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Kidney International

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https://www.readbyqxmd.com/read/28807612/the-role-of-trimethylamine-n-oxide-as-a-mediator-of-cardiovascular-complications-in-chronic-kidney-disease
#1
James A P Tomlinson, David C Wheeler
Patients with chronic kidney disease (CKD) have an enhanced risk of cardiovascular (CV) morbidity and mortality when compared with age- and gender-matched individuals with normal kidney function. Trimethlyamine N-oxide (TMAO) is a gut-derived amine oxide that has been implicated in the causation of CV diseases. Plasma TMAO is cleared by the kidney, and TMAO levels are elevated in CKD. Experimental studies have identified pathogenic mechanisms by which TMAO may contribute to CV disease through dysregulation of lipid metabolism, enhanced macrophage foam cell formation, and platelet dysfunction...
August 11, 2017: Kidney International
https://www.readbyqxmd.com/read/28797473/biomarker-research-to-improve-clinical-outcomes-of-peritoneal-dialysis-consensus-of-the-european-training-and-research-in-peritoneal-dialysis-eutripd-network
#2
REVIEW
Christoph Aufricht, Robert Beelen, Matthias Eberl, Michel Fischbach, Donald Fraser, Achim Jörres, Klaus Kratochwill, Manuel LópezCabrera, Peter Rutherford, Claus-Peter Schmitt, Nicholas Topley, Janusz Witowski
Peritoneal dialysis (PD) therapy substantially requires biomarkers as tools to identify patients who are at the highest risk for PD-related complications and to guide personalized interventions that may improve clinical outcome in the individual patient. In this consensus article, members of the European Training and Research in Peritoneal Dialysis Network (EuTRiPD) review the current status of biomarker research in PD and suggest a selection of biomarkers that can be relevant to the care of PD patients and that are directly accessible in PD effluents...
August 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28760336/dietary-magnesium-supplementation-prevents-and-reverses-vascular-and-soft-tissue-calcifications-in-uremic-rats
#3
Juan M Diaz-Tocados, Alan Peralta-Ramirez, María E Rodríguez-Ortiz, Ana I Raya, Ignacio Lopez, Carmen Pineda, Carmen Herencia, Addy Montes de Oca, Noemi Vergara, Sonja Steppan, M Victoria Pendon-Ruiz de Mier, Paula Buendía, Andrés Carmona, Julia Carracedo, Juan F Alcalá-Díaz, Joao Frazao, Julio M Martínez-Moreno, Antonio Canalejo, Arnold Felsenfeld, Mariano Rodriguez, Escolástico Aguilera-Tejero, Yolanda Almadén, Juan R Muñoz-Castañeda
Although magnesium has been shown to prevent vascular calcification in vitro, controlled in vivo studies in uremic animal models are limited. To determine whether dietary magnesium supplementation protects against the development of vascular calcification, 5/6 nephrectomized Wistar rats were fed diets with different magnesium content increasing from 0.1 to 1.1%. In one study we analyzed bone specimens from rats fed 0.1%, 0.3%, and 0.6% magnesium diets, and in another study we evaluated the effect of intraperitoneal magnesium on vascular calcification in 5/6 nephrectomized rats...
July 28, 2017: Kidney International
https://www.readbyqxmd.com/read/28760335/microrna-21-regulates-peroxisome-proliferator-activated-receptor-alpha-a-molecular-mechanism-of-cardiac-pathology-in-cardiorenal-syndrome-type-4
#4
Sandra Chuppa, Mingyu Liang, Pengyuan Liu, Yong Liu, Marc C Casati, Allen W Cowley, Leah Patullo, Alison J Kriegel
Cardiovascular events are the leading cause of death in patients with chronic kidney disease (CKD), although the pathological mechanisms are poorly understood. Here we longitudinally characterized left ventricle pathology in a 5/6 nephrectomy rat model of CKD and identify novel molecular mediators. Next-generation sequencing of left ventricle mRNA and microRNA (miRNA) was performed at physiologically distinct points in disease progression, identifying alterations in genes in numerous immune, lipid metabolism, and inflammatory pathways, as well as several miRNAs...
