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https://www.readbyqxmd.com/read/28339149/effect-of-food-intake-on-the-pharmacodynamics-of-tenapanor-a-phase-1-study
#1
Susanne A Johansson, Mikael Knutsson, Maria Leonsson-Zachrisson, David P Rosenbaum
Tenapanor (RDX5791/AZD1722) is a minimally systemic small-molecule inhibitor of the sodium/hydrogen exchanger NHE3. Tenapanor acts in the gut to reduce absorption of sodium and phosphate. This phase 1 open-label, 3-way crossover study (NCT02226783) evaluated the effect of food on the pharmacodynamics of tenapanor. Eighteen volunteers completed a randomized sequence of three 4-day treatments with tenapanor hydrochloride 15 mg twice daily: before food, after food, and while fasting. Participants received a diet standardized for sodium content...
March 24, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28336818/increased-exposure-to-sodium-during-pregnancy-and-lactation-changes-basal-and-induced-behavioral-and-neuroendocrine-responses-in-adult-male-offspring
#2
Marcia S Silva, Fabiana Lúcio-Oliveira, Andre Souza Mecawi, Lucas F Almeida, Silvia G Ruginsk, Michael P Greenwood, Mingkwan Greenwood, Laura Vivas, Lucila L K Elias, David Murphy, José Antunes-Rodrigues
Excessive sodium (Na(+)) intake in modern society has been associated with several chronic disorders such as hypertension. Several studies suggest that early life events can program physiological systems and lead to functional changes in adulthood. Therefore, we investigated behavioral and neuroendocrine responses under basal conditions and after 48 h of water deprivation in adult (60-day-old Wistar rats) male, Wistar rats originating from dams were offered only water or 0.15 mol/L NaCl during pregnancy and lactation...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28332143/the-relationship-between-increases-in-morning-spot-urinary-glucose-excretion-and-decreases-in-hba1c-in-patients-with-type-2-diabetes-after-taking-an-sglt2-inhibitor-a-retrospective-longitudinal-study
#3
So Ra Kim, Yong-Ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors increase urinary glucose excretion (UGE) by reducing the renal threshold for glucose excretion, which results in decreased serum glucose concentrations in patients with type 2 diabetes mellitus (T2D). However, no study to date has determined whether larger increases in UGE after SGLT2 inhibitor treatment correspond to larger reductions in glycated hemoglobin (HbA1C). METHODS: We enrolled participants who were newly prescribed an SGLT2 inhibitor (dapagliflozin 10 mg or ipragliflozin 50 mg, once daily) as an add-on therapy...
March 22, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28331937/whey-protein-and-albumin-effects-upon-urinary-risk-factors-for-stone-formation
#4
Camila Mithie Hattori, Hans-Göran Tiselius, Ita Pfeferman Heilberg
Protein supplements are consumed for an expected increase in muscle mass and improved exercise performance, but as their impact on lithogenic parameters are unknown, we aimed to evaluate the effects of Whey protein (WP) and Albumin upon the risk factors for nephrolithiasis. WP or Albumin supplements (one scoop/day) were administered for 3 days to 18 healthy volunteers, with 1-week washout period between them. Serum and 24-h urine samples were collected at baseline and after completing each intervention. All participants were asked to replicate their baseline diet during the subsequent urine collection...
March 22, 2017: Urolithiasis
https://www.readbyqxmd.com/read/28325783/renal-handling-of-ketones-in-response-to-sodium-glucose-cotransporter-2-inhibition-in-patients-with-type-2-diabetes
#5
Ele Ferrannini, Simona Baldi, Silvia Frascerra, Brenno Astiarraga, Elisabetta Barsotti, Aldo Clerico, Elza Muscelli
OBJECTIVE: Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release, including decrements in plasma glucose and insulin levels, increments in glucagon release, enhanced lipolysis, and stimulation of ketogenesis, resulting in an increase in ketonemia. We aimed at assessing the renal response to these changes. RESEARCH DESIGN AND METHODS: We measured fasting and postmeal urinary excretion of glucose, β-hydroxybutyrate (β-HB), lactate, and sodium in 66 previously reported patients with type 2 diabetes and preserved renal function (estimated glomerular filtration rate ≥60 mL · min(-1) · 1...
