal of Cell Biology
Lili Zhou, Shan Zhou, Peng Yang, Yuan Tian, Zhiwei Feng, Xiang-Qun Xie, Youhua Liu
The cannabinoid receptor type 2 (CB2) is a G protein-coupled seven transmembrane receptor that transmits endogenous cannabinoid signaling. The role of CB2 in the pathogenesis of kidney injury and fibrosis remains poorly understood. Here we demonstrate that CB2 was induced, predominantly in kidney tubular epithelium, in various models of kidney disease induced by unilateral ureteral obstruction, adriamycin or ischemia/reperfusion injury. In vitro, forced expression of CB2 or treatment with a CB2 agonist was sufficient to trigger matrix gene expression, whereas knockdown of CB2 by siRNA abolished transforming growth factor-β1-induced signaling and fibrogenic responses in kidney tubular cells...
August 6, 2018: Kidney International
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