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Tubule glomerular feedback

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https://www.readbyqxmd.com/read/28582367/do-effects-of-sodium-glucose-cotransporter-2-inhibitors-in-patients-with-diabetes-give-insight-into-potential-use-in-non-diabetic-kidney-disease
#1
Harindra Rajasekeran, David Z Cherney, Julie A Lovshin
PURPOSE OF REVIEW: Our aim was to review the rationale for the role of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) as renoprotective therapy in patients with and without diabetes. RECENT FINDINGS: SGLT-2i are antihyperglycemic agents, approved for treating type 2 diabetes to reduce glycosylated hemoglobin, type A1c. Primary glucoregulatory effects occur through selective inhibition of SGLT-2 at the renal proximal tubule promoting glucosuria leading to blood glucose lowering...
June 2, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28424211/connecting-tubule-glomerular-feedback-mediates-tubuloglomerular-feedback-resetting-post-unilateral-nephrectomy
#2
Sumit R Monu, Yilin Ren, J X Masjoan Juncos, Kristopher Kutskill, Hong Wang, Nitin Kumar, Edward L Peterson, Oscar A Carretero
Unilaterally nephrectomized rats (UNx) have higher glomerular capillary pressure (PGC) that can cause significant glomerular injury in the remnant kidney. PGC is controlled by the ratio of afferent (Af-Art) and efferent arteriole resistance. Af-Art resistance in turn is regulated by two intrinsic feedback mechanisms: 1) Tubuloglomerular feedback (TGF) that causes Af-Art constriction in response to increased NaCl in the macula densa and 2) connecting tubule glomerular feedback (CTGF) that causes Af-Art dilatation in response to an increase in NaCl transport in the connecting tubule via the epithelial sodium channel (ENaC)...
April 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28299616/promise-of-sglt2-inhibitors-in-heart-failure-diabetes-and-beyond
#3
REVIEW
Pieter Martens, Chantal Mathieu, Frederik H Verbrugge
This review provides mechanistic insight in the pleiotropic effects of sodium-glucose transporter-2 (SGLT-2) inhibitors with particular interest to the pathophysiology of heart failure. The SGLT-2 inhibitor empagliflozin has recently demonstrated an unprecedented 38% reduction in cardiovascular mortality in patients with diabetes. Despite modest effects on long-term glycemic control, highly significant reductions in heart failure admissions and end-stage kidney disease were observed. SGLT-2 inhibitors are the latest approved class of glucose-lowering agents...
March 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28298361/intrarenal-signaling-mediated-by-cck-plays-a-role-in-salt-intake-induced-natriuresis
#4
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/28228405/inhibition-of-romk-blocks-macula-densa-tubuloglomerular-feedback-yet-causes-renal-vasoconstriction-in-anesthetized-rats
#5
Magali Araujo, William J Welch, Xiaoyan Zhou, Kathleen Sullivan, Shawn Walsh, Alexander Pasternak, Christopher S Wilcox
The Na+/K+/2Cl- cotransporter (NKCC2) on the loop of Henle is the site of action of furosemide. Since outer medullary potassium channel (ROMK) inhibitors prevent reabsorption by NKCC2, we tested the hypothesis that ROMK inhibition with a novel, selective ROMK inhibitor (Compound C) blocks tubuloglomerular feedback (TGF) and reduces vascular resistance. Loop perfusion of either ROMK inhibitor or furosemide caused dose-dependent blunting of TGF, but the response to furosemide was 10-fold more sensitive (IC50= 10-6M for furosemide and IC50=10-5M for Compound C)...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28148531/primary-proximal-tubule-hyperreabsorption-and-impaired-tubular-transport-counterregulation-determine-glomerular-hyperfiltration-in-diabetes-a-modeling-analysis
#6
K Melissa Hallow, Yeshitila Gebremichael, Gabriel Helmlinger, Volker Vallon
Glomerular hypertension and hyperfiltration in early diabetes are associated with development and progression of diabetic kidney disease. The tubular hypothesis of diabetic hyperfiltration proposes that it is initiated by a primary increase in sodium (Na) reabsorption in the proximal tubule (PT) and the resulting tubuloglomerular feedback (TGF) response and lowering of Bowman space pressure (PBow). Here we utilized a mathematical model of the human kidney to investigate over acute and chronic timescales the mechanisms responsible for the magnitude of the hyperfiltration response...
