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tubular disease

Shuyun Liu, Meng Zhao, Yijie Zhou, Chengshi Wang, Yujia Yuan, Lan Li, William Bresette, Younan Chen, Jingqiu Cheng, Yanrong Lu, Jingping Liu
BACKGROUND: Renal fibrosis is the pathological feature of chronic kidney disease (CKD) which leads to end-stage renal disease (ESRD) and renal failure. Resveratrol [3,5,4'-trihydroxy-trans-stilbene (RSV)] has shown benefits for metabolic diseases and anti-cancer therapy, but its potential risk on renal health has not been fully evaluated. PURPOSE: To investigate the global effects of RSV on renal fibrosis in human tubular epithelial cell (TEC) line HK-2, and in mice with unilateral ureteral obstruction (UUO)...
December 17, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Jung-Soon Mo, Dabin Choi, Yu-Ran Han, Nambin Kim, Han-Sol Jeong
ER stress is an early event of acute kidney injury and has been linked to accelerate the development of chronic kidney disease. Therefore, the compounds that can mimic ER stress inhibitor may confer regulatory effects on ER stress induced apoptosis. In this study, we investigated the protective effects of flavonoid morin against ER stress induced apoptosis in human renal proximal tubular HK-2 cells. Morin downregulated the expression of GRP78, central regulator of ER stress response, induced by ER stress inducer tunicamycin...
February 19, 2019: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Joshua Rowland, Artur Akbarov, James Eales, Xiaoguang Xu, John P Dormer, Hui Guo, Matthew Denniff, Xiao Jiang, Parisa Ranjzad, Alicja Nazgiewicz, Priscilla Ribeiro Prestes, Andrzej Antczak, Monika Szulinska, Ingrid A Wise, Ewa Zukowska-Szczechowska, Pawel Bogdanski, Adrian S Woolf, Nilesh J Samani, Fadi J Charchar, Maciej Tomaszewski
Nephrons scar and involute during aging, increasing the risk of chronic kidney disease. Little is known, however, about genetic mechanisms of kidney aging. We sought to define the signatures of age on the renal transcriptome using 563 human kidneys. The initial discovery analysis of 260 kidney transcriptomes from the TRANScriptome of renaL humAn TissuE Study (TRANSLATE) and the Cancer Genome Atlas identified 37 age-associated genes. For 19 of those genes, the association with age was replicated in 303 kidney transcriptomes from the Nephroseq resource...
March 2019: Kidney International
Letizia De Chiara, Paola Romagnani
Tubulointerstitial fibrosis is considered a hallmark of maladaptive repair processes after tubular injury leading to chronic kidney disease. Nakamura and colleagues show that, upon injury, myofibroblasts promote epithelial repair by producing retinoic acid in place of injured tubular cells. These results suggest that resident fibroblasts turning into myofibroblasts maintain a cross-talk that protects tubular epithelial cells from injury and can restore tissue integrity and functionality, challenging the concept that fibrosis is only detrimental in nature...
March 2019: Kidney International
N Tokuzen, H Goda, K Nakashiro
Mammary analogue secretory carcinoma (MASC) has recently been recognized as a salivary gland tumour that is characterized by the ETV6-NTRK3 fusion gene. A case of locally advanced MASC of the parotid gland in a 67-year-old man is presented here. The patient visited the hospital due to a large right infra-auricular mass, which had been enlarging gradually over a period of 2years. Contrast-enhanced computed tomography (CT) demonstrated a multilocular mass, 75×63mm in size, containing a fluid component with non-uniform contrast effects in the interior portion...
February 15, 2019: International Journal of Oral and Maxillofacial Surgery
Nahid Tabibzadeh, Sandra Wagner, Marie Metzger, Martin Flamant, Pascal Houillier, Jean-Jacques Boffa, Francois Vrtovsnik, Eric Thervet, Bénédicte Stengel, Jean-Philippe Haymann
RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD)...
February 15, 2019: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Zinan Yin, Juan Du, Fan Yu, Weibo Xia
Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption, with a low or inappropriately normal level of active vitamin D. The culprit tumors of TIO could produce fibroblast growth factor 23 which plays a role in regulating renal Pi handling and 25-hydroxyvitamin D 1α-hydroxylase activity. Chronic hypophosphatemia could eventually lead to inadequate bone mineralization, presenting as osteomalacia...
