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https://www.readbyqxmd.com/read/29146141/the-myth-of-water-and-salt-from-aquaretics-to-tenapanor
#1
REVIEW
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
https://www.readbyqxmd.com/read/29145743/novel-avenues-for-drug-discovery-in-diabetic-kidney-disease
#2
Matthew D Breyer, Matthias Kretzler
Diabetic kidney disease (DKD) has emerged as major cause of morbidity and mortality. After progressing to renal failure, over 70% of DKD patients are dead with five years. New treatments to slow this progression are desperately needed. Areas covered: This review highlights the current treatment options for people with DKD with a particular focus on angiotensin pathway blockade and the potential use of sodium glucose linked transporter 2 (SGLT2) inhibitors. These treatments are associated with an initial decrease in glomerular filtration rate (GFR) and albuminuria; there is also attention on renal hyperfiltration as therapeutic target...
November 16, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/29141937/novel-differences-in-renal-gene-expression-in-a-diet-induced-obesity-model
#3
Victoria L Halperin Kuhns, Jennifer L Pluznick
Obesity is a significant risk factor for both chronic kidney disease and end stage renal disease. To better understand disease development, we sought to identify novel genes differentially expressed early in disease progression. We first confirmed that mice fed a high-fat (HF) diet exhibit early signs of renal injury including hyperfiltration. We then performed RNA Seq using renal cortex RNA from C57Bl/6 male mice fed either HF or control (Ctrl) diet. We identified 1134 genes differentially expressed in the cortex on HF versus Ctrl, of which 31 genes were selected for follow up analysis...
November 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29123192/targeted-mitochondrial-therapy-using-mitoq-shows-equivalent-renoprotection-to-angiotensin-converting-enzyme-inhibition-but-no-combined-synergy-in-diabetes
#4
Micheal S Ward, Nicole B Flemming, Linda A Gallo, Amelia K Fotheringham, Domenica A McCarthy, Aowen Zhuang, Peter H Tang, Danielle J Borg, Hannah Shaw, Benjamin Harvie, David R Briskey, Llion A Roberts, Manuel R Plan, Michael P Murphy, Mark P Hodson, Josephine M Forbes
Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29115052/dose-selection-based-on-modeling-and-simulation-for-rivipansel-in-pediatric-patients-aged-6-to-11-years-with-sickle-cell-disease
#5
Brinda K Tammara, Lutz O Harnisch
This modeling and simulation exercise aimed to provide dosing recommendations for rivipansel phase 3 studies in children aged 6 to 11 years with sickle cell disease (SCD). Pharmacokinetic data from 109 patients aged 12 to 51 years who received rivipansel (2-40 mg/kg) in previous studies (3 phase 1, one phase 2) were integrated to build a 3-compartmental simulation model. Renal clearance simulations across the age range accounted for renal function development and postulated hyperfiltration in SCD. Simulated demographic distributions for the pediatric SCD population were used to predict concentration-time profiles from 3 dosing regimens, which were then compared against efficacious average steady-state concentrations observed in phase 2...
November 8, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29072675/outcomes-of-prenatally-diagnosed-solitary-functioning-kidney-during-early-life
#6
M Davidovits, R Cleper, N Eizenberg, O Hocherman, R Mashiach
OBJECTIVE: To evaluate outcomes of congenital solitary functioning kidney (SFK) in early childhood. STUDY DESIGN: A retrospective study of 32 children diagnosed in utero with SFK owing to unilateral renal agenesis or multicystic dysplastic kidney and followed for 1 to 11.5 years. RESULTS: SFK length was in the compensatory hypertrophy range in 45% of fetal sonographic evaluations from mid-pregnancy, and in 85% on postnatal follow-up. Glomerular filtration rate was below normal range in 44...
October 26, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/29068795/the-role-of-renal-response-to-amino-acid-infusion-and-oral-protein-load-in-normal-kidneys-and-kidney-with-acute-and-chronic-disease
#7
Francis B Gabbai
PURPOSE OF REVIEW: High protein intake and hyperfiltration have been a focus of major interest as potential mechanism(s) of progression of renal disease. This review will examine: the renal response to a protein meal or amino acid infusion and its use to test the renal functional reserve (RFR); new methods to evaluate RFR; the use of RFR in various pathophysiologic conditions. RECENT FINDINGS: The renal response to protein/amino acid infusion involves several mechanisms, including nitric oxide, insulin, glucagon, arginine vasopressin, urea, the renal N-Methyl-D-Aspartate Glutamate receptor and modulation of the activity of the tubuloglomerular feedback system...
