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https://www.readbyqxmd.com/read/28196131/altered-renal-sodium-handling-and-risk-of-incident-hypertension-results-of-the-olivetti-heart-study
#1
Lanfranco D'Elia, Francesco P Cappuccio, Roberto Iacone, Ornella Russo, Ferruccio Galletti, Pasquale Strazzullo
Renal tubular sodium (Na) handling plays a key role in blood pressure (BP) regulation. Several cross-sectional studies reported a positive association between higher proximal tubule fractional reabsorption of Na and BP, but no prospective investigation has been reported of this possible association. Hence, the purpose of this study was to estimate the predictive role of renal Na handling on the risk of incident hypertension and the changes in BP occurring in the 8-year follow-up observation of a sample of initially normotensive men (The Olivetti Heart Study)...
2017: PloS One
https://www.readbyqxmd.com/read/28190920/acute-alloxan-renal-toxicity-in-the-rat-initially-causes-degeneration-of-thick-ascending-limbs-of-henle
#2
Yui Terayama, Yasushi Kodama, Tetsuro Matsuura, Kiyokazu Ozaki
Alloxan (AL) is a material well-known to induce diabetes. Prior to inducing a prolonged diabetic state, AL causes acute tubulointerstitial nephritis. However, the precise primary target site and mechanism of its nephrotoxicity remain unclear. The objective of this study was to evaluate the morphological characteristics relevant to acute renal toxicity following AL administration. Rats were intravenously treated with AL. Eight hours after AL treatment, aquaporin 1-negative and Na/K pump-positive thick ascending limbs of Henle (TAL) were degenerated in the outer medulla...
January 2017: Journal of Toxicologic Pathology
https://www.readbyqxmd.com/read/28187982/the-renal-trpv4-channel-is-essential-for-adaptation-to-increased-dietary-potassium
#3
Mykola V Mamenko, Nabila Boukelmoune, Viktor N Tomilin, Oleg L Zaika, V Behrana Jensen, Roger G O'Neil, Oleh M Pochynyuk
To maintain potassium homeostasis, kidneys exert flow-dependent potassium secretion to facilitate kaliuresis in response to elevated dietary potassium intake. This process involves stimulation of calcium-activated large conductance maxi-K (BK) channels in the distal nephron, namely the connecting tubule and the collecting duct. Recent evidence suggests that the TRPV4 channel is a critical determinant of flow-dependent intracellular calcium elevations in these segments of the renal tubule. Here, we demonstrate that elevated dietary potassium intake (five percent potassium) increases renal TRPV4 mRNA and protein levels in an aldosterone-dependent manner and causes redistribution of the channel to the apical plasma membrane in native collecting duct cells...
February 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28179254/a-mathematical-model-of-the-rat-kidney-k-induced-natriuresis
#4
Alan M Weinstein
A model of the rat nephron (Am. J. Physiol. 308:F1098, 2015) has been extended with addition of medullary vasculature. Blood vessels contain solutes from the nephron model, plus additional species from the model of Atherton et al. (Am. J. Physiol. 247:F61, 1984), representing hemoglobin buffering. In contrast to prior models of the urine concentrating mechanism, reflection coefficients for DVR are near zero. Model unknowns are initial proximal tubule pressures and flows, connecting tubule pressure, and medullary interstitial pressures and concentrations...
February 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28174181/cardiovascular-benefits-associated-with-higher-dietary-k-versus-lower-dietary-na-evidence-from-population-and-mechanistic-studies
#5
Alicia A McDonough, Luciana C Veiras, Claire A Guevara, Donna L Ralph
The WHO ranks hypertension the leading global risk factor for disease, specifically, cardiovascular disease. Blood pressure is higher in westernized populations consuming sodium-rich processed foods compared to isolated societies consuming potassium-rich natural foods. Evidence suggests that lowering dietary Na(+) is particularly beneficial in hypertensives who consume a high Na(+) diet. Nonetheless, numerous population studies demonstrate a relationship between higher dietary K(+), estimated from urinary excretion or dietary recall, and lower blood pressure regardless of sodium intake...
