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Journal of the American Society of Nephrology: JASN

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https://www.readbyqxmd.com/read/28220032/pharmacologic-blockade-of-%C3%AE-v%C3%AE-1-integrin-ameliorates-renal-failure-and-fibrosis-in-vivo
#1
Yongen Chang, Wei Ling Lau, Hyunil Jo, Kazuyuki Tsujino, Leslie Gewin, Nilgun Isik Reed, Amha Atakilit, Ane Claudia Fernandes Nunes, William F DeGrado, Dean Sheppard
Activated fibroblasts are deemed the main executors of organ fibrosis. However, regulation of the pathologic functions of these cells in vivo is poorly understood. PDGF receptor β (PDGFRβ) is highly expressed in activated pericytes, a main source of fibroblasts. Studies using a PDGFRβ promoter-driven Cre system to delete αv integrins in activated fibroblasts identified these integrins as core regulators of fibroblast activity across solid organs, including the kidneys. Here, we used the same PDGFRβ-Cre line to isolate and study renal fibroblasts ex vivo We found that renal fibroblasts express three αv integrins, namely αvβ1, αvβ3, and αvβ5...
February 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28220031/trends-in-discharge-claims-for-acute-myocardial-infarction-among-patients-on-dialysis
#2
Gautam R Shroff, Shuling Li, Charles A Herzog
Analysis of a contemporary cohort of patients on dialysis revealed that mortality from acute myocardial infarction (AMI) has decreased, whereas the prevalence of AMI has increased markedly, particularly among patients with non-ST elevation myocardial infarction (NSTEMI). Using inpatient discharge diagnosis codes (1993-2008), we determined that proportions of AMI claims decreased in the primary position (from 65% to 52%) but increased in the secondary position (from 35% to 48%). Proportions of NSTEMI codes increased remarkably in both the primary and secondary positions...
February 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28220030/novel-paradigms-of-salt-and-hypertension
#3
Wenguang Feng, Louis J Dell'Italia, Paul W Sanders
Salt resistance/sensitivity refers specifically to the effect of dietary sodium chloride (salt) intake on BP. Increased dietary salt intake promotes an early and uniform expansion of extracellular fluid volume and increased cardiac output. To compensate for these hemodynamic changes and maintain constant BP in salt resistance, renal and peripheral vascular resistance falls and is associated with an increase in production of nitric oxide. In contrast, the decline in peripheral vascular resistance and the increase in nitric oxide are impaired or absent in salt sensitivity, promoting an increase in BP in these individuals...
February 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28220029/a-novel-inhibitor-of-homeodomain-interacting-protein-kinase-2-mitigates-kidney-fibrosis-through-inhibition-of-the-tgf-%C3%AE-1-smad3-pathway
#4
Ruijie Liu, Bhaskar Das, Wenzhen Xiao, Zhengzhe Li, Huilin Li, Kyung Lee, John Cijiang He
Homeodomain interacting protein kinase 2 (HIPK2) is a critical regulator of multiple profibrotic pathways, including that of TGF-β1/Smad3. Genetic ablation of HIPK2 was shown previously to significantly reduce renal fibrosis in the experimental unilateral ureteral obstruction model and Tg26 mice, a model of HIV-associated nephropathy. To develop specific pharmacologic inhibitors of HIPK2 for antifibrotic therapy, we designed and synthesized small molecule inhibitor compounds on the basis of the predicted structure of HIPK2...
February 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28220028/perspective-on-clinical-application-of-biomarkers-in-aki
#5
Chirag R Parikh, Sherry G Mansour
Several biomarkers of renal injury have been identified but the utility of these biomarkers is largely confined to research studies, whereas widespread clinical applicability is limited. This is partly because the use of serum creatinine as the comparator has several limitations and restricts the full interpretation of biomarker performance. To highlight the potential for clinical application of biomarkers, the most pertinent biomarker data are summarized here, using clinically relevant scenarios in which biomarkers could assist with diagnostic and management dilemmas...
February 20, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28209809/macrophage-to-myofibroblast-transition-contributes-to-interstitial-fibrosis-in-chronic-renal-allograft-injury
#6
Ying-Ying Wang, Hong Jiang, Jun Pan, Xiao-Ru Huang, Yu-Cheng Wang, Hong-Feng Huang, Ka-Fai To, David J Nikolic-Paterson, Hui-Yao Lan, Jiang-Hua Chen
Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (α-smooth muscle actin [α-SMA]) markers...
February 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28209808/galactosylation-of-iga1-is-associated-with-common-variation-in-c1galt1
#7
Daniel P Gale, Karen Molyneux, David Wimbury, Patricia Higgins, Adam P Levine, Ben Caplin, Anna Ferlin, Peiran Yin, Christopher P Nelson, Horia Stanescu, Nilesh J Samani, Robert Kleta, Xueqing Yu, Jonathan Barratt
IgA nephropathy (IgAN), an important cause of kidney failure, is characterized by glomerular IgA deposition and is associated with changes in O-glycosylation of the IgA1 molecule. Here, we sought to identify genetic factors contributing to levels of galactose-deficient IgA1 (Gd-IgA1) in white and Chinese populations. Gd-IgA1 levels were elevated in IgAN patients compared with ethnically matched healthy subjects and correlated with evidence of disease progression. White patients with IgAN exhibited significantly higher Gd-IgA1 levels than did Chinese patients...