October 23, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29044509/comprehensive-transcriptome-analysis-of-fluid-shear-stress-altered-gene-expression-in-renal-epithelial-cells
#8
Steven J Kunnen, Tareq B Malas, Cornelis M Semeins, Astrid D Bakker, Dorien J M Peters
Renal epithelial cells are exposed to mechanical forces due to flow-induced shear stress within the nephrons. Shear stress is altered in renal diseases caused by tubular dilation, obstruction and hyperfiltration, which occur to compensate for lost nephrons. Fundamental in regulation of shear stress are primary cilia and other mechano-sensors, and defects in cilia formation and function have profound effects on development and physiology of kidneys and other organs. We applied RNA sequencing to get a comprehensive overview of fluid-shear regulated genes and pathways in renal epithelial cells...
October 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29031360/sodium-homeostasis-in-chronic-kidney-disease
#9
REVIEW
Vivek Soi, Jerry Yee
The pathologic consequences of sodium retention in the CKD population can lead to hypertension, edema, and progressive disease. Sodium excess is responsible for increases in oxidative stress, which alters kidney vasculature. As progression of CKD occurs, hyperfiltration by remaining nephrons compensates for an overall decrease in the filtered load of sodium. In the later stages of CKD, compensatory mechanisms are overcome and volume overload ensues. Nephrotic syndrome as it relates to sodium handling involves a different pathophysiology despite a common phenotype...
September 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29026873/graft-growth-and-podocyte-dedifferentiation-in-donor-recipient-size-mismatch-kidney-transplants
#10
Janina Müller-Deile, Jan Hinrich Bräsen, Marion Pollheimer, Manfred Ratschek, Hermann Haller, Lars Pape, Mario Schiffer
BACKGROUND: Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. METHODS: We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1) expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient...
October 2017: Transplantation Direct
https://www.readbyqxmd.com/read/29026688/establishing-the-presence-or-absence-of-chronic-kidney-disease-uses-and-limitations-of-formulas-estimating-the-glomerular-filtration-rate
#11
REVIEW
Ahmed Alaini, Deepak Malhotra, Helbert Rondon-Berrios, Christos P Argyropoulos, Zeid J Khitan, Dominic S C Raj, Mark Rohrscheib, Joseph I Shapiro, Antonios H Tzamaloukas
The development of formulas estimating glomerular filtration rate (eGFR) from serum creatinine and cystatin C and accounting for certain variables affecting the production rate of these biomarkers, including ethnicity, gender and age, has led to the current scheme of diagnosing and staging chronic kidney disease (CKD), which is based on eGFR values and albuminuria. This scheme has been applied extensively in various populations and has led to the current estimates of prevalence of CKD. In addition, this scheme is applied in clinical studies evaluating the risks of CKD and the efficacy of various interventions directed towards improving its course...
September 26, 2017: World Journal of Methodology
https://www.readbyqxmd.com/read/28992354/obesity-and-synergistic-risk-factors-for-chronic-kidney-disease-in-african-american-adults-the-jackson-heart-study
#12
Robert E Olivo, Clemontina A Davenport, Clarissa J Diamantidis, Nrupen A Bhavsar, Crystal C Tyson, Rasheeda Hall, Aurelian Bidulescu, Bessie Young, Stanford E Mwasongwe, Jane Pendergast, L Ebony Boulware, Julia J Scialla
Background: African Americans are at high risk for chronic kidney disease (CKD). Obesity may increase the risk for CKD by exacerbating features of the metabolic syndrome and promoting glomerular hyperfiltration. Whether other factors also affecting these pathways may amplify or mitigate obesity-CKD associations has not been investigated. Methods: We studied interactions between obesity and these candidate factors in 2043 African Americans without baseline kidney disease enrolled in the Jackson Heart Study...
August 30, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28992221/the-diabetes-pandemic-suggests-unmet-needs-for-ckd-with-diabetes-in-addition-to-diabetic-nephropathy-implications-for-pre-clinical-research-and-drug-testing
#13
Lidia Anguiano Gómez, Yutian Lei, Satish Kumar Devarapu, Hans-Joachim Anders
Curing 'diabetic nephropathy' is considered an unmet medical need of high priority. We propose to question the concept of 'diabetic nephropathy' that implies diabetes as the predominant cause of kidney disease, which may not apply to the majority of type 2 diabetics approaching end-stage kidney disease. With the onset of diabetes, hyperglycaemia/sodium-glucose co-transporter-2-driven glomerular hyperfiltration promotes nephron hypertrophy, which, however, on its own, causes proteinuria not before a decade later, probably because podocyte hypertrophy can usually accommodate an increase in the filtration surface...
July 31, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28978800/new-insights-on-glomerular-hyperfiltration-a-japanese-autopsy-study
#14
Go Kanzaki, Victor G Puelles, Luise A Cullen-McEwen, Wendy E Hoy, Yusuke Okabayashi, Nobuo Tsuboi, Akira Shimizu, Kate M Denton, Michael D Hughson, Takashi Yokoo, John F Bertram
It has been suggested that low nephron number contributes to glomerular hypertension and hyperperfusion injury in progressive chronic kidney disease (CKD). The incidence of CKD in Japan is among the highest in the world, but the reasons remain unclear. We estimated total nephron (glomerular) number (NglomTOTAL) as well as numbers of nonsclerosed (NglomNSG) and globally sclerosed glomeruli (NglomGSG), and the mean volume of nonsclerosed glomeruli (VglomNSG) in Japanese normotensive, hypertensive, and CKD subjects and investigated associations between these parameters and estimated glomerular filtration rate (eGFR)...
