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Renal physiology

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https://www.readbyqxmd.com/read/29341964/renal-decapsulation-prevents-intrinsic-renal-compartment-syndrome-in-ischemia-reperfusion-induced-acute-kidney-injury-a-physiologic-approach
#1
Pablo Cruces, Pablo Lillo, Camila Salas, Tatiana Salomon, Felipe Lillo, Carlos González, Alejandro Pacheco, Daniel E Hurtado
OBJECTIVES: Acute kidney injury is a serious complication with unacceptably high mortality that lacks of specific curative treatment. Therapies focusing on the hydraulic behavior have shown promising results in preventing structural and functional renal impairment, but the underlying mechanisms remain understudied. Our goal is to assess the effects of renal decapsulation on regional hemodynamics, oxygenation, and perfusion in an ischemic acute kidney injury experimental model. METHODS: In piglets, intra renal pressure, renal tissue oxygen pressure, and dysoxia markers were measured in an ischemia-reperfusion group with intact kidney, an ischemia-reperfusion group where the kidney capsule was removed, and in a sham group...
February 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29341461/effect-of-immediate-and-prolonged-glp-1-receptor-agonist-administration-on-uric-acid-and-its-kidney-clearance-post-hoc-analyses-of-four-clinical-trials
#2
Lennart Tonneijck, Marcel H A Muskiet, Mark M Smits, Petter Bjornstad, Mark H H Kramer, Michaela Diamant, Ewout J Hoorn, Jaap A Joles, Daniël H van Raalte
AIMS: To determine effects of glucagon-like peptide (GLP)-1 receptor agonists (RA) on uric acid (UA)-levels and kidney UA-clearance. MATERIAL AND METHODS: Post-hoc analyses of four controlled clinical trials, which assessed actions of GLP-1RA-administration on kidney physiology. Immediate effects of GLP-1RA exenatide-infusion versus placebo was determined in 9 healthy overweight males (Study-A) and in 52 overweight T2DM-patients (Study-B). Effects were also examined of 12-week long-acting GLP-1RA liraglutide versus placebo in 36 overweight T2DM-patients (Study-C) and of 8-week short-acting GLP-1RA lixisenatide versus once-daily titrated insulin-glulisine in 35 overweight T2DM-patients (Study-D)...
January 17, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29341179/better-characterization-of-vinflunine-pharmacokinetics-variability-and-exposure-toxicity-relationship-to-improve-its-use-analyses-from-18-trials
#3
A Schmitt, L Nguyen, G Zorza, P Ferré, A Pétain
AIMS: Vinflunine is a novel tubulin-targeted inhibitor indicated as a single agent for the treatment of bladder cancers after failure of prior platinum-based therapy. Its pharmacokinetics (PK) and pharmacodynamics (PD) have been independently characterized through several phase I and phase II studies. However, no global pharmacometric analysis had been conducted yet. METHODS: Vinflunine concentrations and safety data from 18 phase I and phase II studies were used to conduct population PK and PK/PD analysis, using Nonmem...
January 17, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29339836/the-role-of-metabolic-enzymes-in-mesenchymal-tumors-and-tumor-syndromes-genetics-pathology-and-molecular-mechanisms
#4
REVIEW
Inga-Marie Schaefer, Jason L Hornick, Judith V M G Bovée
The discovery of mutations in genes encoding the metabolic enzymes isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), and fumarate hydratase (FH) has expanded our understanding not only of altered metabolic pathways but also epigenetic dysregulation in cancer. IDH1/2 mutations occur in enchondromas and chondrosarcomas in patients with the non-hereditary enchondromatosis syndromes Ollier disease and Maffucci syndrome and in sporadic tumors. IDH1/2 mutations result in excess production of the oncometabolite (D)-2-hydroxyglutarate...