March 21, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28324033/effect-of-moxonidine-on-the-aldosterone-renin-ratio-in-healthy-male-volunteers
#6
Ashraf H Ahmed, Richard D Gordon, Gregory Ward, Martin Wolley, Brett C McWhinney, Jacobus P Ungerer, Michael Stowasser
Background: The most popular screening test for primary aldosteronism (PA) is the plasma aldosterone/ renin ratio (ARR). Medications, dietary sodium, posture and time of day all affect renin and aldosterone levels, and can result in false negative or positive ARRs if not controlled. Most antihypertensive medications affect the ARR and can interfere with interpretation of results. To our knowledge, no study has been undertaken to evaluate the effects of moxonidine on the ARR. Methods: Normotensive, non-medicated male volunteers (n=20) underwent measurement (seated, midmorning) of plasma aldosterone (by HPLC-tandem mass spectrometry), direct renin concentration (DRC), renin activity (PRA), cortisol, electrolytes and creatinine and urinary aldosterone, cortisol, electrolytes and creatinine at baseline, and after one week of moxonidine at 0...
March 16, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28324025/clinical-and-genetic-features-of-patients-with-type-2-diabetes-and-renal-glycosuria
#7
Siqian Gong, Jiandong Guo, Xueyao Han, Meng Li, Lingli Zhou, Xiaoling Cai, Yu Zhu, Yingying Luo, Simin Zhang, Xianghai Zhou, Yumin Ma, Linong Ji
Context: A sodium glucose cotransporter 2 (SGLT2) inhibitor, which increases urinary glucose excretion, was recently reported to decrease blood glucose levels and deaths among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease. Mutations in SLC5A2 and HNF1A are associated with renal glycosuria, but their contributions to renal glycosuria in patients with T2DM are not well understood. Objective: To assess the clinical features of T2DM patients with renal glycosuria and those with low urinary glucose excretion (LUGE) and identify variants in the coding regions of SLC5A2 and HNF1A in patients with renal glycosuria and T2DM...
January 26, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28322418/associations-of-sodium-potassium-and-protein-intake-with-blood-pressure-and-hypertension-in-switzerland
#8
Nicolas Glatz, Aline Chappuis, David Conen, Paul Erne, Antoinette Péchère-Bertschi, Idris Guessous, Valentina Forni, Luca Gabutti, Franco Muggli, Augusto Gallino, Daniel Hayoz, Isabelle Binet, Paolo Suter, Fred Paccaud, Murielle Bochud, Michel Burnier
BACKGROUND: Nutritional factors play an important role in the regulation of blood pressure and in the development of hypertension. In this analysis, we explored the associations of 24-hour urinary Na+, K+ and urea excretion with blood pressure levels and the risk of hypertension in the Swiss population, taking regional linguistic differences into account. METHODS: The Swiss Survey on Salt is a population based cross-sectional study that included 1336 subjects from the three main linguistic regions (French, German and Italian) of Switzerland...
March 21, 2017: Swiss Medical Weekly
https://www.readbyqxmd.com/read/28321056/sodium-glucose-co-transporter-2-inhibitors-reduce-the-abdominal-visceral-fat-area-and-may-influence-the-renal-function-in-patients-with-type-2-diabetes
#9
Takahiro Tosaki, Hideki Kamiya, Tatsuhito Himeno, Yoshiro Kato, Masaki Kondo, Kaori Toyota, Tomoyo Nishida, Megumi Shiroma, Kaori Tsubonaka, Hitomi Asai, Miho Moribe, Yuki Nakaya, Jiro Nakamura
Objective and Methods An SGLT2 inhibitor (ipragliflozin, dapagliflozin, luseogliflozin, tofogliflozin, or canagliflozin) was administered to 132 outpatients with type 2 diabetes mellitus with or without other antidiabetic drugs for 6 months to evaluate its efficacy, the incidence of adverse events, and its influence on the renal function. Results The patient's mean glycated hemoglobin level significantly improved from 7.52±1.16% to 6.95±0.98% (p<0.001). The body weight of the patients was significantly reduced from 78...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28321001/comparative-effects-of-an-angiotensin-ii-receptor-blocker-arb-diuretic-vs-arb-calcium-channel-blocker-combination-on-uncontrolled-nocturnal-hypertension-evaluated-by-information-and-communication-technology-based-nocturnal-home-blood-pressure-monitoring%C3%A3-the
#10
Kazuomi Kario, Naoko Tomitani, Hiroshi Kanegae, Hajime Ishii, Kazuaki Uchiyama, Kayo Yamagiwa, Toshihiko Shiraiwa, Tomohiro Katsuya, Tetsuro Yoshida, Kiyomi Kanda, Shinji Hasegawa, Satoshi Hoshide
BACKGROUND: Nocturnal blood pressure (BP) is an independent risk factor of cardiovascular events. The NOCTURNE study, a multicenter, randomized controlled trial (RCT) using our recently developed information and communication technology (ICT) nocturnal home BP monitoring (HBPM) device, was performed to compare the nocturnal HBP-lowering effects of differential ARB-based combination therapies in 411 Japanese patients with nocturnal hypertension (HT).Methods and Results:Patients with nocturnal BP ≥120/70 mmHg at baseline even under ARB therapy (100 mg irbesartan daily) were enrolled...