May 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27878313/targeting-renal-glucose-reabsorption-to-treat-hyperglycaemia-the-pleiotropic-effects-of-sglt2-inhibition
#7
REVIEW
Volker Vallon, Scott C Thomson
Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule...
February 2017: Diabetologia
https://www.readbyqxmd.com/read/27754097/os-21-02-connecting-tubule-glomerular-feedback-ctgf-in-renal-hemodynamics-and-blood-pressure-regulation-after-unilateral-nephrectomy-unx
#8
Cesar Romero, Sumit Monu, Glauber Cabral, Robert Knight, Oscar Carretero
OBJECTIVE: Renal hemodynamics is critical for regulation of glomerular filtration (GFR), sodium excretion and blood pressure (BP), and it depends on myogenic response, tubuloglomerular feedback (TGF) and connecting tubule-glomerular feedback (CTGF). CTGF dilates afferent arteriole in response to high sodium in connecting tubule (CNT), counteracting and resetting TGF; and increasing the plasma flow and glomerular pressure favoring sodium excretion. CTGF is initiated by epithelial sodium channel (ENaC) activation in CNT and inhibited by ENaC blocker Benzamil...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27643022/os-21-02-connecting-tubule-glomerular-feedback-ctgf-in-renal-hemodynamics-and-blood-pressure-regulation-after-unilateral-nephrectomy-unx
#9
Cesar Romero, Sumit Monu, Glauber Cabral, Robert Knight, Oscar Carretero
OBJECTIVE: Renal hemodynamics is critical for regulation of glomerular filtration (GFR), sodium excretion and blood pressure (BP), and it depends on myogenic response, tubuloglomerular feedback (TGF) and connecting tubule-glomerular feedback (CTGF). CTGF dilates afferent arteriole in response to high sodium in connecting tubule (CNT), counteracting and resetting TGF; and increasing the plasma flow and glomerular pressure favoring sodium excretion. CTGF is initiated by epithelial sodium channel (ENaC) activation in CNT and inhibited by ENaC blocker Benzamil...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27413197/mechanisms-of-connecting-tubule-glomerular-feedback-enhancement-by-aldosterone
#10
YiLin Ren, Branislava Janic, Kristopher Kutskill, Edward L Peterson, Oscar A Carretero
Connecting tubule glomerular feedback (CTGF) is a mechanism where an increase in sodium (Na) concentration in the connecting tubule (CNT) causes the afferent arteriole (Af-Art) to dilate. We recently reported that aldosterone within the CNT lumen enhances CTGF via a nongenomic effect involving GPR30 receptors and sodium/hydrogen exchanger (NHE), but the signaling pathways of this mechanism are unknown. We hypothesize that aldosterone enhances CTGF via cAMP/protein kinase A (PKA) pathway that activates protein kinase C (PKC) and stimulates superoxide (O2(-)) production...
December 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27225921/-mechanisms-of-caffeine-induced-diuresis
#11
Barbara Marx, Éléonore Scuvée, Jacqueline Scuvée-Moreau, Vincent Seutin, François Jouret
Caffeine is an alkaloid which belongs to the family of methylxanthines and is present in beverages, food and drugs. Caffeine competitively antagonizes the adenosine receptors (AR), which are G protein-coupled receptors largely distributed throughout the body, including brain, heart, vessels and kidneys. Caffeine consumption has a well-known diuretic effect. The homeostasis of salt and water involves different segments of the nephron, in which adenosine plays complex roles depending on the differential expression of AR...