January 16, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29338933/physiological-based-pharmacokinetic-modeling-to-estimate-in%C3%A2-vivo-ki-of-ketoconazole-on-renal-p-gp-using-human-drug-drug-interaction-study-result-of-fesoterodine-and-ketoconazole
#5
Masayo Oishi, Yuma Takano, Yutaka Torita, Bimal Malhotra, Koji Chiba
This study was conducted to estimate in vivo inhibition constant (Ki) of ketoconazole on renal P-glycoprotein (P-gp) using human drug-drug interaction (DDI) study result of fesoterodine and ketoconazole. Fesoterodine is a prodrug which is extensively hydrolyzed by non-specific esterases to the active metabolite 5-hydroxymethyl tolterodine (5-HMT). 5-HMT is then further metabolized via Cytochrome P450 (CYP) 2D6 and CYP3A4. It is reported that 5-HMT is a substrate of P-gp whereas fesoterodine is not. Renal clearance of 5-HMT is approximately two-times greater than renal glomerular filtration rate...
November 15, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29336060/what-the-non-nephrologist-needs-to-know-about-dialysis
#6
Matt Foy, C John Sperati
The End-Stage Renal Disease (ESRD) program now serves approximately 675,000 individuals in the United States at a cost of $26.1 billion to the Medicare system. Given the size of this population, healthcare providers from all disciplines will deliver care to patients on dialysis. Mortality remains high among patients on chronic dialysis, with 42.3% surviving 5 years. As this is a vulnerable population, it is important in the care of ESRD patients that non-nephrologists have a working knowledge of issues germane to dialysis...
January 15, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/29333144/did-creatinine-standardization-give-benefits-to-the-evaluation-of-glomerular-filtration-rate
#7
Laurence Piéroni, Anne-Sophie Bargnoux, Jean-Paul Cristol, Etienne Cavalier, Pierre Delanaye
During the last decade, a lot of efforts has been made to improve the evaluation of renal functions. Measured Glomerular Filtration Rate (GFR) remains the only valuable test to confirm or confute the status of chronic kidney disease (CKD) and is recommended by Kidney Disease Global Outcomes guidelines when estimation of GFR is not reliable. However, in routine clinical practice, serum creatinine remains the one of the most prescribed biological parameters and is an undeniable factor, alone or in association with other parameters, of the estimation of GFR...
December 2017: EJIFCC
https://www.readbyqxmd.com/read/29332180/cd39-adenosinergic-axis-in-renal-pathophysiology-and-therapeutics
#8
REVIEW
Bellamkonda K Kishore, Simon C Robson, Karen M Dwyer
Extracellular ATP interacts with purinergic type 2 (P2) receptors and elicits many crucial biological functions. Extracellular ATP is sequentially hydrolyzed to ADP and AMP by the actions of defined nucleotidases, such as CD39, and AMP is converted to adenosine, largely by CD73, an ecto-5'-nucleotidase. Extracellular adenosine interacts with P1 receptors and often opposes the effects of P2 receptor activation. The balance between extracellular ATP and adenosine in the blood and extracellular fluid is regulated chiefly by the activities of CD39 and CD73, which constitute the CD39-adenosinergic axis...
January 13, 2018: Purinergic Signalling
https://www.readbyqxmd.com/read/29329515/engaging-clinicians-and-patients-to-assess-and-improve-frailty-measurement-in-adults-with-end-stage-renal-disease
#9
Sarah Van Pilsum Rasmussen, Jonathan Konel, Fatima Warsame, Hao Ying, Brian Buta, Christine Haugen, Elizabeth King, Sandra DiBrito, Ravi Varadhan, Leocadio Rodríguez-Mañas, Jeremy D Walston, Dorry L Segev, Mara A McAdams-DeMarco
BACKGROUND: The Fried frailty phenotype, a measure of physiologic reserve defined by 5 components (exhaustion, unintentional weight loss, low physical activity, slow walking speed, and poor grip strength), is associated with poor outcomes among ESRD patients. However, these 5 components may not fully capture physiologic reserve in this population. We aimed to ascertain opinions of ESRD clinicians and patients about the usefulness of the Fried frailty phenotype and interventions to improve frailty in ESRD patients, and to identify novel components to further characterize frailty in ESRD...
