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Kidney International

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https://www.readbyqxmd.com/read/28416226/klotho-restoration-via-acetylation-of-peroxisome-proliferation-activated-receptor-%C3%AE-reduces-the-progression-of-chronic-kidney-disease
#1
Wenjun Lin, Qin Zhang, Lin Liu, Shasha Yin, Zhihong Liu, Wangsen Cao
Klotho is an anti-aging protein mainly expressed in the kidney. Reduced Klotho (1) expression closely correlates with the development and progression of chronic kidney disease (CKD). Klotho is also a downstream gene of Peroxisome Proliferation-Activated Receptor γ (PPARγ), a major transcription factor whose functions are significantly affected by post-translational modifications including acetylation. However, whether PPARγ acetylation regulates renal Klotho expression and function in CKD is unknown. Here we test whether renal damage and reduced Klotho expression in the adenine CKD mouse model can be attenuated by the pan histone deacetylase (HDAC) inhibitor trichostatin A...
April 14, 2017: Kidney International
https://www.readbyqxmd.com/read/28416225/b-type-natriuretic-peptide-overexpression-ameliorates-hepatorenal-fibrocystic-disease-in%C3%A2-a%C3%A2-rat%C3%A2-model-of-polycystic-kidney-disease
#2
Sara J Holditch, Claire A Schreiber, Peter C Harris, Nicholas F LaRusso, Marina Ramirez-Alvarado, Alessandro Cataliotti, Vicente E Torres, Yasuhiro Ikeda
Polycystic kidney disease (PKD) involves progressive hepatorenal cyst expansion and fibrosis, frequently leading to end-stage renal disease. Increased vasopressin and cAMP signaling, dysregulated calcium homeostasis, and hypertension play major roles in PKD progression. The guanylyl cyclase A agonist, B-type natriuretic peptide (BNP), stimulates cGMP and shows anti-fibrotic, anti-hypertensive, and vasopressin-suppressive effects, potentially counteracting PKD pathogenesis. Here, we assessed the impacts of guanylyl cyclase A activation on PKD progression in a rat model of PKD...
April 14, 2017: Kidney International
https://www.readbyqxmd.com/read/28416224/post-discharge-kidney-function-is-associated-with-subsequent-ten-year-renal-progression-risk-among-survivors-of-acute-kidney-injury
#3
Simon Sawhney, Angharad Marks, Nick Fluck, Adeera Levin, David McLernon, Gordon Prescott, Corri Black
The extent to which renal progression after acute kidney injury (AKI) arises from an initial step drop in kidney function (incomplete recovery), or from a long-term trajectory of subsequent decline, is unclear. This makes it challenging to plan or time post-discharge follow-up. This study of 14651 hospital survivors in 2003 (1966 with AKI, 12685 no AKI) separates incomplete recovery from subsequent renal decline by using the post-discharge estimated glomerular filtration rate (eGFR) rather than the pre-admission as a new reference point for determining subsequent renal outcomes...
April 14, 2017: Kidney International
https://www.readbyqxmd.com/read/28412022/acute-kidney-injury-is-associated-with-microvascular-myocardial-damage-following-myocardial-infarction
#4
Sebastian Johannes Reinstadler, Andreas Kronbichler, Martin Reindl, Hans-Josef Feistritzer, Veronika Innerhofer, Agnes Mayr, Gert Klug, Martin Tiefenthaler, Gert Mayer, Bernhard Metzler
Acute kidney injury (AKI) is a frequent complication in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention. However, the pathophysiology of AKI in this setting is complex and goes beyond the administration of contrast media. Studies assessing the impact of infarct characteristics on AKI are currently lacking. Therefore, we investigated the association of AKI with myocardial as well as microvascular injury in an initial total of 361 consecutive STEMI patients treated by primary percutaneous coronary intervention...
