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water and progression of renal disease

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https://www.readbyqxmd.com/read/28644734/high-throughput-phenotypic-screening-of-kinase-inhibitors-to-identify-drug-targets-for-polycystic-kidney-disease
#1
Tijmen H Booij, Hester Bange, Wouter N Leonhard, Kuan Yan, Michiel Fokkelman, Steven J Kunnen, Johannes G Dauwerse, Yu Qin, Bob van de Water, Gerard J P van Westen, Dorien J M Peters, Leo S Price
Polycystic kidney disease (PKD) is a prevalent disorder characterized by renal cysts that lead to kidney failure. Various signaling pathways have been targeted to stop disease progression, but most interventions still focus on alleviating PKD-associated symptoms. The mechanistic complexity of the disease, as well as the lack of functional in vitro assays for compound testing, has made drug discovery for PKD challenging. To identify modulators of PKD, Pkd1(-/-) kidney tubule epithelial cells were applied to a scalable and automated 3D cyst culture model for compound screening, followed by phenotypic profiling to determine compound efficacy...
June 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28614117/role-of-amp-activated-protein-kinase-in-kidney-tubular-transport-metabolism-and-disease
#2
Roshan Rajani, Nuria M Pastor-Soler, Kenneth R Hallows
PURPOSE OF REVIEW: AMP-activated protein kinase (AMPK) is a metabolic sensor that regulates cellular energy balance, transport, growth, inflammation, and survival functions. This review explores recent work in defining the effects of AMPK on various renal tubular epithelial ion transport proteins as well as its role in kidney injury and repair in normal and disease states. RECENT FINDINGS: Recently, several groups have uncovered additional functions of AMPK in the regulation of kidney and transport proteins...
June 12, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28577072/regulation-of-renal-na-k-cl-cotransporters-by-vasopressin
#3
REVIEW
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...
June 2, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28533908/ascites-refractory-ascites-and-hyponatremia-in-cirrhosis
#4
Brett Fortune, Andres Cardenas
Ascites is the most common complication related to cirrhosis and is associated with increased morbidity and mortality. Ascites is a consequence of the loss of compensatory mechanisms to maintain the overall effective arterial blood volume due to worsening splanchnic arterial vasodilation as a result of clinically significant portal hypertension. In order to maintain effective arterial blood volume, vasoconstrictor and antinatriuretic pathways are activated, which increase overall sodium and fluid retention...
May 2017: Gastroenterology Report
https://www.readbyqxmd.com/read/28507058/hepatocyte-nuclear-factor-1%C3%AE-regulates-urinary-concentration-and-response-to-hypertonicity
#5
Karam Aboudehen, Lama Noureddine, Patricia Cobo-Stark, Svetlana Avdulov, Shayan Farahani, Micah D Gearhart, Daniel G Bichet, Marco Pontoglio, Vishal Patel, Peter Igarashi
The transcription factor hepatocyte nuclear factor-1β (HNF-1β) is essential for normal kidney development and function. Inactivation of HNF-1β in mouse kidney tubules leads to early-onset cyst formation and postnatal lethality. Here, we used Pkhd1/Cre mice to delete HNF-1β specifically in renal collecting ducts (CDs). CD-specific HNF-1β mutant mice survived long term and developed slowly progressive cystic kidney disease, renal fibrosis, and hydronephrosis. Compared with wild-type littermates, HNF-1β mutant mice exhibited polyuria and polydipsia...
May 15, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28501079/functional-magnetic-resonance-imaging-of-the-kidneys-with-and-without-gadolinium-based-contrast
#6
REVIEW
Jeff L Zhang
Assessment of renal function with magnetic resonance imaging (MRI) has been actively explored in the past decade. In this review, we introduce the principle of MRI and review recent progress of MRI methods (contrast enhanced and noncontrast) in assessing renal function. Contrast-enhanced MRI using ultra-low dose of gadolinium-based agent has been validated for measuring single-kidney glomerular filtration rate and renal plasma flow accurately. For routine functional test, contrast-enhanced MRI may not replace the simple serum-creatinine method...
May 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/28493905/melioidosis-clinical-impact-and-public-health-threat-in-the-tropics
#7
REVIEW
Ramar Perumal Samy, Bradley G Stiles, Gautam Sethi, Lina H K Lim
This review briefly summarizes the geographical distribution and clinical impact of melioidosis, especially in the tropics. Burkholderia pseudomallei (a gram-negative bacterium) is the major causative agent for melioidosis, which is prevalent in Singapore, Malaysia, Thailand, Vietnam, and Northern Australia. Melioidosis patients are increasingly being recognized in other parts of the world. The bacteria are intrinsically resistant to many antimicrobial agents, but prolonged treatment, especially with combinations of antibiotics, may be effective...