January 12, 2018: BMC Nephrology
https://www.readbyqxmd.com/read/29326493/renal-mitochondria-can-withstand-hypoxic-ischemic-injury-secondary-to-renal-failure-in-uremic-rats-pretreated-with-sodium-thiosulfate
#10
Dhivya Mohan, Eswari Dhivya Balasubramanian, Sriram Ravindran, Gino A Kurian
BACKGROUND: Sodium thiosulfate (STS) is a potent drug used to treat calcific uremic arteriopathy in dialysis patients and its mode of action is envisaged by calcium chelation and antioxidant potential. STS's action on mitochondrial dysfunction, one of the major players in the pathology of vascular calcification is yet to be explored. METHODS: Adenine (0.75%, 28 days)-treated vascular calcified rat kidney was used to isolate mitochondria, where the animal was administered with or without STS for 28 days...
July 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/29322928/constraint-based-perturbation-analysis-with-cluster-newton-method-a-case-study-of-personalized-parameter-estimations-with-irinotecan-whole-body-physiologically-based-pharmacokinetic-model
#11
Shun Asami, Daisuke Kiga, Akihiko Konagaya
BACKGROUND: Drug development considering individual varieties among patients becomes crucial to improve clinical development success rates and save healthcare costs. As a useful tool to predict individual phenomena and correlations among drug characteristics and individual varieties, recently, whole-body physiologically based pharmacokinetic (WB- PBPK) models are getting more attention. WB-PBPK models generally have a lot of drug-related parameters that need to be estimated, and the estimations are difficult because the observed data are limited...
December 21, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29322409/tracking-competent-host-defence-to-chronic-inflammation-an-in-vivo-model-of-peritonitis
#12
Javier Uceda Fernandez, David Millrine, Simon A Jones
Anti-microbial host defence is dependent on the rapid recruitment of inflammatory cells to the site of infection, the elimination of invading pathogens, and the efficient resolution of inflammation so as to minimise damage to the host. The peritoneal cavity provides an easily accessible and physiologically relevant system where the delicate balance of these processes may be studied. Here, we describe murine models of peritoneal inflammation that enable studies of both competent anti-microbial immunity and inflammation associated tissue damage as a consequence of recurrent bacterial challenge...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29318961/targeting-na-k-atpase-signaling-a-new-approach-to-control-oxidative-stress
#13
Jiang Liu, Megan N Lilly, Joseph I Shapiro
Renal and cardiac function are greatly affected by chronic oxidative stress which can cause many pathophysiological states. The Na/K-ATPase is well-described as an ion pumping enzyme involved in maintaining cellular ion homeostasis; however, in the past two decades, extensive research has been done to understand the signaling function of the Na/K-ATPase and determine its role in physiological and pathophysiological states. Our lab has shown that the Na/K-ATPase signaling cascade can function as an amplifier of reactive oxygen species (ROS) which can be initiated by cardiotonic steroids or increases in ROS...
January 9, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29317843/calcium-channel-blockade-and-survival-in-recipients-of-successful-renal-transplant-an-analysis-of-the-favorit-trial-results
#14
Larry A Weinrauch, Jiankang Liu, Brian Claggett, Peter V Finn, Matthew R Weir, John A D'Elia
Introduction: Single-center and observational studies have suggested that calcium channel blocking agents may decrease the expression of sepsis in individual populations. In the renal transplant population, a role for calcium channel blockers in allograft protection and in prevention of sepsis has been postulated. We hypothesized that any important survival benefit or risk related to chronic use of calcium channel blocking agents should be discernable through an analysis of a large database of stable recipients of renal allografts who had enrolled in a large international trial...
