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American Journal of Physiology. Renal Physiology

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https://www.readbyqxmd.com/read/29212765/changes-in-the-fluid-volume-balance-between-intra-and-extracellular-water-in-a-sample-of-japanese-adults-aged-15-88-years-old-a-cross-sectional-study
#1
Yasushi Ohashi, Nobuhiko Joki, Keisuke Yamazaki, Takeshi Kawamura, Reibin Tai, Hideyo Oguchi, Rena Yuasa, Ken Sakai
The fluid volume balance between intracellular water (ICW) and extracellular water (ECW) gradually changes with age and various medical conditions. Comprehension of these physiological changes would aid in clinical decision-making related to body fluid assessments. A total of 1,992 individuals (753 men and 1,239 women) aged ≥15 years included in this study had their body composition measurements performed at training gyms in 2014. We developed a regression formula to assess the association of age with the ratio of ECW to ICW in these subjects...
December 6, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29212764/aberrant-dna-methylation-of-pregnane-x-receptor-underlies-metabolic-gene-alterations-in-the-diabetic-kidney
#2
Atsushi Watanabe, Takeshi Marumo, Wakako Kawarazaki, Mitsuhiro Nishimoto, Nobuhiro Ayuzawa, Kohei Ueda, Daigoro Hirohama, Toshiya Tanaka, Shintaro Yagi, Satoshi Ota, Genta Nagae, Hiroyuki Aburatani, Hiroo Kumagai, Toshiro Fujita
Epigenetic abnormalities have been suggested to mediate metabolic memory observed in diabetic complications. We have shown that epigenetic alterations may induce persistent phenotypic changes in the proximal tubules of the diabetic kidneys. In this study, we show that pregnane X receptor (PXR), a xenobiotic nuclear receptor, is epigenetically altered and upregulated, and may have a possible function in the diabetic kidney. PXR has been shown to play a critical role in metabolic changes in obesity and diabetes; however, its distribution and function in the kidney are unknown...
December 6, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29187373/klotho-activin-a-in-kidney-injury-plasma-klotho-is-maintained-in-unilateral-obstruction-despite-no-upregulation-of-klotho-biosynthesis-in-contralateral-kidney
#3
Anders Nordholm, Maria L Mace, Eva Gravesen, Jacob Hofman-Bang, Marya Morevati, Klaus Olgaard, Ewa Lewin
In a new paradigm of etiology related to Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) kidney injury may cause induction of factors in the injured kidney that are released into the circulation and thereby initiate and maintain renal fibrosis and CKD-MBD. Klotho is believed to ameliorate renal fibrosis and CKD-MBD, while ActivinA might have detrimental effects. The unilateral ureter obstruction (UUO) model is used here to examine this concept by investigating early changes related to renal fibrosis in obstructed kidney, untouched contralateral kidney and vasculature, which might be affected by secreted factors from the obstructed kidney, and compared to unilateral nephrectomized controls (UNX)...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29187372/renal-tubular-ace-mediated-tubular-injury-is-the-major-contributor-to-microalbuminuria-in-early-diabetic-nephropathy
#4
Masahiro Eriguchi, Mercury Lin, Michifumi Yamashita, Tuantuan V Zhao, Zakir Khan, Ellen A Bernstein, Susan B Gurley, Romer A Gonzalez-Villalobos, Kenneth E Bernstein, Jorge Fernando Giani
Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular versus glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29187371/effects-of-erythropoietin-receptor-activity-on-angiogenesis-tubular-injury-and-fibrosis-in-acute-kidney-injury-a-u-shaped-relationship
#5
Mingjun Shi, Brianna Flores, Peng Li, Nancy Gillings, Kathryn L McMillan, Jianfeng Ye, Lily June-Shen Huang, Sachdev S Sidhu, Yong-Ping Zhong, Maria T Grompe, Philip R Streeter, Orson W Moe, Ming Chang Hu
Erythropoietin receptor (EpoR) is widely expressed but its renoprotective action is unexplored. To examine the role of EpoR in vivo in the kidney, we induced acute kidney injury (AKI) by ischemia-reperfusion in mice with different EpoR bioactivities in the kidney. EpoR bioactivity was reduced by knock-in of wild type human EpoR, which is hypo-functional relative to murine EpoR, and a renal tubule-specific EpoR knockout. These mice had lower EPO/EpoR activity and lower autophagy flux in renal tubules. Upon AKI induction, they exhibited worse renal function and structural damage, and more apoptosis at the acute stage (< 7 days), and slower recovery with more tubulointerstitial fibrosis at the subacute stage (14 days)...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29187370/ste20-like-kinase-slk-a-novel-mediator-of-podocyte-integrity