May 2016: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/27023838/kidney-tubules-intertubular-vascular-and-glomerular-cross-talk
#12
REVIEW
David A Ferenbach, Joseph V Bonventre
PURPOSE OF REVIEW: The kidney mediates the excretion or conservation of water and electrolytes in the face of changing fluid and salt intake and losses. To ultrafilter and reabsorb the exact quantities of free water and salts to maintain euvolemia a range of endocrine, paracrine, and hormonal signaling systems have evolved linking the tubules, capillaries, glomeruli, arterioles, and other intrinsic cells of the kidney. Our understanding of these systems remains incomplete. RECENT FINDINGS: Recent work has provided new insights into the workings of the communication pathways between tubular segments and the glomeruli and vasculature, with novel therapeutic agents in development...
May 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/26972744/modeling-the-effects-of-positive-and-negative-feedback-in-kidney-blood-flow-control
#13
Runjing Liu, Anita T Layton
Blood flow in the mammalian kidney is tightly autoregulated. One of the important autoregulation mechanisms is the myogenic response, which is activated by perturbations in blood pressure along the afferent arteriole. Another is the tubuloglomerular feedback, which is a negative feedback that responds to variations in tubular fluid [Cl(-)] at the macula densa.(1) When initiated, both the myogenic response and the tubuloglomerular feedback adjust the afferent arteriole muscle tone. A third mechanism is the connecting tubule glomerular feedback, which is a positive feedback mechanism located at the connecting tubule, downstream of the macula densa...
June 2016: Mathematical Biosciences
https://www.readbyqxmd.com/read/26574046/acetazolamide-attenuates-lithium-induced-nephrogenic-diabetes-insipidus
#14
COMPARATIVE STUDY
Theun de Groot, Anne P Sinke, Marleen L A Kortenoeven, Mohammad Alsady, Ruben Baumgarten, Olivier Devuyst, Johannes Loffing, Jack F Wetzels, Peter M T Deen
To reduce lithium-induced nephrogenic diabetes insipidus (lithium-NDI), patients with bipolar disorder are treated with thiazide and amiloride, which are thought to induce antidiuresis by a compensatory increase in prourine uptake in proximal tubules. However, thiazides induced antidiuresis and alkalinized the urine in lithium-NDI mice lacking the sodium-chloride cotransporter, suggesting that inhibition of carbonic anhydrases (CAs) confers the beneficial thiazide effect. Therefore, we tested the effect of the CA-specific blocker acetazolamide in lithium-NDI...
July 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/26367377/effect-of-acetazolamide-on-obesity-induced-glomerular-hyperfiltration-a-randomized-controlled-trial
#15
RANDOMIZED CONTROLLED TRIAL
Boris Zingerman, Michal Herman-Edelstein, Arie Erman, Sarit Bar Sheshet Itach, Yaacov Ori, Benaya Rozen-Zvi, Uzi Gafter, Avry Chagnac
AIMS: Obesity is an important risk factor for the development of chronic kidney disease. One of the major factors involved in the pathogenesis of obesity-associated kidney disease is glomerular hyperfiltration. Increasing salt-delivery to the macula densa is expected to decrease glomerular filtration rate (GFR) by activating tubuloglomerular feedback. Acetazolamide, a carbonic anhydrase inhibitor which inhibits salt reabsorption in the proximal tubule, increases distal salt delivery. Its effects on obesity-related glomerular hyperfiltration have not previously been studied...
2015: PloS One
https://www.readbyqxmd.com/read/25834230/renal-autoregulation-in-health-and-disease
#16
REVIEW
Mattias Carlström, Christopher S Wilcox, William J Arendshorst
Intrarenal autoregulatory mechanisms maintain renal blood flow (RBF) and glomerular filtration rate (GFR) independent of renal perfusion pressure (RPP) over a defined range (80-180 mmHg). Such autoregulation is mediated largely by the myogenic and the macula densa-tubuloglomerular feedback (MD-TGF) responses that regulate preglomerular vasomotor tone primarily of the afferent arteriole. Differences in response times allow separation of these mechanisms in the time and frequency domains. Mechanotransduction initiating the myogenic response requires a sensing mechanism activated by stretch of vascular smooth muscle cells (VSMCs) and coupled to intracellular signaling pathways eliciting plasma membrane depolarization and a rise in cytosolic free calcium concentration ([Ca(2+)]i)...