December 2018: Osteoporosis and Sarcopenia
Sergio Camilo Lopez-Garcia, Francesco Emma, Stephen B Walsh, Marc Fila, Nakysa Hooman, Marcin Zaniew, Aurélia Bertholet-Thomas, Giacomo Colussi, Kathrin Burgmaier, Elena Levtchenko, Jyoti Sharma, Jyoti Singhal, Neveen A Soliman, Gema Ariceta, Biswanath Basu, Luisa Murer, Velibor Tasic, Alexey Tsygin, Stéphane Decramer, Helena Gil-Peña, Linda Koster-Kamphuis, Claudio La Scola, Jutta Gellermann, Martin Konrad, Marc Lilien, Telma Francisco, Despoina Tramma, Peter Trnka, Selçuk Yüksel, Maria Rosa Caruso, Milan Chromek, Zelal Ekinci, Giovanni Gambaro, Jameela A Kari, Jens König, Francesca Taroni, Julia Thumfart, Francesco Trepiccione, Louise Winding, Elke Wühl, Ayşe Ağbaş, Anna Belkevich, Rosa Vargas-Poussou, Anne Blanchard, Giovanni Conti, Olivia Boyer, Ismail Dursun, Ayşe Seda Pınarbaşı, Engin Melek, Marius Miglinas, Robert Novo, Andrew Mallett, Danko Milosevic, Maria Szczepanska, Sarah Wente, Hae Il Cheong, Rajiv Sinha, Zoran Gucev, Stephanie Dufek, Daniela Iancu, Robert Kleta, Franz Schaefer, Detlef Bockenhauer
BACKGROUND: Primary distal renal tubular acidosis (dRTA) is a rare disorder, and we aimed to gather data on treatment and long-term outcome. METHODS: We contacted paediatric and adult nephrologists through European professional organizations. Responding clinicians entered demographic, biochemical, genetic and clinical data in an online form. RESULTS: Adequate data were collected on 340 patients (29 countries, female 52%). Mutation testing had been performed on 206 patients (61%); pathogenic mutations were identified in 170 patients (83%)...
February 18, 2019: Nephrology, Dialysis, Transplantation
Manaswita Jain, Rainer W J Kaiser, Katrin Bohl, Martin Hoehne, Heike Göbel, Malte P Bartram, Sandra Habbig, Roman-Ulrich Müller, Agnes B Fogo, Thomas Benzing, Bernhard Schermer, Katja Höpker, Gisela G Slaats
Recent human genetic studies have suggested an intriguing link between ciliary signaling defects and altered DNA damage responses in nephronophthisis (NPH) and related ciliopathies. However, the molecular mechanism and the role of altered DNA damage response in kidney degeneration and fibrosis have remained elusive. We recently identified the kinase-regulated DNA damage response target Apoptosis Antagonizing Transcription Factor (AATF) as a master regulator of the p53 response. Here, we characterized the phenotype of mice with genetic deletion of Aatf in tubular epithelial cells...
February 12, 2019: Kidney International
Yue Zhao, Cong Wang, Xue Hong, Jinhua Miao, Yulin Liao, Fan Fan Hou, Lili Zhou, Youhua Liu
In type 2 cardiorenal syndrome, chronic heart failure is thought to cause or promote chronic kidney disease; however, the underlying mechanisms remain poorly understood. We investigated the role of Wnt signaling in heart and kidney injury in a mouse model of cardiac hypertrophy and heart failure induced by transverse aortic constriction (TAC). At 8 weeks after TAC, cardiac hypertrophy, inflammation, and fibrosis were prominent, and echocardiography confirmed impaired cardiac function. The cardiac lesions were accompanied by upregulation of multiple Wnt ligands and activation of β-catenin, as well as activation of the renin-angiotensin system (RAS)...
February 8, 2019: Kidney International
Xinrui Li, Jing Liu, Liang Ma, Ping Fu
Chronic kidney disease (CKD) has become a global public health issue and uric acid (UA) remains a major risk factor of CKD. As the main organ for the elimination of UA, kidney owned a group of urate transporters in tubular epithelium. Kidney disease hampered the UA excretion, and the accumulation of serum UA in return harmed the renal function. Commercially, there are three kinds of agents targeting at urate-lowering, xanthine oxidoreductase inhibitor which prevents the production of UA, uricosuric which increases the concentration of UA in urine thus decreasing serum UA level, and uricase which converts UA to allantoin resulting in the dramatic decrement of serum UA...
January 23, 2019: European Journal of Medicinal Chemistry
Yoojin M Kim, David J Polzin, Aaron Rendahl, Jennifer L Granick
BACKGROUND: Active kidney injury may play a role in chronic kidney disease (CKD) progression in dogs. Neutrophil gelatinase-associated lipocalin (NGAL), a novel tubular kidney injury biomarker, may help differentiate progressive CKD from stable CKD in dogs. OBJECTIVES: To determine if urinary NGAL : creatinine ratio (UNCR) differentiates stable and progressive CKD in dogs. We hypothesized that UNCR would be higher in dogs with progressive CKD versus stable CKD...
February 14, 2019: Journal of Veterinary Internal Medicine
Aurélia Bertholet-Thomas, Nathalie Tram, Laurence Dubourg, Sandrine Lemoine, Arnaud Molin, Justine Bacchetta
Mutations in the SLC34A3 gene, encoding the sodium/phosphate cotransporter 2C (NPTIIc), induce decreased renal phosphate reabsorption, hypophosphatemia, decreased fibroblast growth factor 23 and parathyroid hormone, and increased 1,25-dihydroxyvitamin D (1,25[OH]2 D) levels. The complete phenotype is characterized by hypophosphatemia, hypercalciuria, and nephrolithiasis/nephrocalcinosis, leading to chronic kidney disease and osteoporosis in adults. We report a 15-year-old boy referred for nephrocalcinosis. The patient demonstrated hypercalcemia, hypercalciuria, normal serum phosphate level, normal tubular phosphate reabsorption, and increased serum 1,25(OH)2 D level with suppressed serum parathyroid hormone...