April 12, 2017: Kidney International
https://www.readbyqxmd.com/read/28412021/prediction-and-validation-of-the-duration-of-hemodialysis-sessions-for-the-treatment-of-acute-ethylene-glycol-poisoning
#5
Ioan-Andrei Iliuta, Philippe Lachance, Marc Ghannoum, Yannick Bégin, Fabrice Mac-Way, Simon Desmeules, Sacha A De Serres, Anne-Sophie Julien, Pierre Douville, Mohsen Agharazii
The duration of hemodialysis (HD) sessions for the treatment of acute ethylene glycol poisoning is dependent on concentration, the operational parameters used during HD, and the presence and severity of metabolic acidosis. Ethylene glycol assays are not readily available, potentially leading to undue extension or premature termination of HD. We report a prediction model for the duration of high-efficiency HD sessions based retrospectively on a cohort study of 26 cases of acute ethylene glycol poisoning in 24 individuals treated by alcohol dehydrogenase competitive inhibitors, cofactors and HD...
April 12, 2017: Kidney International
https://www.readbyqxmd.com/read/28412020/cardiac-surgery-in-patients-with-congenital-heart-disease-is-associated-with-acute-kidney-injury-and-the-risk-of-chronic-kidney-disease
#6
Nicolas L Madsen, Stuart L Goldstein, Trine Frøslev, Christian F Christiansen, Morten Olsen
Cardiac surgery associated-acute kidney injury (CS-AKI) occurs in 30-50% of patients undergoing surgery for congenital heart disease. Here we determine if CS-AKI is associated with chronic kidney disease (CKD) in patients with congenital heart disease. Using Danish regional population-based registries, our cohort study included patients with congenital heart disease born between 1990-2010 with first cardiac surgery between 2005 and 2010 (under 15 years of age). Utilizing in- and out-patient laboratory serum creatinine data, we identified individuals fulfilling KDIGO stages of AKI within 5 days of cardiac surgery...
April 12, 2017: Kidney International
https://www.readbyqxmd.com/read/28412019/renal-function-in-relation-to-sodium-intake-a%C3%A2-quantitative-review-of-the-literature
#7
REVIEW
Kyoko Nomura, Kei Asayama, Lotte Jacobs, Lutgarde Thijs, Jan A Staessen
We undertook a quantitative literature review to search for evidence underpinning current guidelines proposing a reduction of sodium intake to less than 2.4 g/d for the management of chronic kidney disease. We searched PubMed for peer-reviewed articles published from January 1980 through May 2016. Two investigators screened 5072 publications and extracted data from 36, including 11 cross-sectional and 5 longitudinal observational studies and 20 intervention trials. Within-study effect sizes were pooled and standardized to a sodium gradient of 100 mmol/d by using inverse-variance weighted random effects models...
April 12, 2017: Kidney International
https://www.readbyqxmd.com/read/28396123/unique-hemoglobin-a1c-level-distribution-and-its-relationship-with-mortality-in-diabetic-hemodialysis-patients
#8
Junichi Hoshino, Maria Larkina, Angelo Karaboyas, Brian A Bieber, Yoshifumi Ubara, Kenmei Takaichi, Tadao Akizawa, Takashi Akiba, Shunichi Fukuhara, Ronald L Pisoni, Akira Saito, Bruce M Robinson
Diabetic hemodialysis patients with hemoglobin A1c (HbA1c) levels below 6.5% and over 8.0% face a higher mortality risk. To determine the optimal glycemic control in Japanese patients, we examined the association between HbA1c and mortality in 2,300 Japanese diabetic patients on maintenance hemodialysis with HbA1c levels determined at enrollment in the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS) phases 2-5, using Cox regression analysis with adjustment for baseline age, sex, dialysis vintage, 12 general comorbidities, hemoglobin, albumin and creatinine levels, and insulin use; stratification by JDOPPS phase; and facility clustering taken into account...
