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salt and progression of renal disease

Kensei Taguchi, Sho-Ichi Yamagishi, Miyuki Yokoro, Sakuya Ito, Goh Kodama, Yusuke Kaida, Yosuke Nakayama, Ryotaro Ando, Nana Yamada-Obara, Katsuhiko Asanuma, Takanori Matsui, Yuichiro Higashimoto, Craig R Brooks, Seiji Ueda, Seiya Okuda, Kei Fukami
The mineralocorticoid receptor (MR) and its downstream signaling play an important role in hypertensive renal injury. The interaction of advanced glycation end products (AGE) with their receptor (RAGE) is involved in the progression of renal disease. However, the pathological crosstalk between AGE-RAGE axis and MR system in kidney derangement remains unclear. We screened DNA-aptamer directed against RAGE (RAGE-apt) in vitro and examined its effects on renal injury in uninephrectomized deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mice...
February 8, 2018: Scientific Reports
Aziz Zaanan, Emmanuelle Samalin, Thomas Aparicio, Olivier Bouche, Pierre Laurent-Puig, Sylvain Manfredi, Pierre Michel, Carole Monterymard, Marie Moreau, Philippe Rougier, David Tougeron, Julien Taieb, Christophe Louvet
INTRODUCTION: In advanced gastric cancer, doublet regimen including platinum salts and fluoropyrimidine is considered as a standard first-line treatment. The addition of docetaxel (75 mg/m2  q3w) to cisplatin (75 mg/m2  q3w) and 5-fluorouracil has been shown to improve efficacy. However, this regimen (DCF) was associated with frequent severe toxicities (including more complicated neutropenia), limiting its use in clinical practice. Interesting alternative docetaxel-based regimens have been developed that need to be validated...
February 3, 2018: Digestive and Liver Disease
Yan Liu, David Goldfarb, Tarek M El-Achkar, John C Lieske, Xue-Ru Wu
Expression of Tamm-Horsfall protein (THP or uromodulin) is highly restricted to the kidneys' thick ascending limb (TAL) of loop of Henle. Despite the unique location and recent association of THP gene mutations with hereditary uromodulin-associated kidney disease and THP single nucleotide polymorphisms with chronic kidney disease and hypertension, the physiological function(s) of THP and its pathological involvement remain incompletely understood. By studying age-dependent changes of THP knockout (KO) mice, we show here that young KO mice had significant salt and water wasting but were partially responsive to furosemide, due to decreased luminal translocation of Na-K-Cl cotransporter 2 (NKCC2) in the TAL...
January 10, 2018: American Journal of Physiology. Renal Physiology
Luca Visconti, Valeria Cernaro, Sebastiano Calimeri, Antonio Lacquaniti, Francesca De Gregorio, Carlo Alberto Ricciardi, Viviana Lacava, Domenico Santoro, Michele Buemi
The impact of water intake has been studied in several renal diseases. For example, increasing water intake is useful to prevent primary and secondary nephrolithiasis. In autosomal dominant polycystic kidney disease, arginine vasopressin (AVP) is involved in the progression of the disease, and water intake could play a therapeutic role by inhibiting the synthesis of AVP, but its efficacy is still controversial. Conversely, the use of aquaretics, which are antagonists of AVP V2 receptors, results in the reduction of the increase rate of total kidney volume with a slower decline of glomerular filtration rate...
November 14, 2017: Journal of Renal Nutrition
Satoshi Washino, Keiko Hosohata, Denan Jin, Shinji Takai, Tomoaki Miyagawa
Dietary sodium intake has been associated with progression to chronic kidney disease (CKD) as well as hypertension. A high-salt intake causes renal damage independent of hypertension. Because traditional renal biomarkers are insensitive, it is difficult to detect renal injury induced by a high-salt intake, especially in normotensive patients. Here, we investigated whether newly developed renal biomarkers could be detected earlier than traditional biomarkers under a high-salt intake, in normotensive rats. Male Wistar Kyoto rats (WKY) received a regular (0...
October 12, 2017: Clinical and Experimental Pharmacology & Physiology
Keiko Hosohata
High salt intake has been related to the development to chronic kidney disease (CKD) as well as hypertension. In its early stages, symptoms of CKD are usually not apparent, especially those that are induced in a "silent" manner in normotensive individuals, thereby providing a need for some kind of urinary biomarker to detect injury at an early stage. Because traditional renal biomarkers such as serum creatinine are insensitive, it is difficult to detect kidney injury induced by a high-salt diet, especially in normotensive individuals...
