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Journal of the American Society of Nephrology: JASN

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https://www.readbyqxmd.com/read/30021759/a-controlled-increase-in-dietary-phosphate-elevates-bp-in-healthy-human-subjects
#1
Jaber Mohammad, Roberto Scanni, Lukas Bestmann, Henry N Hulter, Reto Krapf
Background Despite epidemiologic evidence for increased cardiovascular morbidity and mortality associated with both high dietary and serum phosphate in humans with normal renal function, no controlled phosphate intervention studies of systemic hemodynamics have been reported. Higher serum 25(OH) vitamin D levels are associated with better cardiovascular outcomes, but vitamin D increases intestinal phosphate absorption. Methods We conducted a prospective outpatient study with blinded assessment in 20 young adults with normal renal function randomized to high phosphate (regular diet plus 1 mmol/kg body wt per day of Na as neutral sodium phosphate) or low phosphate (regular diet plus lanthanum, 750 mg thrice/day, plus 0...
July 18, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30012572/erratum
#2
(no author information available yet)
No abstract text is available yet for this article.
July 16, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30012571/strong-association-of-the-hla-dr-dq-locus-with-childhood-steroid-sensitive-nephrotic-syndrome-in-the-japanese-population
#3
Xiaoyuan Jia, Tomoko Horinouchi, Yuki Hitomi, Akemi Shono, Seik-Soon Khor, Yosuke Omae, Kaname Kojima, Yosuke Kawai, Masao Nagasaki, Yoshitsugu Kaku, Takayuki Okamoto, Yoko Ohwada, Kazuhide Ohta, Yusuke Okuda, Rika Fujimaru, Ken Hatae, Naonori Kumagai, Emi Sawanobori, Hitoshi Nakazato, Yasufumi Ohtsuka, Koichi Nakanishi, Yuko Shima, Ryojiro Tanaka, Akira Ashida, Koichi Kamei, Kenji Ishikura, Kandai Nozu, Katsushi Tokunaga, Kazumoto Iijima
Background Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown. Methods We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six HLA genes ( HLA-A , -C, -B , -DRB1 , -DQB1 , and -DPB1 ) was conducted on the basis of Japanese-specific references...
July 16, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30006419/significantly-lower-rates-of-kidney-transplantation-among-candidates-listed-with-the-veterans-administration-a-national-and-local-comparison
#4
Joshua J Augustine, Susana Arrigain, Krishna Balabhadrapatruni, Niraj Desai, Jesse D Schold
BACKGROUND: The process for evaluating kidney transplant candidates and applicable centers is distinct for patients with Veterans Administration (VA) coverage. We compared transplant rates between candidates on the kidney waiting list with VA coverage and those with other primary insurance. METHODS: Using the Scientific Registry of Transplant Recipients database, we obtained data for all adult patients in the United States listed for a primary solitary kidney transplant between January 2004 and August 2016...
July 13, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30006418/authors-reply
#5
LETTER
William G Herrington, Killian Donovan, Borislava Mihaylova
No abstract text is available yet for this article.
July 13, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30006417/acute-declines-in-renal-function-during-intensive-bp-lowering-and-long-term-risk-of-death
#6
Elaine Ku, Joachim H Ix, Kenneth Jamerson, Navdeep Tangri, Feng Lin, Jennifer Gassman, Miroslaw Smogorzewski, Mark J Sarnak
BACKGROUND: During intensive BP lowering, acute declines in renal function are common, thought to be hemodynamic, and potentially reversible. We previously showed that acute declines in renal function ≥20% during intensive BP lowering were associated with higher risk of ESRD. Here, we determined whether acute declines in renal function during intensive BP lowering were associated with mortality risk among 1660 participants of the African American Study of Kidney Disease and Hypertension and the Modification of Diet in Renal Disease Trial...
July 13, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30006416/fibroblast-growth-factor-23-is-not-a-single-bystander-in-chronic-kidney-disease-mortality
#7
LETTER
Solenne Pelletier, Denis Fouque
No abstract text is available yet for this article.
July 13, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30006415/structural-basis-of-highly-specific-interaction-between-nephrin-and-magi1-in-slit-diaphragm-assembly-and-signaling
#8
Zhuangfeng Weng, Yuan Shang, Zeyang Ji, Fei Ye, Lin Lin, Rongguang Zhang, Jinwei Zhu
BACKGROUND: The slit diaphragm is a specialized adhesion junction between opposing podocytes, establishing the final filtration barrier that prevents passage of proteins from the capillary lumen into the urinary space. Nephrin, the key structural and signaling adhesion molecule expressed in the slit diaphragm, contains an evolutionally conserved, atypical PDZ-binding motif (PBM) reported to bind to a variety of proteins in the slit diaphragm. Several mutations in NPHS1 (the gene encoding nephrin) that result in nephrin lacking an intact PBM are associated with glomerular diseases...