July 28, 2017: Kidney International
https://www.readbyqxmd.com/read/28756872/retinoic-acid-improves-nephrotoxic-serum-induced-glomerulonephritis-through-activation-of-podocyte-retinoic-acid-receptor-%C3%AE
#5
Yan Dai, Anqun Chen, Ruijie Liu, Leyi Gu, Shuchita Sharma, Weijing Cai, Fadi Salem, David J Salant, Jeffrey W Pippin, Stuart J Shankland, Marcus J Moeller, Norbert B Ghyselinck, Xiaquiang Ding, Peter Y Chuang, Kyung Lee, John Cijiang He
Proliferation of glomerular epithelial cells, including podocytes, is a key histologic feature of crescentic glomerulonephritis. We previously found that retinoic acid (RA) inhibits proliferation and induces differentiation of podocytes by activating RA receptor-α (RARα) in a murine model of HIV-associated nephropathy. Here, we examined whether RA would similarly protect podocytes against nephrotoxic serum-induced crescentic glomerulonephritis and whether this effect was mediated by podocyte RARα. RA treatment markedly improved renal function and reduced the number of crescentic lesions in nephritic wild-type mice, while this protection was largely lost in mice with podocyte-specific ablation of Rara (Pod-Rara knockout)...
July 27, 2017: Kidney International
https://www.readbyqxmd.com/read/28754558/magnetic-resonance-t2-mapping-and-diffusion-weighted-imaging-for-early-detection-of-cystogenesis-and-response-to-therapy-in-a-mouse-model-of-polycystic-kidney-disease
#6
Mareike Franke, Bettina Baeßler, Jan Vechtel, Claudia Dafinger, Martin Höhne, Lori Borgal, Heike Göbel, Friederike Koerber, David Maintz, Thomas Benzing, Bernhard Schermer, Thorsten Persigehl
Polycystic kidney disease (PKD) is among the leading causes of end-stage renal disease. Increasing evidence exists that molecular therapeutic strategies targeted to cyst formation and growth might be more efficacious in early disease stages, highlighting the growing need for sensitive biomarkers. Here we apply quantitative magnetic resonance imaging techniques of T2 mapping and diffusion-weighted imaging in the jck mouse model for PKD using a clinical 3.0 T scanner. We tested whether kidney T2 values and the apparent diffusion coefficient (ADC) are superior to anatomical imaging parameters in the detection of early cystogenesis, as shown on macro- and histopathology...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28754557/accelerated-podocyte-detachment-and-progressive%C3%A2-podocyte-loss-from-glomeruli-with%C3%A2-age%C3%A2-in-alport-syndrome
#7
Fangrui Ding, Larysa Wickman, Su Q Wang, Yanqin Zhang, Fang Wang, Farsad Afshinnia, Jeffrey Hodgin, Jie Ding, Roger C Wiggins
Podocyte depletion is a common mechanism driving progression in glomerular diseases. Alport Syndrome glomerulopathy, caused by defective α3α4α5 (IV) collagen heterotrimer production by podocytes, is associated with an increased rate of podocyte detachment detectable in urine and reduced glomerular podocyte number suggesting that defective podocyte adherence to the glomerular basement membrane might play a role in driving progression. Here a genetically phenotyped Alport Syndrome cohort of 95 individuals [urine study] and 41 archived biopsies [biopsy study] were used to test this hypothesis...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28754556/kidney-function-is-associated-with-an-altered-protein-composition-of-high-density-lipoprotein
#8
Katya B Rubinow, Clark M Henderson, Cassianne Robinson-Cohen, Jonathan Himmelfarb, Ian H de Boer, Tomas Vaisar, Bryan Kestenbaum, Andrew N Hoofnagle
Patients with chronic kidney disease (CKD) exhibit a myriad of metabolic derangements, including dyslipidemia characterized by low plasma concentrations of high-density lipoprotein (HDL)-associated cholesterol. However, the effects of kidney disease on HDL composition have not been comprehensively determined. Here we used a targeted mass spectrometric approach to quantify 38 proteins contained in the HDL particles within a CKD cohort of 509 participants with a broad range of estimated glomerular filtration rates (eGFRs) (CKD stages I-V, and a mean eGFR of 45...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28754555/elastin-insufficiency-causes-hypertension-structural%C3%A2-defects-and-abnormal-remodeling-of%C3%A2-renal-vascular-signaling
#9
Elizabeth A Owens, Li Jie, Beverly A S Reyes, Elisabeth J Van Bockstaele, Patrick Osei-Owusu