February 7, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28148531/primary-proximal-tubule-hyperreabsorption-and-impaired-tubular-transport-counterregulation-determine-glomerular-hyperfiltration-in-diabetes-a-modeling-analysis
#6
Karen Melissa Hallow, Yeshitila Gebremichael, Gabriel Helmlinger, Volker Vallon
Glomerular hypertension and hyperfiltration in early diabetes is 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...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28133684/antioxidant-effect-of-vitamin-e-and-5-aminosalicylic-acid-on-acrylamide-induced-kidney-injury-in-rats
#7
Nisreen A Rajeh, Najlaa M Al-Dhaheri
To explore renal toxicity caused by sub-acute exposure of acrylamide and to study the protective effect of 5-Aminosalicylic acid (5-ASA) and Vitamin E (vit-E)on Acrylamide (ACR) induced renal toxicity. Methods: This study was conducted at King Fahad Medical Research Centre, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, between August and November 2015. A total of 49 adult Wistar rats (250 ± 20g) aged 60 days were kept in a controlled environment and used in the present study. The rats were divided into 7 groups (control, ACR alone, ACR+5-ASA, ACR+vit-E, ACR+ASA+vit-E, vit-E alone, and ASA alone)...
February 2017: Saudi Medical Journal
https://www.readbyqxmd.com/read/28125972/gitelman-syndrome-in-a-south-african-family-presenting-with-hypokalaemia-and-unusual-food-cravings
#8
Pieter Du Toit van der Merwe, Megan A Rensburg, William L Haylett, Soraya Bardien, M Razeen Davids
BACKGROUND: Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder characterised by renal salt wasting with hypokalaemia, metabolic alkalosis, hypomagnesaemia and hypocalciuria. It is caused by mutations in SLC12A3 encoding the sodium-chloride cotransporter on the apical membrane of the distal convoluted tubule. We report a South African family with five affected individuals presenting with hypokalaemia and unusual food cravings. METHODS: The affected individuals and two unaffected first degree relatives were enrolled into the study...
January 26, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28120456/endothelin-1-mediates-natriuresis-but-not-polyuria-during-vitamin-d-induced-acute-hypercalcemia
#9
Natsuko Tokonami, Lydie Cheval, Isabelle Monnay, Guillaume Meurice, Johaness Loffing, Eric Feraille, Pascal Houillier
Acute hypercalcemia increases urinary sodium and water excretion; however, the underlying molecular mechanism remains unclear. As vitamin D-induced hypercalcemia increases the renal expression of endothelin (ET)-1, we hypothesized that ET-1 mediates the effects of hypercalcemia on renal sodium and water handling. Hypercalcemia was induced in 8 week-old, PTH-supplemented, male mice by oral administration of dihydrotachysterol (DHT) for 3 days. DHT-treated mice became hypercalcemic and displayed increased urinary water and sodium excretion compared to controls...
January 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28100643/fluid-shear-stress-increases-transepithelial-transport-of-ca2-in-ciliated-distal-convoluted-and-connecting-tubule-cells
#10
Sami G Mohammed, Francisco J Arjona, Femke Latta, René J M Bindels, Ronald Roepman, Joost G J Hoenderop
In kidney, transcellular transport of Ca(2+) is mediated by transient receptor potential vanilloid 5 and Na(+)-Ca(2+) exchanger 1 proteins in distal convoluted and connecting tubules (DCT and CNT, respectively). It is not yet understood how DCT/CNT cells can adapt to differences in tubular flow rate and, consequently, Ca(2+) load. This study aims to elucidate the molecular mechanisms by which DCT/CNT cells sense fluid dynamics to control transepithelial Ca(2+) reabsorption and whether their primary cilia play an active role in this process...