March 17, 2017: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/28314642/hypotensive-effects-of-renal-denervation-in-spontaneously-hypertensive-rat-based-on-ultrasonic-contrast-imaging
#11
Ke Li, Jinwen Tian, Yuxiao Zhang, Qiao Xue, Caiyi Lu
BACKGROUND: Sympathetic nerves-fire rate is generally enhanced in some types of hypertension models. Renal sympathetic denervation(RSD) by the radiofrequency ablation was used to treat the hypertension has achieved curative effect.HTN-1 and HTN-2 trial reported catheter-based renal denervation may cause substantial and sustained blood-pressure reduction in patients with resistant hypertension. However, recent controlled HTN-3 trial questioned the BP lowering effect of Renal denervation treatment...
February 9, 2017: Computerized Medical Imaging and Graphics: the Official Journal of the Computerized Medical Imaging Society
https://www.readbyqxmd.com/read/28303514/euglycemic-ketosis-in-patients-with-type-2-diabetes-on-sglt2-inhibitor-therapy-an-emerging-problem-and-solutions-offered-by-diabetes-technology
#12
A Pfützner, D Klonoff, L Heinemann, N Ejskjaer, J Pickup
Diabetic ketoacidosis is an infrequent but life-threatening acute complication of diabetes, affecting predominantly patients with type 1 diabetes, children, and pregnant women, where ketosis is usually associated with marked hyperglycemia. Recently, an increasing number of cases have been reported of euglycemic diabetic ketoacidosis in patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitor treatment in routine practice. There is a minor, but not negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials...
March 17, 2017: Endocrine
https://www.readbyqxmd.com/read/28302903/differential-effects-of-dapagliflozin-on-cardiovascular-risk-factors-at-varying-degrees-of-renal-function
#13
Sergei Petrykiv, C David Sjöström, Peter J Greasley, John Xu, Frederik Persson, Hiddo J L Heerspink
BACKGROUND AND OBJECTIVE: Sodium glucose cotransporter 2 inhibition with dapagliflozin decreases hemoglobin A1c (HbA1c), body weight, BP, and albuminuria (urinary albumin-to-creatinine ratio). Dapagliflozin also modestly increases hematocrit, likely related to osmotic diuresis/natriuresis. Prior studies suggest that the HbA1c-lowering effects of dapagliflozin attenuate at lower eGFR. However, effects on other cardiovascular risk factors at different eGFR levels are incompletely understood...
March 16, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28299764/bolus-injection-versus-infusion-of-furosemide-in-kidney-transplantation-a-randomized-clinical-trial
#14
Afshar Zomorrodi, Hassan Mohammadipoor Anvari, Farzad Kakaei, Farzin Solymanzadeh, Esmaeil Khanlari, Amin Bagheri
PURPOSE: Furosemide is commonly administered to increase the urinary output in patients with transplanted kidneys. This study compared the two administration routes of furosemide (bolus versus infusion) in kidney transplanted patients. MATERIALS AND METHODS: Fifty patients who had undergone kidney transplantation in 2015 in a hospital in Tabriz, Iran, were included in this clinical trial. They were divided into two groups: bolus (120 mg stat) and infusion (4 mg/minute) groups...
March 16, 2017: Urology Journal
https://www.readbyqxmd.com/read/28298361/intrarenal-signaling-mediated-by-cck-plays-a-role-in-salt-intake-induced-natriuresis
#15
Hiromi Takahashi-Iwanaga, Shunsuke Kimura, Kohtarou Konno, Masahiko Watanabe, Toshihiko Iwanaga
The natriuretic hormone CCK exhibits its gene transcripts in total kidney extracts. To test the possibility of CCK acting as an intrarenal mediator of sodium excretion, we examined mouse kidneys by: (i) an in situ hybridization technique for CCK mRNA in animals fed a normal or a high-sodium diet; (ii) immuno-electron microscopy for the CCK peptide, (iii) an in situ hybridization method and immunohistochemistry for the CCK-specific receptor CCKAR; (iv) confocal image analysis of receptor-mediated Ca2+ responses in isolated renal tubules; and (v) metabolic cage experiments for the measurement of urinary sodium excretion in high salt-fed mice either treated or untreated with the CCKAR antagonist lorglumide...