July 13, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30002222/the-human-fsgs-causing-anln-r431c-mutation-induces-dysregulated-pi3k-akt-mtor-rac1-signaling-in-podocytes
#9
Gentzon Hall, Brandon M Lane, Kamal Khan, Igor Pediaditakis, Jianqiu Xiao, Guanghong Wu, Liming Wang, Maria E Kovalik, Megan Chryst-Stangl, Erica E Davis, Robert F Spurney, Rasheed A Gbadegesin
BACKGROUND: We previously reported that mutations in the anillin ( ANLN ) gene cause familial forms of FSGS. ANLN is an F-actin binding protein that modulates podocyte cell motility and interacts with the phosphoinositide 3-kinase (PI3K) pathway through the slit diaphragm adaptor protein CD2-associated protein (CD2AP). However, it is unclear how the ANLN mutations cause the FSGS phenotype. We hypothesized that the R431C mutation exerts its pathogenic effects by uncoupling ANLN from CD2AP...
July 12, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/30002221/single-cell-sequencing-the-glomerulus-unraveling-the-molecular-programs-of-glomerular-filtration-one-cell-at-a-time
#10
Matthias Kretzler, Rajasree Menon
No abstract text is available yet for this article.
July 12, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29991491/abcc6-deficiency-promotes-development-of-randall-plaque
#11
Emmanuel Letavernier, Gilles Kauffenstein, Léa Huguet, Nastassia Navasiolava, Elise Bouderlique, Ellie Tang, Léa Delaitre, Dominique Bazin, Marta de Frutos, Clément Gay, Joëlle Perez, Marie-Christine Verpont, Jean-Philippe Haymann, Viola Pomozi, Janna Zoll, Olivier Le Saux, Michel Daudon, Georges Leftheriotis, Ludovic Martin
BACKGROUND: Pseudoxanthoma elasticum (PXE) is a genetic disease caused by mutations in the ABCC6 gene that result in low pyrophosphate levels and subsequent progressive soft tissue calcifications. PXE mainly affects the skin, retina, and arteries. However, many patients with PXE experience kidney stones. We determined the prevalence of this pathology in patients with PXE and examined the possible underlying mechanisms in murine models. METHODS: We conducted a retrospective study in a large cohort of patients with PXE and analyzed urine samples and kidneys from Abcc6 -/- mice at various ages...
July 10, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29986871/donald-seldin-a-transformative-leader-in-medicine-and-nephrology
#12
Robert Alpern, Gerhard Giebisch
No abstract text is available yet for this article.
July 9, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29980651/mechanisms-underlying-increased-timp2-and-igfbp7-urinary-excretion-in-experimental-aki
#13
Ali C M Johnson, Richard A Zager
BACKGROUND: Recent clinical data support the utility/superiority of a new AKI biomarker ("NephroCheck"), the arithmetic product of urinary TIMP × IGFBP7 concentrations. However, the pathophysiologic basis for its utility remains ill defined. METHODS: To clarify this issue, CD-1 mice were subjected to either nephrotoxic (glycerol, maleate) or ischemic AKI. Urinary TIMP2/IGFBP7 concentrations were determined at 4 and 18 hours postinjury and compared with urinary albumin levels...
July 6, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29980650/single-cell-transcriptomics-of-a-human-kidney-allograft-biopsy-specimen-defines-a-diverse-inflammatory-response
#14
Haojia Wu, Andrew F Malone, Erinn L Donnelly, Yuhei Kirita, Kohei Uchimura, Sai M Ramakrishnan, Joseph P Gaut, Benjamin D Humphreys
Background Single-cell genomics techniques are revolutionizing our ability to characterize complex tissues. By contrast, the techniques used to analyze renal biopsy specimens have changed little over several decades. We tested the hypothesis that single-cell RNA-sequencing can comprehensively describe cell types and states in a human kidney biopsy specimen. Methods We generated 8746 single-cell transcriptomes from a healthy adult kidney and a single kidney transplant biopsy core by single-cell RNA-sequencing...
July 6, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29976587/phosphorylation-of-acetyl-coa-carboxylase-by-ampk-reduces-renal-fibrosis-and-is-essential-for-the-anti-fibrotic-effect-of-metformin
#15
Mardiana Lee, Marina Katerelos, Kurt Gleich, Sandra Galic, Bruce E Kemp, Peter F Mount, David A Power
BACKGROUND: Expression of genes regulating fatty acid metabolism is reduced in tubular epithelial cells from kidneys with tubulointerstitial fibrosis (TIF), thus decreasing the energy produced by fatty acid oxidation (FAO). Acetyl-CoA carboxylase (ACC), a target for the energy-sensing AMP-activating protein kinase (AMPK), is the major controller of the rate of FAO within cells. Metformin has a well described antifibrotic effect, and increases phosphorylation of ACC by AMPK, thereby increasing FAO...
July 5, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29976586/efficient-gene-transfer-to-kidney-mesenchymal-cells-using-a-synthetic-adeno-associated-viral-vector
#16
Yoichiro Ikeda, Zhao Sun, Xiao Ru, Luk H Vandenberghe, Benjamin D Humphreys
BACKGROUND: After injury, mesenchymal progenitors in the kidney interstitium differentiate into myofibroblasts, cells that have a critical role in kidney fibrogenesis. The ability to deliver genetic material to myofibroblast progenitors could allow new therapeutic approaches to treat kidney fibrosis. Preclinical and clinical studies show that adeno-associated viruses (AAVs) efficiently and safely transduce various tissue targets in vivo ; however, protocols for transduction of kidney mesenchymal cells have not been established...