April 2015: Physiological Reviews
https://www.readbyqxmd.com/read/25807826/-nucleotide-receptors-and-renal-function
#17
REVIEW
Maciej Jankowski
Kidney plays a key role in homeostasis of human body. It has heterogenic structure and is characterized by complicated vascular beds and numbers of sympathetic nerves endings. Nucleotides receptors are involved in the regulation of blood flow, a fundamental process for renal function. Plasma is filtrated in renal glomerulus and activity of nucleotides receptors located on cells of glomerular filter modifies the physi- cochemical properties of filter and affects the filtration process. Electrolytes, water and low molecular weight molecules are reabsorbed from tubular fluid or secreted into fluid in proximal and distal tubules...
2014: Postepy Biochemii
https://www.readbyqxmd.com/read/25715987/tubuloglomerular-and-connecting-tubuloglomerular-feedback-during-inhibition-of-various-na-transporters-in-the-nephron
#18
Hong Wang, Martin A D'Ambrosio, YiLin Ren, Sumit R Monu, Pablo Leung, Kristopher Kutskill, Jeffrey L Garvin, Branislava Janic, Edward L Peterson, Oscar A Carretero
Afferent (Af-Art) and efferent arterioles resistance regulate glomerular capillary pressure. The nephron regulates Af-Art resistance via: 1) vasoconstrictor tubuloglomerular feedback (TGF), initiated in the macula densa via Na-K-2Cl cotransporters (NKCC2) and 2) vasodilator connecting tubuloglomerular feedback (CTGF), initiated in connecting tubules via epithelial Na channels (ENaC). Furosemide inhibits NKCC2 and TGF. Benzamil inhibits ENaC and CTGF. In vitro, CTGF dilates preconstricted Af-Arts. In vivo, benzamil decreases stop-flow pressure (PSF), suggesting that CTGF antagonizes TGF; however, even when TGF is blocked, CTGF does not increase PSF, suggesting there is another mechanism antagonizing CTGF...
May 1, 2015: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/25694480/a-mathematical-model-of-the-rat-nephron-glucose-transport
#19
Alan M Weinstein
Mathematical models of the proximal tubule (PT), loop of Henle (LOH), and distal nephron have been combined to simulate transport by rat renal tubules. The ensemble is composed of 24,000 superficial (SF) nephrons and 12,000 juxtamedullary (JM) nephrons in 5 classes (according to LOH length); all coalesce into 7,200 connecting tubules (CNT). Medullary interstitial solute concentrations are specified. The model equations require that each nephron glomerular filtration rate (GFR) satisfies a tubuloglomerular feedback (TGF) relationship, and each initial hydrostatic pressure yields a common CNT pressure; that common CNT pressure is determined from an overall distal hydraulic resistance to flow...
May 15, 2015: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/25694479/a-mathematical-model-of-rat-proximal-tubule-and-loop-of-henle
#20
Alan M Weinstein
Proximal tubule and loop of Henle function are coupled, with proximal transport determining loop fluid composition, and loop transport modulating glomerular filtration via tubuloglomerular feedback (TGF). To examine this interaction, we begin with published models of the superficial rat proximal convoluted tubule (PCT; including flow-dependent transport in a compliant tubule), and the rat thick ascending Henle limb (AHL). Transport parameters for this PCT are scaled down to represent the proximal straight tubule (PST), which is connected to the thick AHL via a short descending limb...
May 15, 2015: American Journal of Physiology. Renal Physiology
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