April 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28396122/evaluation-of-the-impact-of-gut-microbiota-on-uremic-solute-accumulation-by-a-ce-tofms-based-metabolomics-approach
#9
Eikan Mishima, Shinji Fukuda, Chikahisa Mukawa, Akinori Yuri, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yasutoshi Akiyama, Noriko N Fukuda, Hiroki Tsukamoto, Kei Asaji, Hisato Shima, Koichi Kikuchi, Chitose Suzuki, Takehiro Suzuki, Yoshihisa Tomioka, Tomoyoshi Soga, Sadayoshi Ito, Takaaki Abe
Gut microbiota is involved in the metabolism of uremic solutes. However, the precise influence of microbiota to the retention of uremic solutes in CKD is obscure. To clarify this, we compared adenine-induced renal failure and control mice under germ-free or specific pathogen-free (SPF) conditions, examining the metabolite profiles of plasma, feces, and urine using a capillary electrophoresis time-of-flight mass spectrometry-based approach. Mice with renal failure under germ-free conditions demonstrated significant changes in plasma metabolites...
April 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28396121/antagonism-of-profibrotic-microrna-21-improves%C3%A2-outcome-of-murine-chronic-renal-allograft-dysfunction
#10
Celina Schauerte, Anika Hübner, Song Rong, Shijun Wang, Nelli Shushakova, Michael Mengel, Angela Dettling, Claudia Bang, Kristian Scherf, Malte Koelling, Anette Melk, Hermann Haller, Thomas Thum, Johan M Lorenzen
Chronic renal allograft dysfunction (CAD) is a major limiting factor of long-term graft survival. It is characterized by interstitial fibrosis and tubular atrophy. The underlying pathomechanisms are incompletely understood. MicroRNAs are powerful regulators of gene expression and may have an impact on various diseases by direct mRNA decay or translational inhibition. A murine model of allogenic kidney transplantation was used resulting in CAD at 6 weeks after kidney transplantation. We identified fibrosis-associated miR-21a-5p by whole miRNAome expression analysis to be among the most highly upregulated miRNAs...
April 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28396120/klotho-expression-in-osteocytes-regulates-bone-metabolism-and-controls-bone-formation
#11
Hirotaka Komaba, Jovana Kaludjerovic, Dorothy Z Hu, Kenichi Nagano, Katsuhiko Amano, Noriko Ide, Tadatoshi Sato, Michael J Densmore, Jun-Ichi Hanai, Hannes Olauson, Teresita Bellido, Tobias E Larsson, Roland Baron, Beate Lanske
Osteocytes within the mineralized bone matrix control bone remodeling by regulating osteoblast and osteoclast activity. Osteocytes express the aging suppressor Klotho, but the functional role of this protein in skeletal homeostasis is unknown. Here we identify Klotho expression in osteocytes as a potent regulator of bone formation and bone mass. Targeted deletion of Klotho from osteocytes led to a striking increase in bone formation and bone volume coupled with enhanced osteoblast activity, in sharp contrast to what is observed in Klotho hypomorphic (kl/kl) mice...
April 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28396119/interferon-%C3%AE-production-by-tubulointerstitial-human-cd56-bright-natural-killer-cells-contributes-to-renal-fibrosis-and-chronic-kidney-disease-progression
#12
Becker M P Law, Ray Wilkinson, Xiangju Wang, Katrina Kildey, Mae Lindner, Melissa J Rist, Kenneth Beagley, Helen Healy, Andrew J Kassianos
Natural killer (NK) cells are a population of lymphoid cells that play a significant role in mediating innate immune responses. Studies in mice suggest a pathological role for NK cells in models of kidney disease. In this study, we characterized the NK cell subsets present in native kidneys of patients with tubulointerstitial fibrosis, the pathological hallmark of chronic kidney disease. Significantly higher numbers of total NK cells (CD3(-)CD56(+)) were detected in renal biopsies with tubulointerstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue using multi-color flow cytometry...