2018: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/29307086/iron-overload-impact-on-p-atpases
#15
REVIEW
Leilismara Sousa, Marco Tulio C Pessoa, Tamara G F Costa, Vanessa F Cortes, Herica L Santos, Leandro Augusto Barbosa
Iron is a chemical element that is active in the fundamental physiological processes for human life, but its burden can be toxic to the body, mainly because of the stimulation of membrane lipid peroxidation. For this reason, the action of iron on many ATPases has been studied, especially on P-ATPases, such as the Na+,K+-ATPase and the Ca2+-ATPase. On the Fe2+-ATPase activity, the free iron acts as an activator, decreasing the intracellular Fe2+ and playing a protection role for the cell. On the Ca2+-ATPase activity, the iron overload decreases the enzyme activity, raising the cytoplasmic Ca2+ and decreasing the sarco/endoplasmic reticulum and the Golgi apparatus Ca2+ concentrations, which could promote an enzyme oxidation, nitration, and fragmentation...
January 6, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29305327/renal-tubular-damage-caused-by-cylindrospermopsin-cyanotoxin-in-mice
#16
A C N Moraes, V F Magalhães
Cylindrospermopsin (CYN) is a cyanotoxin and a hydrophilic alkaloid of 415 Da. The principal effect of CYN is the inhibition of protein synthesis, and it can damage various organs. Studies have demonstrated that the kidney is the most affected organ. CYN has played roles in at least two poisoning cases, i.e., the mysterious Palm Island disease in Australia and the event at Caruaru in Brazil. Therefore, we aimed to determine how CYN disrupts the renal tissue. Dose-response curves following single intraperitoneal injections of purified CYN (at 0, 16, 32, 64 and 128 μg CYN/kg body weight) were created in 10-week-old male BALB/C mice (n = 4)...
January 2, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29303965/non-invasive-renal-perfusion-imaging-using-arterial-spin-labeling-mri-challenges-and-opportunities
#17
REVIEW
Fabio Nery, Isky Gordon, David L Thomas
Tissue perfusion allows for delivery of oxygen and nutrients to tissues, and in the kidneys is also a key determinant of glomerular filtration. Quantification of regional renal perfusion provides a potential window into renal (patho) physiology. However, non-invasive, practical, and robust methods to measure renal perfusion remain elusive, particularly in the clinic. Arterial spin labeling (ASL), a magnetic resonance imaging (MRI) technique, is arguably the only available method with potential to meet all these needs...
January 5, 2018: Diagnostics
https://www.readbyqxmd.com/read/29301788/cardiac-endothelial-cell-transcriptome
#18
Achim Lother, Stella Bergemann, Lisa Deng, Martin Moser, Christoph Bode, Lutz Hein
OBJECTIVE: Endothelial cells (ECs) are a highly specialized cell type with marked diversity between different organs or vascular beds. Cardiac ECs are an important player in cardiac physiology and pathophysiology but are not sufficiently characterized yet. Thus, the aim of the present study was to analyze the cardiac EC transcriptome. APPROACH AND RESULTS: We applied fluorescence-assisted cell sorting to isolate pure ECs from adult mouse hearts. RNAseq revealed 1288 genes predominantly expressed in cardiac ECs versus heart tissue including several transcription factors...
January 4, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29301417/isolated-kidney-perfusion-the-influence-of-pulsatile-flow
#19
Charlotte von Horn, Thomas Minor
Within the scope of transplantation research, ex vivo kidney perfusion has been proven an attractive model to study ischemia-reperfusion and preservation injury. Renal perfusion techniques also occupy scientists with the aim to optimize organ reconditioning and preparation prior to transplantation. This study investigated the influence of a pulsatile perfusion pattern that brings flow conditions closer to physiological situations, on renal perfusion characteristic and kidney function in the isolated perfused kidney...
January 4, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/29298795/cardiac-tamponade-causing-severe-reversible-hyponatraemia
#20
Tarun Dalia, Reza Masoomi, Kamal Kant Sahu, Kamal Gupta
Severe hyponatraemia in setting of cardiac tamponade is very rare and only few case reports have been reported so far. This case report highlights pericardial tamponade as a rare but easily treatable cause of severe hyponatraemia. Pertinent literature is also reviewed. A 70-year-old woman presented to the emergency department with altered mental status. She was tachycardic and hypotensive with cardiomegaly on a chest X-ray. Serum sodium was severely low at 109 mmol/L and was identified as the likely cause for her abnormal mentation...
January 3, 2018: BMJ Case Reports
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