Elastin deficiency causes vascular stiffening, a leading risk for hypertension and chronic kidney disease (CKD). The mechanisms mediating hypertension and/or CKD pathogenesis due to elastin deficiency are poorly understood. Using the elastin heterozygous (Eln+/-) mouse model, we tested whether renal dysfunction due to elastin deficiency occurs independently of and precedes the development of hypertension. We assessed blood pressure and renal hemodynamics in 30-day and 12-week-old male and female mice. At P30, blood pressure of Eln+/- mice was similar to wild-type controls; however, renal blood flow was lower, whereas renal vascular resistance was augmented at baseline in Eln+/- mice...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28754554/impairment-of-the-carnitine-organic-cation-transporter-1-ergothioneine-axis-is-mediated-by-intestinal-transporter-dysfunction-in-chronic-kidney-disease
#10
Yasuyuki Shinozaki, Kengo Furuichi, Tadashi Toyama, Shinji Kitajima, Akinori Hara, Yasunori Iwata, Norihiko Sakai, Miho Shimizu, Shuichi Kaneko, Noriyoshi Isozumi, Shushi Nagamori, Yoshikatsu Kanai, Tomoko Sugiura, Yukio Kato, Takashi Wada
Carnitine/organic cation transporter 1 (OCTN1) is a specific transporter of the food-derived antioxidant ergothioneine. Ergothioneine is absorbed by intestinal OCTN1, distributed through the bloodstream, and incorporated into each organ by OCTN1. OCTN1 expression is upregulated in injured tissues, and promotes ergothioneine uptake to reduce further damage caused by oxidative stress. However, the role of the OCTN1-ergothioneine axis in kidney-intestine cross-talk and chronic kidney disease (CKD) progression remains unclear...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28754553/real-time-in%C3%A2-vivo-mitochondrial-redox-assessment-confirms-enhanced-mitochondrial-reactive-oxygen-species-in-diabetic-nephropathy
#11
Daniel L Galvan, Shawn S Badal, Jianyin Long, Benny H Chang, Paul T Schumacker, Paul A Overbeek, Farhad R Danesh
While increased mitochondrial reactive oxygen species have been commonly implicated in a variety of disease states, their in vivo role in the pathogenesis of diabetic nephropathy remains controversial. Using a two-photon imaging approach with a genetically encoded redox biosensor, we monitored mitochondrial redox state in the kidneys of experimental models of diabetes in real-time in vivo. Diabetic (db/db) mice that express a redox-sensitive Green Fluorescent Protein biosensor (roGFP) specifically in the mitochondrial matrix (db/dbmt-roGFP) were generated, allowing dynamic monitoring of redox changes in the kidneys...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28754552/ubiquitin-c-terminal-hydrolase-l1-is-required-for%C3%A2-regulated-protein-degradation-through-the%C3%A2-ubiquitin-proteasome-system-in-kidney
#12
Victoria Radón, Maire Czesla, Julia Reichelt, Julia Fehlert, Anna Hammel, Alva Rosendahl, Jan-Hendrik Knop, Thorsten Wiech, Ulrich O Wenzel, Marlies Sachs, Anna T Reinicke, Rolf A K Stahl, Catherine Meyer-Schwesinger
Ubiquitin C-terminal hydrolase L1 (UCH-L1) is a major deubiquitinating enzyme of the nervous system and associated with the development of neurodegenerative diseases. We have previously shown that UCH-L1 is found in tubular and parietal cells of the kidney and is expressed de novo in injured podocytes. Since the role of UCH-L1 in the kidney is unknown we generated mice with a constitutive UCH-L1-deficiency to determine its role in renal health and disease. UCH-L1-deficient mice developed proteinuria, without gross changes in glomerular morphology...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28754551/the-fragility-of-significant-results-underscores-the-need-of-larger-randomized-controlled-trials-in-nephrology
#13
Lani R Shochet, Peter G Kerr, Kevan R Polkinghorne
The Fragility Index is a tool for testing robustness of randomized controlled trial results for dichotomous outcomes. It describes the minimum number of individuals in whom changing an event status would render a statistically significant result nonsignificant. Here we identified all randomized controlled trials in five nephrology and five general journals from 2005-2014. A total of 127 randomized controlled trials reporting at least one dichotomous statistically significant outcome (p less than 0.05) were included and the Fragility Index was calculated...
July 26, 2017: Kidney International
https://www.readbyqxmd.com/read/28750931/factor-h-autoantibody-is-associated-with-atypical-hemolytic-uremic-syndrome-in-children-in-the-united-kingdom-and-ireland
#14
Vicky Brocklebank, Sally Johnson, Thomas P Sheerin, Stephen D Marks, Rodney D Gilbert, Kay Tyerman, Meredith Kinoshita, Atif Awan, Amrit Kaur, Nicholas Webb, Shivaram Hegde, Eric Finlay, Maggie Fitzpatrick, Patrick R Walsh, Edwin K S Wong, Caroline Booth, Larissa Kerecuk, Alan D Salama, Mike Almond, Carol Inward, Timothy H Goodship, Neil S Sheerin, Kevin J Marchbank, David Kavanagh
Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator...