September 30, 2017: International Journal of Molecular Sciences
Silas Culver, Caixia Li, Helmy M Siragy
PURPOSE OF REVIEW: The intrarenal renin-angiotensin-aldosterone system (RAS) is an independent paracrine hormonal system with an increasingly prominent role in hypertension and renal disease. Two enzyme components of this system are angiotensin-converting enzyme (ACE) and more recently discovered ACE2. The purpose of this review is to describe recent discoveries regarding the roles of intrarenal ACE and ACE2 and their interaction. RECENT FINDINGS: Renal tubular ACE contributes to salt-sensitive hypertension...
September 19, 2017: Current Hypertension Reports
Tsubasa Yokota, Kohei Omachi, Mary Ann Suico, Haruka Kojima, Misato Kamura, Keisuke Teramoto, Shota Kaseda, Jun Kuwazuru, Tsuyoshi Shuto, Hirofumi Kai
A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown...
2017: PloS One
Tanya L Henshall, Jantina A Manning, Omri S Alfassy, Pranay Goel, Natasha A Boase, Hiroshi Kawabe, Sharad Kumar
NEDD4-2 (NEDD4L), a ubiquitin protein ligase of the Nedd4 family, is a key regulator of cell surface expression and activity of the amiloride-sensitive epithelial Na+ channel (ENaC). While hypomorphic alleles of Nedd4-2 in mice show salt-sensitive hypertension, complete knockout results in pulmonary distress and perinatal lethality due to increased cell surface levels of ENaC. We now show that Nedd4-2 deficiency in mice also results in an unexpected progressive kidney injury phenotype associated with elevated ENaC and Na+ Cl- cotransporter expression, increased Na+ reabsorption, hypertension and markedly reduced levels of aldosterone...
December 2017: Cell Death and Differentiation
Antonio De Pascalis, Alessandro Balducci
The progression of chronic kidney disease CKD is largely independent of the underlying kidney disorder once renal function has fallen below a critical level. Hypertension is an independent risk factor for disease progression in both adult and pediatric patients with kidney disorders. Optimal blood pressure control (130 /80mm Hg) represents a main goal of conservative therapy in patients with chronic kidney disease CKD but it is rarely achieved in clinical practice. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are more effective than other drugs in slowing progression of proteinuric CKD...
March 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
Per Svenningsen, Gitte Rye Hinrichs, Rikke Zachar, Rikke Ydegaard, Boye L Jensen
The plasminogen system is important for fibrinolysis in addition to tissue remodeling and inflammation with significance for kidney disease. The system consists of the circulating zymogen plasminogen (Plg) and the tissue- and urokinase-type plasminogen activators, tPA and uPA, expressed in the glomeruli, endothelium and tubular epithelium, respectively, and the inhibitors α2-antiplasmin and plasminogen activator inhibitor-type1, PAI-1. Plasminogen is activated by surface receptors, some with renal expression: urokinase-type plasminogen activator receptor (uPAR), plasminogen receptor KT (Plg-RKT), and tPA, most evident in the endothelium...
June 27, 2017: Pflügers Archiv: European Journal of Physiology
Sebastian Bachmann, Kerim Mutig
Vasopressin (AVP) induces antidiuresis, thus playing an essential role in body water and electrolyte homeostasis. Its antidiuretic effects are mediated chiefly by V2 vasopressin receptors (V2R) expressed along the distal nephron and collecting duct epithelia. NaCl reabsorption in the distal nephron, which includes the thick ascending limb (TAL) and distal convoluted tubule (DCT), largely depends on the activity of two structurally related Na-(K)-Cl cotransporters, NKCC2 in TAL and NCC in DCT. AVP-induced activation of these transporters contributes to urine concentration and renal electrolyte reabsorption...
August 2017: Pflügers Archiv: European Journal of Physiology
Yohei Tanada, Junji Okuda, Takao Kato, Eri Minamino-Muta, Ichijiro Murata, Tomoyoshi Soga, Tetsuo Shioi, Takeshi Kimura
BACKGROUND: The kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension. METHODS: We used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney...