April 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28396117/the-p2x7-receptor-antagonist-oxidized-adenosine%C3%A2-triphosphate-ameliorates-renal-ischemia-reperfusion-injury-by-expansion-of-regulatory-t%C3%A2-cells
#13
Tai Yeon Koo, Jae-Ghi Lee, Ji-Jing Yan, Joon Young Jang, Kyung Don Ju, Miyeun Han, Kook-Hwan Oh, Curie Ahn, Jaeseok Yang
Extracellular adenosine triphosphate (ATP) binds to purinergic receptors and, as a danger molecule, promotes inflammatory responses. Here we tested whether periodate-oxidized ATP (oATP), a P2X7 receptor (P2X7R) antagonist can attenuate renal ischemia-reperfusion injury and clarify the related cellular mechanisms. Treatment with oATP prior to ischemia-reperfusion injury decreased blood urea nitrogen, serum creatinine, the tubular injury score, and tubular epithelial cell apoptosis after injury. The infiltration of dendritic cells, neutrophils, macrophages, CD69(+)CD4(+), and CD44(+)CD4(+) T cells was attenuated, but renal Foxp3(+)CD4(+) Treg infiltration was increased by oATP...
April 8, 2017: Kidney International
https://www.readbyqxmd.com/read/28396118/superoxide-and-hydrogen-peroxide-counterregulate-myogenic-contractions-in-renal-afferent-arterioles-from-a-mouse-model-of-chronic-kidney-disease
#14
Lingli Li, En Yin Lai, Zaiming Luo, Glenn Solis, Kathy K Griendling, W Robert Taylor, Pedro A Jose, Anton Wellsten, William J Welch, Christopher S Wilcox
Myogenic contractions protect kidneys from barotrauma but are impaired in chronic kidney disease (CKD). Since myogenic contractions are enhanced by superoxide but impaired by hydrogen peroxide, we tested the hypothesis that they are counterregulated by superoxide and H2O2 from NOX2/p47phox and/or NOX4/POLDIP2 in CKD. Myogenic contraction in isolated perfused afferent arterioles from mice with surgical 5/6 nephrectomy or sham operations fed a 6% sodium chloride diet was measured directly while superoxide and H2O2 were measured by fluorescence microscopy...
April 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28396116/beta-2-adrenergic-receptor-agonists-are-novel-regulators-of-macrophage-activation-in-diabetic-renal-and-cardiovascular-complications
#15
Hyunjin Noh, Mi Ra Yu, Hyun Joo Kim, Ji Hye Lee, Byoung-Won Park, I-Hsien Wu, Motonobu Matsumoto, George L King
Macrophage activation is increased in diabetes and correlated with the onset and progression of vascular complications. To identify drugs that could inhibit macrophage activation, we developed a cell-based assay and screened a 1,040 compound library for anti-inflammatory effects. Beta2-adrenergic receptor (β2AR) agonists were identified as the most potent inhibitors of phorbol myristate acetate-induced tumor necrosis factor-α production in rat bone marrow macrophages. In peripheral blood mononuclear cells isolated from streptozotocin-induced diabetic rats, β2AR agonists inhibited diabetes-induced tumor necrosis factor-α production, which was prevented by co-treatment with a selective β2AR blocker...
April 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28396115/improved-clinical-trial-enrollment-criterion-to-identify-patients-with-diabetes-at-risk-of-end-stage-renal-disease
#16
Masayuki Yamanouchi, Jan Skupien, Monika A Niewczas, Adam M Smiles, Alessandro Doria, Robert C Stanton, Andrzej T Galecki, Kevin L Duffin, Nick Pullen, Matthew D Breyer, Joseph V Bonventre, James H Warram, Andrzej S Krolewski
Design of Phase III trials for diabetic nephropathy currently requires patients at a high risk of progression defined as within three years of a hard end point (end-stage renal disease, 40% loss of estimated glomerular filtration rate, or death). To improve the design of these trials, we used natural history data from the Joslin Kidney Studies of chronic kidney disease in patients with diabetes to develop an improved criterion to identify such patients. This included a training cohort of 279 patients with type 1 diabetes and 134 end points within three years, and a validation cohort of 221 patients with type 2 diabetes and 88 end points...