February 16, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28202497/deficiency-of-the-angiotensinase-aminopeptidase-a-increases-susceptibility-to-glomerular-injury
#8
Juan Carlos Q Velez, Ehtesham Arif, Jessalyn Rodgers, Megan P Hicks, John M Arthur, Deepak Nihalani, Evelyn T Bruner, Milos N Budisavljevic, Carl Atkinson, Wayne R Fitzgibbon, Michael G Janech
Aminopeptidase A (APA) is expressed in glomerular podocytes and tubular epithelia and metabolizes angiotensin II (AngII), a peptide known to promote glomerulosclerosis. In this study, we tested whether APA expression changes in response to progressive nephron loss or whether APA exerts a protective role against glomerular damage and during AngII-mediated hypertensive kidney injury. At advanced stages of FSGS, fawn-hooded hypertensive rat kidneys exhibited distinctly increased APA staining in areas of intact glomerular capillary loops...
February 15, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28196842/identifying-the-intracellular-function-of-apol1
#9
EDITORIAL
Leslie A Bruggeman, John F O'Toole, John R Sedor
No abstract text is available yet for this article.
February 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28193826/the-nlrp3-inflammasome-has-a-critical-role-in-peritoneal-dialysis-related-peritonitis
#10
Nicolas Hautem, Johann Morelle, Amadou Sow, Cyril Corbet, Olivier Feron, Eric Goffin, François Huaux, Olivier Devuyst
Bacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). During peritonitis, the peritoneal membrane undergoes structural and functional alterations that are mediated by IL-1β The NLRP3 inflammasome is a caspase-1-activating multiprotein complex that links sensing of microbial and stress products to activation of proinflammatory cytokines, including IL-1β The potential roles of the NLRP3 inflammasome and IL-1β in the peritoneal membrane during acute peritonitis have not been investigated...
February 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28183725/changes-in-cardiac-output-and-perfusion-during-hemodialysis-and-hemodiafiltration-treatments-determined-by-cardiac-magnetic-resonance-imaging
#11
EDITORIAL
Peter J Blankestijn, Andrew Davenport
No abstract text is available yet for this article.
February 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28179433/il-36-signaling-facilitates-activation-of-the-nlrp3-inflammasome-and-il-23-il-17-axis-in-renal-inflammation-and-fibrosis
#12
Hsi-Hua Chi, Kuo-Feng Hua, Yu-Chuan Lin, Ching-Liang Chu, Chih-Yu Hsieh, Yu-Juei Hsu, Shuk-Man Ka, Yu-Ling Tsai, Feng-Cheng Liu, Ann Chen
IL-36 cytokines are proinflammatory and have an important role in innate and adaptive immunity, but the role of IL-36 signaling in renal tubulointerstitial lesions (TILs), a major prognostic feature of renal inflammation and fibrosis, remains undetermined. In this study, increased IL-36α expression detected in renal biopsy specimens and urine samples from patients with renal TILs correlated with renal function impairment. We confirmed the increased expression of IL-36α in the renal tubular epithelial cells of a mouse model of unilateral ureteral obstruction (UUO) and related cell models using mechanically induced pressure, oxidative stress, or high mobility group box 1...
February 8, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28174217/diagnosis-and-treatment-of-hyponatremia-compilation-of-the-guidelines
#13
Ewout J Hoorn, Robert Zietse
Hyponatremia is a common water balance disorder that often poses a diagnostic or therapeutic challenge. Therefore, guidelines were developed by professional organizations, one from within the United States (2013) and one from within Europe (2014). This review discusses the diagnosis and treatment of hyponatremia, comparing the two guidelines and highlighting recent developments. Diagnostically, the initial step is to differentiate hypotonic from nonhypotonic hyponatremia. Hypotonic hyponatremia is further differentiated on the basis of urine osmolality, urine sodium level, and volume status...
February 7, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28159782/effect-of-tenapanor-on-serum-phosphate-in-patients-receiving-hemodialysis
#14
Geoffrey A Block, David P Rosenbaum, Maria Leonsson-Zachrisson, Magnus Åstrand, Susanne Johansson, Mikael Knutsson, Anna Maria Langkilde, Glenn M Chertow
Hyperphosphatemia is common among patients with CKD stage 5D and is associated with morbidity and mortality. Current guidelines recommend lowering serum phosphate concentrations toward normal. Tenapanor is a minimally absorbed small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 that functions in the gut to reduce sodium and phosphate absorption. This randomized, double-blind, placebo-controlled trial assessed the effects of tenapanor on serum phosphate concentration in patients with hyperphosphatemia receiving hemodialysis...