July 5, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29967284/noninvasive-immunohistochemical-diagnosis-and-novel-muc1-mutations-causing-autosomal-dominant-tubulointerstitial-kidney-disease
#17
Martina Živná, Kendrah Kidd, Anna Přistoupilová, Veronika Barešová, Mathew DeFelice, Brendan Blumenstiel, Maegan Harden, Peter Conlon, Peter Lavin, Dervla M Connaughton, Hana Hartmannová, Kateřina Hodaňová, Viktor Stránecký, Alena Vrbacká, Petr Vyleťal, Jan Živný, Miroslav Votruba, Jana Sovová, Helena Hůlková, Victoria Robins, Rebecca Perry, Andrea Wenzel, Bodo B Beck, Tomáš Seeman, Ondřej Viklický, Sylvie Rajnochová-Bloudíčková, Gregory Papagregoriou, Constantinos C Deltas, Seth L Alper, Anna Greka, Anthony J Bleyer, Stanislav Kmoch
BACKGROUND: Autosomal dominant tubulointerstitial kidney disease caused by mucin-1 gene ( MUC1 ) mutations (ADTKD- MUC1 ) is characterized by progressive kidney failure. Genetic evaluation for ADTKD- MUC1 specifically tests for a cytosine duplication that creates a unique frameshift protein (MUC1fs). Our goal was to develop immunohistochemical methods to detect the MUC1fs created by the cytosine duplication and, possibly, by other similar frameshift mutations and to identify novel MUC1 mutations in individuals with positive immunohistochemical staining for the MUC1fs protein...
July 2, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29959198/detection-of-splicing-abnormalities-and-genotype-phenotype-correlation-in-x-linked-alport-syndrome
#18
Tomoko Horinouchi, Kandai Nozu, Tomohiko Yamamura, Shogo Minamikawa, Takashi Omori, Keita Nakanishi, Junya Fujimura, Akira Ashida, Mineaki Kitamura, Mitsuhiro Kawano, Wataru Shimabukuro, Chizuko Kitabayashi, Aya Imafuku, Keiichi Tamagaki, Koichi Kamei, Kenjirou Okamoto, Shuichiro Fujinaga, Masafumi Oka, Toru Igarashi, Akinori Miyazono, Emi Sawanobori, Rika Fujimaru, Koichi Nakanishi, Yuko Shima, Masafumi Matsuo, Ming Juan Ye, Yoshimi Nozu, Naoya Morisada, Hiroshi Kaito, Kazumoto Iijima
BACKGROUND: X-linked Alport syndrome (XLAS) is a progressive hereditary nephropathy caused by mutations in the COL4A5 gene. Genotype-phenotype correlation in male XLAS is relatively well established; relative to truncating mutations, nontruncating mutations exhibit milder phenotypes. However, transcript comparison between XLAS cases with splicing abnormalities that result in a premature stop codon and those with nontruncating splicing abnormalities has not been reported, mainly because transcript analysis is not routinely conducted in patients with XLAS...
June 29, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29959197/-gapvd1-and-ankfy1-mutations-implicate-rab5-regulation-in-nephrotic-syndrome
#19
Tobias Hermle, Ronen Schneider, David Schapiro, Daniela A Braun, Amelie T van der Ven, Jillian K Warejko, Ankana Daga, Eugen Widmeier, Makiko Nakayama, Tilman Jobst-Schwan, Amar J Majmundar, Shazia Ashraf, Jia Rao, Laura S Finn, Velibor Tasic, Joel D Hernandez, Arvind Bagga, Sawsan M Jalalah, Sherif El Desoky, Jameela A Kari, Kristen M Laricchia, Monkol Lek, Heidi L Rehm, Daniel G MacArthur, Shrikant Mane, Richard P Lifton, Shirlee Shril, Friedhelm Hildebrandt
BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of CKD. The discovery of monogenic causes of SRNS has revealed specific pathogenetic pathways, but these monogenic causes do not explain all cases of SRNS. METHODS: To identify novel monogenic causes of SRNS, we screened 665 patients by whole-exome sequencing. We then evaluated the in vitro functional significance of two genes and the mutations therein that we discovered through this sequencing and conducted complementary studies in podocyte-like Drosophila nephrocytes...
June 29, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29959196/nephrotoxicity-of-cancer-immunotherapies-past-present-and-future
#20
REVIEW
Mark A Perazella, Anushree C Shirali
Nephrotoxicity from cancer therapies is common and increasingly encountered in clinical practice, such that the subfield of "onco-nephrology" has emerged. Conventional chemotherapeutic drugs and novel agents targeting specific genes/proteins are effective cancer therapies but suffer from a number of adverse kidney effects. An effective avenue of cancer treatment is immunotherapy, which uses drugs that augment immune system-mediated recognition and targeting of tumor cells. As such, leveraging the immune system to target malignant cells represents an important modality in eradicating cancer...
June 29, 2018: Journal of the American Society of Nephrology: JASN
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