April 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28385297/renal-tubular-nhe3-is-required-in-the-maintenance-of-water-and-sodium-chloride-homeostasis
#17
Robert A Fenton, Søren B Poulsen, Samantha de la Mora Chavez, Manoocher Soleimani, Jessica A Dominguez Rieg, Timo Rieg
The sodium/proton exchanger isoform 3 (NHE3) is expressed in the intestine and the kidney, where it facilitates sodium (re)absorption and proton secretion. The importance of NHE3 in the kidney for sodium chloride homeostasis, relative to the intestine, is unknown. Constitutive tubule-specific NHE3 knockout mice (NHE3(loxloxCre)) did not show significant differences compared to control mice in body weight, blood pH or bicarbonate and plasma sodium, potassium, or aldosterone levels. Fluid intake, urinary flow rate, urinary sodium/creatinine, and pH were significantly elevated in NHE3(loxloxCre) mice, while urine osmolality and GFR were significantly lower...
April 3, 2017: Kidney International
https://www.readbyqxmd.com/read/28366228/albuminuria-and-posttransplant-chronic-kidney-disease-stage-predict-transplant-outcomes
#18
Ngan N Lam, Marcello Tonelli, Krista L Lentine, Brenda Hemmelgarn, Feng Ye, Kevin Wen, Scott Klarenbach
In 2012, the KDIGO guidelines updated the classification system for chronic kidney disease to include albuminuria. Whether this classification system predicts adverse clinical outcomes among kidney transplant recipients is unclear. To evaluate this, we conducted a retrospective study using linked databases in Alberta, Canada to follow kidney transplant recipients from 2002-2011. We examined the association between an estimated glomerular filtration rate (eGFR of 60 or more, 45-59, 30-44, 15-29 mL/min/1.73 m(2)) and albuminuria (normal, mild, heavy) at one year post-transplant and subsequent mortality and graft loss...
March 30, 2017: Kidney International
https://www.readbyqxmd.com/read/28366227/fast-renal-decline-to-end-stage-renal-disease-an-unrecognized-feature-of-nephropathy-in-diabetes
#19
REVIEW
Andrzej S Krolewski, Jan Skupien, Peter Rossing, James H Warram
A new model of diabetic nephropathy in type 1 diabetes emerged from our studies of Joslin Clinic patients. The dominant feature is progressive renal decline, not albuminuria. This decline is a unidirectional process commencing while patients have normal renal function and, in the majority, progressing steadily (linearly) to end-stage renal disease (ESRD). While an individual's rate of renal decline is constant, the estimated glomerular filtration rate (eGFR) slope varies widely among individuals from -72 to -3...
March 30, 2017: Kidney International
https://www.readbyqxmd.com/read/28359537/macrophage-density-in-early-surveillance-biopsies-predicts-future-renal-transplant-function
#20
Jan Hinrich Bräsen, Abedalrazag Khalifa, Jessica Schmitz, Wei Dai, Gunilla Einecke, Anke Schwarz, Michael Hallensleben, Bernhard M W Schmidt, Hans H Kreipe, Hermann Haller, Sibylle von Vietinghoff
Inflammation impairs renal allograft survival but is difficult to quantify by eye at low densities. Here we measured leukocyte abundance in early surveillance biopsies by digital image analysis to test for a role of chemokine receptor genotypes and analyze the predictive value of leukocyte subsets to allograft function. In six-week surveillance biopsies, T-cell (CD3), B-cell (CD20), macrophage (CD68), and dendritic cell (CD209) densities were assessed in whole slide scans. Renal cortical CD3, CD20, and CD68 were significantly higher in histologic rejection...
March 27, 2017: Kidney International
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