2017: PeerJ
Michiel F Schreuder
Life with a solitary functioning kidney (SFK) may be different from that when born with two kidneys. Based on the hyperfiltration hypothesis, a SFK may lead to glomerular damage with hypertension, albuminuria and progression towards end-stage renal disease. As the prognosis of kidney donors was considered to be very good, having a SFK has been considered to be a benign condition. In contrast, our research group has demonstrated that being born with or acquiring a SFK in childhood results in renal injury before adulthood in over 50% of those affected...
May 29, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Lanying Li, Jiawen Li, Lishan Tan, Minzi Qiu, Mengbi Zhang, Aiqing Li
Hypothalamic paraventricular nucleus (PVN) is a cardiovascular regulating center within the brain, which plays a critical role in high salt-induced progression of chronic renal failure (CRF). However, the phosphoproteomic changes in the PVN caused by CRF remain unclear. This study aimed to perform large-scale phosphoproteomic analysis of PVN induced by CRF and high salt intake. In this study, eight weeks post 5/6 nephrectomy (CRF model) or sham operation, Sprague-Dawley rats were fed a high-salt (4%) or normal-salt (0...
May 24, 2017: Brain Research
Jesus Egido, Jorge Rojas-Rivera, Sebastian Mas, Marta Ruiz-Ortega, Ana Belen Sanz, Emilio Gonzalez Parra, Carmen Gomez-Guerrero
Endothelin-1 (ET-1) is the most potent vasoconstrictor, and is involved in the renal regulation of salt and water homeostasis. When produced in excess in the kidney, ET-1 promotes proteinuria and tubulointerstitial injury. There is great interest in the clinical use of endothelin receptor antagonists (ERAs) in chronic kidney disease (CKD), mainly in diabetic nephropathy (DN). Areas covered: Physiopathological actions of ET-1 on the kidney. Both dual ETAR/ETBR (bosentan) or ETAR specific endothelin antagonists (avosentan and atrasentan, among others), which have progressed to early clinical development, with particular emphasis on atrasentan...
June 2017: Expert Opinion on Investigational Drugs
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...
July 2017: Kidney International
Bradley T Endres, Ruben M Sandoval, George J Rhodes, Silvia B Campos-Bilderback, Malgorzata M Kamocka, Christopher McDermott-Roe, Alexander Staruschenko, Bruce A Molitoris, Aron M Geurts, Oleg Palygin
Hypertension is one of the most prevalent diseases worldwide and a major risk factor for renal failure and cardiovascular disease. The role of albuminuria, a common feature of hypertension and robust predictor of cardiorenal disorders, remains incompletely understood. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a rat model of hypertension, the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two-photon-based imaging to investigate the complex renal physiological changes that occur during salt-induced hypertension...
August 1, 2017: American Journal of Physiology. Renal Physiology
Waleska C Dornas, Leonardo M Cardoso, Maísa Silva, Natália L S Machado, Deoclécio A Chianca-Jr, Andréia C Alzamora, Wanderson G Lima, Vincent Lagente, Marcelo E Silva
There is evidence that diets rich in salt or simple sugars as fructose are associated with abnormalities in blood pressure regulation. However, the mechanisms underlying pathogenesis of salt- and fructose-induced kidney damage and/or consequent hypertension yet remain largely unexplored. Here, we tested the role of oxidative state as an essential factor along with high salt and fructose treatment in causing hypertension. Fischer male rats were supplemented with a high-fructose diet (20% in water) for 20 weeks and maintained on high-salt diet (8%) associate in the last 10 weeks...
April 11, 2017: Scientific Reports
Ramalingam Sharmila, Ganapathy Sindhu
BACKGROUND: Plant sterols are the major source of micronutrients and have not shown any obvious side effects in human. β-sitosterol is one of the most prevalent phytosterols which have been recorded in ancient medicinal history for its use in the treatment of many chronic diseases, especially cancer. The modulations of mitogen-activated protein kinases' (MAPKs') play a crucial role in the development of human renal cell carcinoma. OBJECTIVE: The aim of the current study is to evaluate the antigenotoxic and anticancer role of β-sitosterol against renal carcinogen...
January 2017: Pharmacognosy Magazine
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