#6
Andrey V Cybulsky, Joan Papillon, Julie Guillemette, Natalya Belkina, Genaro Patino-Lopez, Elena Torban
SLK is essential for embryonic development, and may play a key role in wound healing, tumor growth and metastasis. Expression and activation of SLK is increased in kidney development and during recovery from ischemic acute kidney injury. Overexpression of SLK in glomerular epithelial cells/podocytes in vivo induces injury and proteinuria. Conversely, reduced SLK expression leads to abnormalities in cell adhesion, spreading, and motility. Tight regulation of SLK expression thus may be critical for normal renal structure and function...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29187369/pharmacological-and-genetic-inhibition-of-downstream-targets-of-p38-mapk-in-experimental-nephrotic-syndrome
#7
Xiaojing Nie, Melinda A Chanley, Ruma Pengal, David B Thomas, Shipra Agrawal, William E Smoyer
The p38MAPK pathway plays a crucial role in various glomerulopathies, with activation being associated with disease and inhibition being associated with disease amelioration. We hypothesized that the downstream targets of p38MAPK, MK2 and/or MK3, play an important role in mediating injury in experimental nephrotic syndrome via their actions on their downstream substrates HSPB1 and COX-2. To test this hypothesis, the effects of both pharmacological and genetic inhibition of MK2 and MK3 were examined in mouse Adriamycin (ADR) and rat puromycin aminonucleoside (PAN) nephropathy models...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29187368/n-linked-glycans-are-required-on-epithelial-na-channel-subunits-for-maturation-and-surface-expression
#8
Ossama B Kashlan, Carol L Kinlough, Michael M Myerburg, Shujie Shi, Jingxin Chen, Brandon M Blobner, Teresa M Buck, Jeffrey L Brodsky, Rebecca P Hughey, Thomas R Kleyman
Epithelial Na+ channel (ENaC) subunits undergo N-linked glycosylation in the endoplasmic reticulum where they assemble into an αβγ complex. Six, thirteen and five consensus sites (Asn-x-Ser/Thr) for N-glycosylation reside in the extracellular domains of the mouse α, β and γ subunits, respectively. Because the importance of ENaC N-linked glycans has not been fully addressed, we examined the effect of preventing N-glycosylation of specific subunits on channel function, expression, maturation, and folding...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29187367/oxidative-stress-increases-megalin-expression-in-the-renal-proximal-tubules-during-the-normoalbuminuric-stage-of-diabetes-mellitus
#9
Yoshifumi Kurosaki, Akemi Imoto, Fumitaka Kawakami, Masanori Yokoba, Tsuneo Takenaka, Takafumi Ichikawa, Masato Katagiri, Naohito Ishii
Megalin, an endocytic receptor expressed in proximal tubule cells, plays a critical role in renal tubular protein reabsorption and is associated with in the albuminuria observed in diabetic nephropathy. We have previously reported increased oxidant production in the renal cortex during the normoalbuminuric stage of diabetes mellitus (DM); however, the relationship between oxidative stress and renal megalin expression during the normoalbuminuric stage of DM remains unclear. In the present study, we evaluated whether oxidative stress affects megalin expression in the normoalbuminuric stage of DM in a streptozotocin-induced diabetic rat model and in immortalized human proximal tubular cells (HK-2)...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29167172/podocytes-exhibit-a-specialized-protein-quality-control-employing-derlin-2-in-kidney-disease
#10
Guohui Ren, Nicholas J Tardi, Fumihiko Matsuda, Kwi Hye Koh, Phillip Ruiz, Changli Wei, Mehmet Mete Altintas, Hidde Ploegh, Jochen Reiser
Podocytes are terminally differentiated cells of the kidney filtration barrier with a limited proliferative capacity, and are the primary glomerular target for various sources of cellular stress. Accordingly, it is particularly important for podocytes to cope with stress efficiently to circumvent cell death and avoid compromising renal function. Improperly folded proteins within the endoplasmic reticulum (ER) are associated with increased cellular injury and cell death. To relieve ER stress, protein quality control mechanisms like ER-associated degradation (ERAD) are initiated...