July 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28750930/positive-antineutrophil-cytoplasmic-antibody-serology-in-patients-with-lupus-nephritis-is-associated-with-distinct-histopathologic-features-on%C3%A2-renal-biopsy
#15
Tabitha Turner-Stokes, Hannah R Wilson, Massimiliano Morreale, Ana Nunes, Tom Cairns, H Terence Cook, Charles D Pusey, Ruth M Tarzi, Liz Lightstone
Class IV-S lupus nephritis is often associated with more necrosis and fewer subendothelial immune deposits compared to class IV-G lupus nephritis, suggestive of necrotising glomerular inflammation found in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. ANCAs are present in a significant proportion of patients with lupus nephritis. Here we determine whether ANCAs are associated with distinct clinical and histopathologic features of lupus nephritis. Thirty-two ANCA-positive biopsies were compared to 222 ANCA-negative biopsies from patients with lupus nephritis...
July 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28750929/blood-pressure-parameters-are-associated-with-all-cause-and-cause-specific-mortality-in-chronic-kidney-disease
#16
Sankar D Navaneethan, Jesse D Schold, Stacey E Jolly, Susana Arrigain, Matthew F Blum, Wolfgang C Winkelmayer, Joseph V Nally
Previous observational studies reported J or U-shaped associations between blood pressure parameters and mortality in patients with chronic kidney disease (CKD). Here we examined the associations of different blood pressure levels with various causes of death in a CKD population that included patients with eGFR 15-59 ml/min/1.73 m(2) with underlying hypertension receiving at least one antihypertensive agent. We obtained data on date and cause of death from State Department of Health mortality files and classified deaths into three categories: cardiovascular, malignancy-related, and non-cardiovascular/non-malignancy related...
July 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28750928/paricalcitol-and-cinacalcet-have-disparate-actions-on-parathyroid-oxyphil-cell-content-in-patients-with-chronic-kidney-disease
#17
Cynthia Ritter, Brent Miller, Daniel W Coyne, Diptesh Gupta, Sijie Zheng, Alex J Brown, Eduardo Slatopolsky
The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the oxyphil cell content in patients with CKD to further investigate the genesis of these cells...
July 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28750927/fibroblast-growth-factor-1-ameliorates-diabetic-nephropathy-by-an-anti-inflammatory-mechanism
#18
Guang Liang, Lintao Song, Zilu Chen, Yuanyuan Qian, Junjun Xie, Longwei Zhao, Qian Lin, Guanghui Zhu, Yi Tan, Xiaokun Li, Moosa Mohammadi, Zhifeng Huang
Inflammation plays a central role in the etiology of diabetic nephropathy, a global health issue. We observed a significant reduction in the renal expression of fibroblast growth factor 1, a known mitogen and insulin sensitizer, in patients with diabetic nephropathy and in mouse models implying that fibroblast growth factor 1 possesses beneficial anti-inflammatory and renoprotective activities in vivo. To test this possibility, we investigated the effects of chronic i.p. administration of fibroblast growth factor 1 into both the streptozotocin-induced type 1 diabetes and db/db type 2 diabetes models...
July 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28750925/%C3%AE-1-4-galactosyltransferase-1-is-a-novel-receptor-for-iga-in-human-mesangial-cells
#19
Karen Molyneux, David Wimbury, Izabella Pawluczyk, Masahiro Muto, Jasraj Bhachu, Peter R Mertens, John Feehally, Jonathan Barratt
IgA nephropathy is characterized by mesangial deposition of IgA, mesangial cell proliferation, and extracellular matrix production. Mesangial cells bind IgA, but the identity of all potential receptors involved remains incomplete. The transferrin receptor (CD71) acts as a mesangial cell IgA receptor and its expression is upregulated in many forms of glomerulonephritis, including IgA nephropathy. CD71 is not expressed in healthy glomeruli and blocking CD71 does not completely abrogate mesangial cell IgA binding...
July 24, 2017: Kidney International
https://www.readbyqxmd.com/read/28739141/amp-activated-protein-kinase-myocardin-related-transcription-factor-a-signaling-regulates-fibroblast-activation-and-renal-fibrosis
#20
Yuguo Wang, Li Jia, Zhaoyong Hu, Mark L Entman, William E Mitch, Yanlin Wang
Chronic kidney disease is a major cause of death, and renal fibrosis is a common pathway leading to the progression of this disease. Although activated fibroblasts are responsible for the production of the extracellular matrix and the development of renal fibrosis, the molecular mechanisms underlying fibroblast activation are not fully defined. Here we examined the functional role of AMP-activated protein kinase (AMPK) in the activation of fibroblasts and the development of renal fibrosis. AMPKα1 was induced in the kidney during the development of renal fibrosis...
July 21, 2017: Kidney International
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