October 5, 2017: JCI Insight
https://www.readbyqxmd.com/read/28954992/nonconcordant-regulation-of-mitochondrial-respiratory-complexes-in-the-kidneys-of-5-6-nephrectomized-mice
#15
Yukie Nakashita, Tomoya Sano, Hiroaki Yoshioka, Tomoki Shimada, Ryotaro Hori, Makoto Usami, Yasuhiro Hamada
Hyperglycemia induces nonconcordant regulation of renal mitochondrial respiratory complexes, increases oxidative stress, and causes diabetic nephropathy. Hypertension is a complication associated with diabetes and involves glomerular hyperfiltration, the effects of which on mitochondrial respiratory complexes are not well understood. To investigate the effect of glomerular hyperfiltration on renal mitochondrial respiratory complexes, we used the 5/6 nephrectomized BKS. Cg-Dock7(m)+/+Lepr(db)/J, Dock7(m)+/+Lepr(db) mice (db/m-5/6Nx mice) as a model for glomerular hyperfiltration...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28951038/losartan-therapy-decreases-albuminuria-with-stable-glomerular-filtration-and-permselectivity-in-sickle-cell-anemia
#16
Marianne E Yee, Peter A Lane, David R Archer, Clinton H Joiner, James R Eckman, Antonio Guasch
Sickle cell nephropathy begins with hyperfiltration and microalbuminuria and may progress to renal failure. The aim of this study was to determine the effects of losartan on glomerular function and albumin excretion in sickle cell anemia (SCA). Individuals with SCA on hydroxyurea with persistent albuminuria were enrolled in a 1-year study of losartan. Glomerular filtration rate (GFR) measured by iohexol clearance, albumin excretion rate (AER), and fractional clearance of dextran were assessed at baseline, short-term (1-2month), and long-term (≥12month) intervals...
September 21, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28939448/-solitary-kidney-management-and-outcome
#17
A Godron-Dubrasquet, C Didailler, J Harambat, B Llanas
Solitary functioning kidneys form an important subgroup of congenital anomalies of the kidney and urinary tract (CAKUT). A solitary kidney can be congenital or acquired after unilateral nephrectomy and is often associated with ipsilateral urogenital anomalies. Both types of solitary functioning kidney are associated with an increased risk of chronic kidney disease (CKD). A low functional nephron number results in compensatory glomerular hypertension and enlargement of remnant nephrons, indicating glomerular hyperfiltration...
November 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/28935213/glomerular-hyperfiltration-is-a-predictor-of-adverse-cardiovascular-outcomes
#18
Gianpaolo Reboldi, Paolo Verdecchia, Gioia Fiorucci, Lawrence J Beilin, Kazuo Eguchi, Yutaka Imai, Kazuomi Kario, Takayoshi Ohkubo, Sante D Pierdomenico, Joseph E Schwartz, Lindon Wing, Francesca Saladini, Paolo Palatini
The association between glomerular hyperfiltration and cardiovascular events is not well known. To investigate whether glomerular hyperfiltration is independently associated with risk of adverse outcome we analyzed 8794 participants, average age 52 years enrolled in 8 prospective studies. Of these, 89% had hypertension. Using the 5th and 95th percentiles of the age- and sex-specific quintiles of CKD-EPI-calculated estimated glomerular filtration rate (eGFR), we identified three participant groups with low, high and normal eGFR...
September 18, 2017: Kidney International
https://www.readbyqxmd.com/read/28918991/comment-on-determinants-associated-with-the-correction-of-glomerular-hyperfiltration-one-year-after-bariatric-surgery
#19
EDITORIAL
Christopher R Daigle
No abstract text is available yet for this article.
October 2017: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28883987/obesity-and-kidney-disease-hidden-consequences-of-the-epidemic
#20
REVIEW
Csaba P Kovesdy, Susan L Furth, Carmine Zoccali
Obesity has become a worldwide epidemic, and its prevalence has been projected to grow by 40% in the next decade. This increasing prevalence has implications for the risk of diabetes, cardiovascular disease and also for chronic kidney disease. A high BMI is one of the strongest risk factors for new-onset chronic kidney disease. In individuals affected by obesity, a compensatory hyperfiltration occurs to meet the heightened metabolic demands of the increased body weight. The increase in intraglomerular pressure can damage the kidneys and raise the risk of developing chronic kidney disease in the long-term...
August 2017: Future Science OA
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