November 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29167171/advances-in-our-understanding-of-the-pathogenesis-of-hemolytic-uremic-syndromes
#11
Emily Elizabeth Bowen, Richard John Mark Coward
Hemolytic uremic syndrome (HUS) is major global health care issue as it is the leading cause of acute kidney injury in children. It is a triad of acute kidney injury, microangiopathic hemolytic anemia and thrombocytopenia. It is classified as a glomerular thrombotic microangiopathy. In recent years major advances in our understanding of complement driven inherited rare forms of HUS have been achieved. However, 90% of cases of HUS are associated with a Shiga toxin producing enteric pathogen. The precise pathological mechanisms in this setting are yet to be elucidated...
November 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29167170/canagliflozin-reduces-plasma-uremic-toxins-and-alters-the-intestinal-microbiota-composition-in-a-chronic-kidney-disease-mouse-model
#12
Eikan Mishima, Shinji Fukuda, Yoshitomi Kanemitsu, Daisuke Saigusa, Chikahisa Mukawa, Kei Asaji, Yotaro Matsumoto, Hiroki Tsukamoto, Tatsuki Tachikawa, Tomoya Tsukimi, Noriko N Fukuda, Hsin-Jung Ho, Koichi Kikuchi, Chitose Suzuki, Fumika Nanto, Takehiro Suzuki, Sadayoshi Ito, Tomoyoshi Soga, Yoshihisa Tomioka, Takaaki Abe
Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium/glucose co-transporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice...
November 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29167169/cutting-edge-microangio-ct-new-dimensions-in-vascular-imaging-and-kidney-morphometry
#13
Ruslan Hlushchuk, Cédric Zubler, Sébastien Barré, Carlos Correa Shokiche, Laura Schaad, Raphael Röthlisberger, Monika L Wnuk, Christoph Daniel, Oleksiy Khoma, Stefan A Tschanz, Mauricio Reyes, Valentin Djonov
In the last decades the contrast-enhanced microCT-imaging of whole animal kidney became increasingly important. The visualization was mainly limited to middle-sized vessels. Since modern desktop microCT-scanners provide the necessary detail resolution, we developed an approach for rapid visualization and consistent assessment of kidney vasculature and glomeruli number. This method is based on μAngiofil®, a new polymerizing contrast agent with homogenous X-ray absorption, which provides continuous filling of the complete vasculature and enables correlative imaging approaches...
November 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29141941/insights-from-direct-renal-insulin-infusion-a-new-hammer-for-an-age-old-nail
#14
Jonathan M Nizar, Vivek Bhalla
N/A.