January 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28096417/phosphorylation-by-pkc-and-pka-regulate-the-kinase-activity-and-downstream-signaling-of-wnk4
#11
Maria Castañeda-Bueno, Juan Pablo Arroyo, Junhui Zhang, Jeremy Puthumana, Orlando Yarborough, Shigeru Shibata, Lorena Rojas-Vega, Gerardo Gamba, Jesse Rinehart, Richard P Lifton
With-no-lysine kinase 4 (WNK4) regulates electrolyte homeostasis and blood pressure. WNK4 phosphorylates the kinases SPAK (Ste20-related proline alanine-rich kinase) and OSR1 (oxidative stress responsive kinase), which then phosphorylate and activate the renal Na-Cl cotransporter (NCC). WNK4 levels are regulated by binding to Kelch-like 3, targeting WNK4 for ubiquitylation and degradation. Phosphorylation of Kelch-like 3 by PKC or PKA downstream of AngII or vasopressin signaling, respectively, abrogates binding...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28074976/utility-of-urinary-markers-in-the-assessment-of-renal-dysfunction-in-canine-babesiosis
#12
Dagmara Winiarczyk, Łukasz Adaszek, Michał Bartnicki, Beata Abramowicz, Paweł Łyp, Jacek Madany, Stanisław Winiarczyk
OBJECTIVE: Canine babesiosis is a common and clinically significant tick-borne disease caused by haemoprotozoan parasites of the genus Babesia. Acute renal failure is considered to be one of the most prevalent complications of canine babesiosis. This complication leads to a decrease in the glomerular filtration rate and in consequence causes azotemia and uremia. The objective of this study was to assess the localization and extent of renal damage in dogs infected with Babesia canis using an urinary marker for glomerular (urinary immunoglobulin G, uIgG), proximal tubular dysfunction (urinary retinol binding protein, uRBP) and distal tubular dysfunction (urinary Tamm-Horsfal protein, uTHP)...
January 11, 2017: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
https://www.readbyqxmd.com/read/28067240/cd8-t-cells-stimulate-na-cl-co-transporter-ncc-in-distal-convoluted-tubules-leading-to-salt-sensitive-hypertension
#13
Yunmeng Liu, Tonya M Rafferty, Sung W Rhee, Jessica S Webber, Li Song, Benjamin Ko, Robert S Hoover, Beixiang He, Shengyu Mu
Recent studies suggest a role for T lymphocytes in hypertension. However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown. Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals. In particular, CD8(+) T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8(+) T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28064277/smad2-phosphorylation-in-diabetic-kidney-tubule-epithelial-cells-is-associated-with-modulation-of-several-transforming-growth-factor-%C3%AE-family-members
#14
Lise Høj Thomsen, Morten Fog-Tonnesen, Lisbeth Nielsen Fink, Jenny Norlin, Amaya García de Vinuesa, Troels Krarup Hansen, Emile de Heer, Peter Ten Dijke, Alexander Rosendahl
BACKGROUND: The role of transforming growth factor-β (TGF-β) has recently gained much attention in diabetic nephropathy and kidney fibrosis. In this study, we extend this to an assessment of transcriptional regulation of the entire TGF-β superfamily in kidneys from diabetic vs. healthy mice. In order to study the translation between mouse model and patients, we evaluated the signature of phosphorylated Sma- and Mad-related protein 2 (pSmad2), as molecular marker of TGF-β/activin activity, in the kidneys of streptozotocin (STZ)-treated mice compared to that of type 1 diabetes (T1D) patients...
January 7, 2017: Nephron
https://www.readbyqxmd.com/read/28064162/acute-genetic-ablation-of-pendrin-lowers-blood-pressure-in-mice
#15
Francesco Trepiccione, Christelle Soukaseum, Veronique Baudrie, Yusuke Kumai, Jacques Teulon, Bruno Villoutreix, Nicolas Cornière, Philine Wangemann, Andrew J Griffith, Yoon Byung Choi, Juliette Hadchouel, Regine Chambrey, Dominique Eladari
BACKGROUND: Pendrin, the chloride/bicarbonate exchanger of β-intercalated cells of the renal connecting tubule and the collecting duct, plays a key role in NaCl reabsorption by the distal nephron. Therefore, pendrin may be important for the control of extracellular fluid volume and blood pressure. METHODS: Here, we have used a genetic mouse model in which the expression of pendrin can be switched-on in vivo by the administration of doxycycline. Pendrin can also be rapidly removed when doxycycline administration is discontinued...