February 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28159781/insights-into-diabetic-kidney-disease-using-urinary-proteomics-and-bioinformatics
#15
Julie A D Van, James W Scholey, Ana Konvalinka
A number of proteomic and peptidomic analyses of urine from diabetic subjects have been published in the quest for a biomarker that predicts progression of nephropathy. Less attention has been paid to the relationships between urinary proteins and the underlying biological processes revealed by the analyses. In this review, we focus on the biological processes identified by studying urinary proteins and protein-protein interactions at each stage of diabetic nephropathy to provide an overview of the events underlying progression of kidney disease reflected in the urine...
February 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28159780/growth-differentiation-factor-15-and-risk-of-ckd-progression
#16
Viji Nair, Cassianne Robinson-Cohen, Michelle R Smith, Keith A Bellovich, Zeenat Yousuf Bhat, Maria Bobadilla, Frank Brosius, Ian H de Boer, Laurent Essioux, Ivan Formentini, Crystal A Gadegbeku, Debbie Gipson, Jennifer Hawkins, Jonathan Himmelfarb, Bryan Kestenbaum, Matthias Kretzler, Maria Chiara Magnone, Kalyani Perumal, Susan Steigerwalt, Wenjun Ju, Nisha Bansal
Growth differentiation factor-15 (GDF-15) is a member of the TGF-β cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of GDF15 mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function...
February 3, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28154201/quantitative-three-dimensional-tissue-cytometry-to-study-kidney-tissue-and-resident-immune-cells
#17
Seth Winfree, Shehnaz Khan, Radmila Micanovic, Michael T Eadon, Katherine J Kelly, Timothy A Sutton, Carrie L Phillips, Kenneth W Dunn, Tarek M El-Achkar
Analysis of the immune system in the kidney relies predominantly on flow cytometry. Although powerful, the process of tissue homogenization necessary for flow cytometry analysis introduces bias and results in the loss of morphologic landmarks needed to determine the spatial distribution of immune cells. An ideal approach would support three-dimensional (3D) tissue cytometry: an automated quantitation of immune cells and associated spatial parameters in 3D image volumes collected from intact kidney tissue. However, widespread application of this approach is limited by the lack of accessible software tools for digital analysis of large 3D microscopy data...
February 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28154200/pals1-haploinsufficiency-results-in-proteinuria-and-cyst-formation
#18
Thomas Weide, Beate Vollenbröker, Ulf Schulze, Ivona Djuric, Maria Edeling, Jakob Bonse, Florian Hochapfel, Olga Panichkina, Dirk-Oliver Wennmann, Britta George, Seonhee Kim, Christoph Daniel, Jochen Seggewiß, Kerstin Amann, Wilhelm Kriz, Michael P Krahn, Hermann Pavenstädt
The nephron is the basic physiologic subunit of the mammalian kidney and is made up of several apicobasally polarized epithelial cell types. The process of apicobasal polarization in animal cells is controlled by the evolutionarily conserved Crumbs (CRB), Partitioning-defective, and Scribble protein complexes. Here, we investigated the role of protein associated with LIN-7 1 (Pals1, also known as Mpp5), a core component of the apical membrane-determining CRB complex in the nephron. Pals1 interacting proteins, including Crb3 and Wwtr1/Taz, have been linked to renal cyst formation in mice before...
February 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28154199/skin-sodium-concentration-correlates-with-left-ventricular-hypertrophy-in-ckd
#19
Markus P Schneider, Ulrike Raff, Christoph Kopp, Johannes B Scheppach, Sebastian Toncar, Christoph Wanner, Georg Schlieper, Turgay Saritas, Jürgen Floege, Matthias Schmid, Anna Birukov, Anke Dahlmann, Peter Linz, Rolf Janka, Michael Uder, Roland E Schmieder, Jens M Titze, Kai-Uwe Eckardt
The pathogenesis of left ventricular hypertrophy in patients with CKD is incompletely understood. Sodium intake, which is usually assessed by measuring urinary sodium excretion, has been inconsistently linked with left ventricular hypertrophy. However, tissues such as skin and muscle may store sodium. Using (23)sodium-magnetic resonance imaging, a technique recently developed for the assessment of tissue sodium content in humans, we determined skin sodium content at the level of the calf in 99 patients with mild to moderate CKD (42 women; median [range] age, 65 [23-78] years)...
February 2, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28154198/il-33-mediated-expansion-of-type-2-innate-lymphoid-cells-protects-from-progressive-glomerulosclerosis
#20
Jan-Hendrik Riedel, Martina Becker, Kerstin Kopp, Mathis Düster, Silke R Brix, Catherine Meyer-Schwesinger, Luis A Kluth, Ann-Christin Gnirck, Madena Attar, Sonja Krohn, Boris Fehse, Rolf A K Stahl, Ulf Panzer, Jan-Eric Turner
Innate lymphoid cells (ILCs) have an important role in the immune system's response to different forms of infectious and noninfectious pathologies. In particular, IL-5- and IL-13-producing type 2 ILCs (ILC2s) have been implicated in repair mechanisms that restore tissue integrity after injury. However, the presence of renal ILCs in humans has not been reported. In this study, we show that ILC populations are present in the healthy human kidney. A detailed characterization of kidney-residing ILC populations revealed that IL-33 receptor-positive ILC2s are a major ILC subtype in the kidney of humans and mice...
February 2, 2017: Journal of the American Society of Nephrology: JASN
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