May 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28468519/atrasentan-for-the-treatment-of-diabetic-nephropathy
#8
REVIEW
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
https://www.readbyqxmd.com/read/28414662/weil-s-disease-from-a-local-new-orleans-bar
#9
H P Kahn, L Bateman
INTRODUCTION: Leptospirosis is a zoonotic infection that typically presents with fever, myalgias, nausea, and vomiting after contact with contaminated waters or infected animals (typically rodents); and their excrements. Conditions favorable to the transmission of leptospirosis are common in LA and, without treatment, leptospirosis can lead to both liver and renal failure, meningitis, pulmonary hemorrhage and ultimately death. CASE: A 56 year old woman with no past medical history presented to the Emergency Department with weakness, myalgias, jaundice and decreased urine output for one week...
March 2017: Journal of the Louisiana State Medical Society: Official Organ of the Louisiana State Medical Society
https://www.readbyqxmd.com/read/28397867/oxidative-stress-causes-hypertension-and-activation-of-nuclear-factor-%C3%AE%C2%BAb-after-high-fructose-and-salt-treatments
#10
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
https://www.readbyqxmd.com/read/28341273/branched-chain-amino-acids-enhance-cyst-development-in-autosomal-dominant-polycystic-kidney-disease
#11
Junya Yamamoto, Saori Nishio, Fumihiko Hattanda, Daigo Nakazawa, Toru Kimura, Michio Sata, Minoru Makita, Yasunobu Ishikawa, Tatsuya Atsumi
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney and liver cysts. The mammalian target of rapamycin (mTOR) cascade is one of the important pathways regulating cyst growth in ADPKD. Branched-chain amino acids (BCAAs), including leucine, play a crucial role to activate mTOR pathway. Therefore, we administered BCAA dissolved in the drinking water to Pkd1(flox/flox):Mx1-Cre (cystic) mice from four to 22 weeks of age after polyinosinic-polycytidylic acid-induced conditional Pkd1 knockout at two weeks of age...
March 21, 2017: Kidney International
https://www.readbyqxmd.com/read/28318631/the-antihelmenthic-phosphate-niclosamide-impedes-renal-fibrosis-by-inhibiting-homeodomain-interacting-protein-kinase-2-expression
#12
Xiaoyan Chang, Xin Zhen, Jixing Liu, Xiaomei Ren, Zheng Hu, Zhanmei Zhou, Fengxin Zhu, Ke Ding, Jing Nie
Renal fibrosis is the final common pathway of all varieties of progressive chronic kidney disease. However, there are no effective therapies to prevent or slow the progression of renal fibrosis. Niclosamide is a US Food and Drug Administration-approved oral antihelminthic drug used for treating most tapeworm infections. Here, we demonstrated that phosphate niclosamide, the water-soluble form of niclosamide, significantly reduced proteinuria, glomerulosclrotic lesions, and interstitial fibrosis in a murine model of adriamycin nephropathy...
March 16, 2017: Kidney International
https://www.readbyqxmd.com/read/28293259/influence-of-normo-and-hypogonadal-condition-hyperuricemia-and-high-fructose-diet-on-renal-changes-in-male-rats
#13
Jimena Soutelo, Yanina Alejandra Samaniego, Elsa Zotta, María Cecilia Fornari, Carlos Reyes Toso, Osvaldo Juan Ponzo
Background. There is a gender disparity in the incidence, prevalence, and progression of renal disease. The object of this paper is to evaluate the presence and type of renal lesion in normogonadic and hypogonadic male rats in a mild hyperuricemia induced condition and exposed to a high-fructose diet. Methods. 56 adult male Wistar rats were used. Animals were divided into two groups, one normogonadic (NGN) and one hypogonadic (HGN), and each group was divided into four subgroups in accordance with the treatment: control with only water (C), fructose (F), oxonic acid (OA), and fructose + oxonic acid (FOA)...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28271257/outcomes-of-diuretic-use-in-pre-dialysis-ckd-patients-with-moderate-renal-deterioration-attending-tertiary-care-referral-center
#14
Yusra Habib Khan, Azmi Sarriff, Azreen Syazril Adnan, Amer Hayat Khan, Tauqeer Hussain Mallhi
INTRODUCTION: Diuretic therapy has been the mainstay of treatment in chronic kidney disease (CKD) patients, primarily for hypertension and fluid overload. Apart from their beneficial effects, diuretic use is associated with adverse renal outcomes. The current study is aimed to determine the outcomes of diuretic therapy. METHODOLOGY: A prospective observational study was conducted by inviting pre-dialysis CKD patients. Fluid overload was assessed by Bioimpedance analysis (BIA)...