March 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28295959/the-albuminuria-lowering-response-to-dapagliflozin-is-variable-and-reproducible-between-individual-patients
#16
Sergei I Petrykiv, Gozewijn D Laverman, Dick de Zeeuw, Hiddo J L Heerspink
AIMS: Albuminuria reduction is essential for renal and cardiovascular protection. We characterized the efficacy of dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, on albuminuria. Secondly, we assessed whether the albuminuria lowering effect varies between patients, and whether this variability in response is reproducible. MATERIAL AND METHODS: A double-blind, randomized, placebo controlled crossover trial was conducted. Patients with type 2 diabetes and albumin:creatinine ratio >100 mg/g on a stable dose of an Angiotensin Converting Enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) were enrolled...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28293641/functional-effects-of-prebiotic-fructans-in-colon-cancer-and-calcium-metabolism-in-animal-models
#17
Marisol Rivera-Huerta, Vania Lorena Lizárraga-Grimes, Ibrahim Guillermo Castro-Torres, Mabel Tinoco-Méndez, Lucía Macías-Rosales, Francisco Sánchez-Bartéz, Graciela Guadalupe Tapia-Pérez, Laura Romero-Romero, María Isabel Gracia-Mora
Inulin-type fructans are polymers of fructose molecules and are known for their capacity to enhance absorption of calcium and magnesium, to modulate gut microbiota and energy metabolism, and to improve glycemia. We evaluated and compared the effects of Chicory inulin "Synergy 1®" and inulin from Mexican agave "Metlin®" in two experimental models of colon cancer and bone calcium metabolism in mice and rats. Inulins inhibited the development of dextran sulfate sodium-induced colitis and colon cancer in mice; these fructans reduced the concentration of tumor necrosis factor alpha and prevented the formation of intestinal polyps, villous atrophy, and lymphoid hyperplasia...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28289184/renal-tubular-ubiquitin-protein-ligase-nedd4-2-is-required-for-renal-adaptation-during-long-term-potassium-depletion
#18
Lama Al-Qusairi, Denis Basquin, Ankita Roy, Renuga Devi Rajaram, Marc P Maillard, Arohan R Subramanya, Olivier Staub
Adaptation of the organism to potassium (K(+)) deficiency requires precise coordination among organs involved in K(+) homeostasis, including muscle, liver, and kidney. How the latter performs functional and molecular changes to ensure K(+) retention is not well understood. Here, we investigated the role of ubiquitin-protein ligase NEDD4-2, which negatively regulates the epithelial sodium channel (ENaC), Na(+)/Cl(-) cotransporter (NCC), and with no-lysine-kinase 1 (WNK1). After dietary K(+) restriction for 2 weeks, compared with control littermates, inducible renal tubular NEDD4-2 knockout (Nedd4L(Pax8/LC1) ) mice exhibited severe hypokalemia and urinary K(+) wasting...
March 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28289182/continuum-of-renin-independent-aldosteronism-in-normotension
#19
Rene Baudrand, Francisco J Guarda, Carlos Fardella, Gregory Hundemer, Jenifer Brown, Gordon Williams, Anand Vaidya
Primary aldosteronism is a severe form of autonomous aldosteronism. Milder forms of autonomous and renin-independent aldosteronism may be common, even in normotension. We characterized aldosterone secretion in 210 normotensives who had suppressed plasma renin activity (<1.0 ng/mL per hour), completed an oral sodium suppression test, received an infusion of angiotensin II, and had measurements of blood pressure and renal plasma flow. Continuous associations between urinary aldosterone excretion rate, renin, and potassium handling were investigated...
March 13, 2017: Hypertension
https://www.readbyqxmd.com/read/28288570/effect-of-tolvaptan-on-renal-water-and-sodium-excretion-and-blood-pressure-during-nitric-oxide-inhibition-a-dose-response-study-in-healthy-subjects
#20
Safa Al Therwani, Jeppe Bakkestrøm Rosenbæk, Frank Holden Mose, Jesper Nørgaard Bech, Erling Bjerregaard Pedersen
BACKGROUND: Tolvaptan is a selective vasopressin receptor antagonist. Nitric Oxide (NO) promotes renal water and sodium excretion, but the effect is unknown in the nephron's principal cells. In a dose-response study, we measured the effect of tolvaptan on renal handling of water and sodium and systemic hemodynamics, during baseline and NO-inhibition with L-NMMA (L-NG-monomethyl-arginine). METHODS: In a randomized, placebo-controlled, double blind, cross over study, 15 healthy subjects received tolvaptan 15, 30 and 45 mg or placebo...
March 13, 2017: BMC Nephrology
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