November 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29141940/the-effects-of-different-storage-solutions-on-renal-ischemia-tolerance-after-kidney-transplantation-in-mice
#15
Lei Wang, Jin Wei, Shan Jiang, Hui-Hua Li, Liying Fu, Jie Zhang, Ruisheng Liu
Cold storage is the most prevalent method for graft preservation in kidney transplantation (KTX). The protective effects of various preservation solutions have been extensively studied in both clinical trials and experimental animal models. However, a paucity of studies examined the effect of different preservation solutions on graft function in mouse KTX, in addition, the tolerance of the transplanted grafts to further insult has not been evaluated, which were the objectives of the present study. We performed mouse KTX in three groups with the donor kidneys preserved in different solutions for 60 minutes: saline, mouse serum, and University of Wisconsin (UW) solution...
November 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29141939/dapagliflozin-in-focal-segmental-glomerulosclerosis-a-combined-human-rodent-pilot-study
#16
Harindra Rajasekeran, Heather N Reich, Michelle A Hladunewich, Daniel Cattran, Julie A Lovshin, Yuliya Lytvyn, Petter Bjornstad, Vesta Lai, Josephine Tse, Leslie Cham, Syamantak Majumder, Bridgit B Bowskill, M Golam Kabir, Suzanne L Advani, Ian W Gibson, Manish M Sood, Andrew Advani, David Z I Cherney
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is an important cause of non-diabetic chronic kidney disease (CKD). Sodium glucose cotransporter-2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in non-diabetic CKD such as FSGS. OBJECTIVE: The primary aim of this pilot study was to determine the effect of 8 weeks of dapagliflozin on GFR in humans and in experimental FSGS...
November 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29141938/stimulation-of-the-sensory-pudendal-nerve-increases-bladder-capacity-in-the-rat
#17
James A Hokanson, Christopher L Langdale, Arun Sridhar, Warren M Grill
Pudendal nerve stimulation is a promising treatment approach for lower urinary tract dysfunction, including symptoms of overactive bladder. Despite some promising clinical studies, there remain many unknowns as to how best to stimulate the pudendal nerve to maximize therapeutic efficacy. We quantified changes in bladder capacity and voiding efficiency during single-fill cystometry in response to electrical stimulation of the sensory branch of the pudendal nerve in urethane-anesthetized female Wistar rats. Increases in bladder capacity were dependent on both stimulation amplitude and rate...
November 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29141937/novel-differences-in-renal-gene-expression-in-a-diet-induced-obesity-model
#18
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/29117997/metformin-an-anti-proliferative-agent-and-methylation-regulator-in-treating-prostatic-disease
#19
Zongwei Wang, Aria F Olumi
Existing drugs that have been used in clinical practice for other purposes can prove useful for reutilization, since much of the safety profile, pharmacokinetics have been completed. Therefore, the drugs can enter clinical practice for variety of causes with less regulatory burden. Metformin may prove to be such a drug where it may have a role in other diseases, beside management of diabetes. In this perspective, we provide our finding and understanding of metformin as an alternate way to treat urological abnormal proliferation...
November 8, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29117996/effect-of-isolated-ultrafiltration-and-isovolemic-dialysis-on-myocardial-perfusion-and-left-ventricular-function-assessed-with-13n-nh3-pet-and-echocardiography
#20
Solmaz Assa, Hannie Kuipers, Esmee Ettema, Carlo A Gaillard, Wim P Krijnen, Yoran M Hummel, Adriaan A Voors, Joost P van Melle, Ralf Westerhuis, Antoon Willemsen, Riemer H J A Slart, Casper Fm Franssen
Hemodialysis is associated with a fall in myocardial perfusion and may induce regional left ventricular (LV) systolic dysfunction. The pathophysiology of this entity is incompletely understood and the contribution of ultrafiltration and diffusive dialysis has not been studied. We investigated the effect of isolated ultrafiltration and isovolemic dialysis on myocardial perfusion and LV function. Eight patients (7 male, age 55±18 years) underwent 60 min of isolated ultrafiltration and 60 min of isovolemic dialysis in randomized order...
November 8, 2017: American Journal of Physiology. Renal Physiology
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