March 7, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28177677/mtorc1-inhibitors-rapamycin-and-metformin-affect-cardiovascular-markers-differentially-in-zdf-rats
#15
COMPARATIVE STUDY
Ravi Nistala, Ahmad Raja, Lakshmi Pulakat
Mammalian target for rapamycin complex 1 (mTORC1) is a common target for the action of immunosuppressant macrolide rapamycin and glucose-lowering metformin. Inhibition of mTORC1 can exert both beneficial and detrimental effects in different pathologies. Here, we investigated the differential effects of rapamycin (1.2 mg/kg per day delivered subcutaneously for 6 weeks) and metformin (300 mg/kg per day delivered orally for 11 weeks) treatments on male Zucker diabetic fatty (ZDF) rats that mimic the cardiorenal pathology of type 2 diabetic patients and progress to insulin insufficiency...
March 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28137609/dietary-nitrate-load-lowers-blood-pressure-and-renal-resistive-index-in-patients-with-chronic-kidney-disease-a-pilot-study
#16
Stephan Kemmner, Georg Lorenz, Jana Wobst, Thorsten Kessler, Ming Wen, Roman Günthner, Konrad Stock, Uwe Heemann, Klaus Burkhardt, Marcus Baumann, Christoph Schmaderer
Beetroot has a high concentration of inorganic nitrate, which can serially reduced to form nitrite and nitric oxide (NO) after oral ingestion. Increased renal resistive index (RRI) measured by Doppler ultrasonography is associated with higher cardiovascular mortality in hypertensive patients with reduced renal function over time defined as chronic kidney disease (CKD). Our aim was to investigate whether the supplementation of dietary nitrate by administration of beetroot juice is able to reduce blood pressure and renal resistive index (RRI) as prognostic markers for cardiovascular mortality in CKD patients...
April 1, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28104100/pathophysiologic-mechanisms-in-heart-failure-role-of-the-sympathetic-nervous-system
#17
REVIEW
Steve Antoine, Gaurang Vaidya, Haider Imam, Daniel Villarreal
The syndrome of heart failure involves complex pathophysiologic mechanisms and is associated with extremely high-morbidity, mortality and economic costs. This growing global epidemic has diverse etiologies and is fundamentally characterized by dyshomeostasis between heart and kidneys, leading to development and progression of the cardiorenal syndrome. Excessive and sustained sympathoexcitation has emerged as a single prominent factor involved in the structural and functional dysfunction of multiple organ systems during this disease...
January 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28081165/urine-concentrating-capacity-vasopressin-and-copeptin-in-adpkd-and-iga-nephropathy-patients-with-renal-impairment
#18
Debbie Zittema, Niek F Casteleijn, Stephan J L Bakker, Lianne S M Boesten, A A Margreeth Duit, Casper F M Franssen, Carlo A J M Gaillard, Ron T Gansevoort
BACKGROUND: Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients have an impaired urine concentrating capacity. Increased circulating vasopressin (AVP) concentrations are supposed to play a role in the progression of ADPKD. We hypothesized that ADPKD patients have a more severely impaired urine concentrating capacity in comparison to other patients with chronic kidney disease at a similar level of kidney function, with consequently an enhanced AVP response to water deprivation with higher circulating AVP concentrations...
2017: PloS One
https://www.readbyqxmd.com/read/28057871/copeptin-a-surrogate-marker-for-arginine-vasopressin-is-associated-with-disease-severity-and-progression-in-iga-nephropathy-patients
#19
Debbie Zittema, Jan A J G van den Brand, Stephan J L Bakker, Jack F Wetzels, Ron T Gansevoort
Background.: Besides its essential role for water homeostasis, arginine vasopressin (AVP) may have deleterious effects on the kidney. Copeptin, a surrogate marker for AVP, has been shown to be related to renal outcome in patients with diabetic nephropathy and polycystic kidney disease. We investigated the association of copeptin with disease severity and progression in immunoglobulin A nephropathy (IgAN). Methods.: We included a prospective cohort of 59 patients with biopsy proven IgAN...
January 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27982262/characterization-of-an-experimental-model-of-progressive-renal-disease-in-rats
#20
Nilo César do Vale Baracho, Lucas Miranda Kangussu, Thiago Ruiz Rodrigues Prestes, Kátia Daniela da Silveira, Regina Maria Pereira, Natália Pessoa Rocha, Ana Cristina Simões E Silva
PURPOSE: To characterize an experimental model of progressive renal disease induced by different degrees of nephrectomy in rats. METHODS: Eighty male Wistar rats were divided into four experimental groups (n=20/group): sham surgery (control group), progressive degrees of nephrectomy leading to mild uremia (group 1), moderate uremia (group 2) and severe uremia (group 3). Ten animals of each group were followed for two or four weeks. At the end, blood and 24-hour urine samples were collected to determine renal function parameters...
November 2016: Acta Cirúrgica Brasileira
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