February 11, 2019: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Ivonne Loeffler
Interstitial fibrosis is a typical feature of end-stage renal diseases, regardless of the initial cause of kidney injury. Epithelial-to-mesenchymal transition (EMT) is a mechanism that is thought to play a role in generating the interstitial matrix-producing myofibroblasts and is prominently induced by the transforming growth factor-β 1 (TGF-β1). TGF-β1 signals through a variety of Smad and non-Smad signaling pathways, including the mitogen-activated protein kinase (MAPK) pathways. In a study published in a recent issue of Clinical Science (Clin...
February 14, 2019: Clinical Science (1979-)
Gianluca Vergine, Elisa Ravaioli, Viviana Palazzo, Giovanni Gambaro, Sabrina Giglio
We describe the case of a 5-year-old who came to our attention for a growth delay. Among the investigations planned because of the child's short stature, we performed an abdominal ultrasound showing normal-sized kidneys with signs of cortico-medullar de-differentiation, diffuse medullary hyperechogenicity with reduction of cortical thickness and cortical-medullary cysts. The ultrasound findings, also confirmed in MRI, led us to suspect a genetically determined cystic nephropathy of the nephronophthisis or medullary cystic disease type...
February 2019: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Ankur Sinha, Phone Oo, Muhammad U Asghar, Hira A Cheema, Sanwal S Mehta, Joshua C Leinwand, Kalyana Janga
Topiramate (TMP) is a broad-spectrum anticonvulsant drug used to treat a wide variety of seizure disorders, for migraine prophylaxis, and for many other indications. An important side effect of TMP is metabolic acidosis, which is mediated by renal tubular defects. TMP inhibits carbonic anhydrase, an enzyme that is necessary for acid handling in the proximal renal tubule. Patients can present with asymptomatic serum electrolyte derangements, acute change in mental status, hyperventilation, cardiac arrhythmias, or other sequelae of metabolic acidosis and associated respiratory compensation...
November 26, 2018: Curēus
S C Toma, B S Ungureanu, S Patrascu, V Surlin, I Georgescu
Colorectal cancer (CRC) is one of the most widespread malignancy, posing as a great challenge due to its high incidence and mortality in both genders. Yet, it also stands as one of the most preventable diseases because of its known malignant transformation mostly from tubular adenomas or serrated polyps, therefore offering a strong incentive to the screening programs that are being developed for this disease. Current diagnosis of CRC has surely evolved along with the evolutionary step in gastrointestinal technology of flexible endoscopy...
April 2018: Current Health Sciences Journal
Hassan Izzedine, Alexis Mathian, Stephane Champiat, Cécile Picard, Christine Mateus, Emilie Routier, Andrea Varga, David Malka, Alexandra Leary, Judith Michels, Jean-Marie Michot, Aurélien Marabelle, Olivier Lambotte, Zahir Amoura, Jean-Charles Soria, Sihem Kaaki, Nathalie Quellard, Jean-Michel Goujon, Isabelle Brocheriou
Objective: Expanded clinical experience with patients treated by pembrolizumab has accumulated. However, renal toxicities associated with this anti-programmed cell death 1 agent are poorly described because kidney histology is rarely sought. As a nephrology referral centre, we aimed to describe the clinic-biological and histopathological characteristics of pembrolizumab-related nephropathy and its response to treatment. Methods: We conducted a monocentric large case series study, including all pembrolizumab-treated cancer patients presenting a renal toxicity addressed to our centre from 2015 to 2017...
February 2019: Clinical Kidney Journal
William R Zhang, Chirag R Parikh
The current unidimensional paradigm of kidney disease detection is incompatible with the complexity and heterogeneity of renal pathology. The diagnosis of kidney disease has largely focused on glomerular filtration, while assessment of kidney tubular health has notably been absent. Following insult, the kidney tubular cells undergo a cascade of cellular responses that result in the production and accumulation of low-molecular-weight proteins in the urine and systemic circulation. Modern advancements in molecular analysis and proteomics have allowed the identification and quantification of these proteins as biomarkers for assessing and characterizing kidney diseases...
February 10, 2019: Annual Review of Physiology
Krithika Hariharan, Petra Reinke, Andreas Kurtz
Human pluripotent stem cells (hPSCs) have been well known for their ability to generate kidney cell types. We developed a protocol that utilizes a set of growth factors to give rise to kidney progenitors, which when differentiated further in a monolayer gives rise to podocyte precursors, mesangial cells, proximal and distal tubular epithelial cells, and collecting duct cells. This article describes in detail how to obtain each of these segment-specific kidney cell types from hPSCs. Once obtained as a homogenous population, these cells are invaluable for nephrotoxicity testing, for disease modeling, and in tissue engineering approaches such as 3D bioprinting and seeding on acellular matrices and scaffolds...
2019: Methods in Molecular Biology
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