January 7, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28052988/potassium-sensing-by-renal-distal-tubules-requires-kir4-1
#16
Catherina A Cuevas, Xiao-Tong Su, Ming-Xiao Wang, Andrew S Terker, Dao-Hong Lin, James A McCormick, Chao-Ling Yang, David H Ellison, Wen-Hui Wang
The mammalian distal convoluted tubule (DCT) makes an important contribution to potassium homeostasis by modulating NaCl transport. The thiazide-sensitive Na(+)/Cl(-) cotransporter (NCC) is activated by low potassium intake and by hypokalemia. Coupled with suppression of aldosterone secretion, activation of NCC helps to retain potassium by increasing electroneutral NaCl reabsorption, therefore reducing Na(+)/K(+) exchange. Yet the mechanisms by which DCT cells sense plasma potassium concentration and transmit the information to the apical membrane are not clear...
January 4, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28033128/renal-function-of-cyclin-m2-mg2-transporter-maintains-blood-pressure
#17
Yosuke Funato, Daisuke Yamazaki, Hiroaki Miki
OBJECTIVES: Epidemiological studies have shown that magnesium intake/excretion is inversely correlated with blood pressure (BP), and artificial supplementation of magnesium was able to prevent hypertension. However, there has been no molecular genetic study showing the importance of magnesium homeostasis in BP regulation. METHODS: We analyzed magnesium content and BP of mice lacking genes encoding cyclin M (CNNM) Mg transporter family proteins. RESULTS: Systemic heterozygotes and the kidney-specific homozygotes for Cnnm2-deficient alleles are both viable and show hypomagnesemia, indicating the important function of CNNM2 in maintaining magnesium homeostasis in the kidney...
March 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28003191/calcineurin-inhibitor-cyclosporine-a-activates-renal-na-k-cl-cotransporters-via-local-and-systemic-mechanisms
#18
Katharina Ilse Blankenstein, Aljona Borschewski, Robert Labes, Alexander Paliege, Christin Boldt, James A McCormick, David H Ellison, Michael Bader, Sebastian Bachmann, Kerim Mutig
Calcineurin dephosphorylates NFAT transcription factors, thereby facilitating T-cell mediated immune responses. Calcineurin inhibitors are instrumental for immunosuppression after organ transplantation, but may cause side effects including hypertension and electrolyte disorders. Kidneys were recently shown to display activation of the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA)...
December 21, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28003188/insulin-like-growth-factor-binding-protein-7-and-tissue-inhibitor-of-metalloproteinases-2-differential-expression-and-secretion-in-human-kidney-tubule-cells
#19
David R Emlet, Nuria Pastor-Soler, Allison Marciszyn, Xiaoyan Wen, Hernando Gomez, William H Humphries, Seth Morrisroe, Jacob K Volpe, John A Kellum
We have characterized the expression and secretion of the acute kidney injury (AKI) biomarkers insulin-like growth factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in human kidney epithelial cells in primary cell culture and tissue. We established cell culture model systems of primary kidney cells of proximal and distal tubule origin and observed that both proteins are indeed expressed and secreted in both tubule cell types in vitro. However, TIMP-2 is both expressed and secreted preferentially by cells of distal tubule origin, while IGFBP7 is equally expressed across tubule cell types yet preferentially secreted by cells of proximal tubule origin...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27999878/in-vivo-imaging-of-systemic-transport-and-elimination-of-xenobiotics-and-endogenous-molecules-in-mice
#20
Raymond Reif, Ahmed Ghallab, Lynette Beattie, Georgia Günther, Lars Kuepfer, Paul M Kaye, Jan G Hengstler
We describe a two-photon microscopy-based method to evaluate the in vivo systemic transport of compounds. This method comprises imaging of the intact liver, kidney and intestine, the main organs responsible for uptake and elimination of xenobiotics and endogenous molecules. The image quality of the acquired movies was sufficient to distinguish subcellular structures like organelles and vesicles. Quantification of the movement of fluorescent dextran and fluorescent cholic acid derivatives in different organs and their sub-compartments over time revealed significant dynamic differences...
December 20, 2016: Archives of Toxicology
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