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American Journal of Physiology. Renal Physiology

Karl A Nath, Daniel R O'Brien, Anthony J Croatt, Joseph P Grande, Allan W Ackerman, Meryl C Nath, Satsuki Yamada, Andre Terzic, Tamara Tchkonia, James L Kirkland, Zvonimir S Katusic
There is no therapy that promotes maturation and functionality of a dialysis arteriovenous fistula (AVF). The search for such therapies largely relies on evaluating vascular responses and putative therapies in experimental AVFs. We studied an AVF in mice with chronic kidney disease (CKD). We demonstrate numerous stressors in the vein of the AVF-CKD group, including pathologic shear, mitogenic, inflammatory, and hypoxia-reoxygenation stress. Because stress promotes premature senescence, we examined whether senescence is induced in the vein of the AVF-CKD model...
July 18, 2018: American Journal of Physiology. Renal Physiology
Jiliang Wen, Shulu Zu, Zhenghao Chen, Stephanie L Daugherty, William C de Groat, Yuqiang Liu, Mingzhen Yuan, Guanghui Cheng, Xiulin Zhang
Literature documents an age related reduction of bladder sensory function. TRPV1 or TRPV4 channels have been implicated in bladder mechano-transduction. To investigate contributions of TRPV1 or TRPV4 to the age related reduction of bladder sensory function, bladder responses to capsaicin (CAP, TRPV1 agonist) and GSK1016790A (GSK, TRPV4 agonist) in retired breeder (RB, 12-15 months) and young adult (2-3 month) female rats were compared using multiple methods. Metabolic cage and continuous infusion cystometry (CMG) recordings revealed that RB rats exhibit larger bladder capacity and lower voiding frequency...
July 18, 2018: American Journal of Physiology. Renal Physiology
Tristan M Nicholson, Jalissa L Nguyen, Glen E Leverson, Julia A Taylor, Frederik S Vom Saal, Ronald W Wood, William A Ricke
Estrogens, acting synergistically with androgens, are known from animal experiments to be important in lower urinary tract symptoms (LUTS) and benign prostate enlargement. Human exposure to environmental estrogens occurs throughout the lifespan, but the urologic health risks in men are largely unknown. Bisphenol-A (BPA) is an endocrine disruptor implicated in male urogenital malformations. Given the role of estrogens in male LUTS, we studied the effects of BPA administered in combination with testosterone (T) on the urinary voiding behavior of adult male mice...
July 18, 2018: American Journal of Physiology. Renal Physiology
Kevin T Yang, Tianxin Yang, J David Symons
The antidiuretic hormone vasopressin (VP) is produced by the hypothalamus, and is stored and secreted from the posterior pituitary. VP acts via VP type 2 receptors (V2Rs) on the basolateral membrane of principal cells of the collecting duct (CD) to regulate fluid permeability. The VP-evoked endocrine pathway is essential in determining urine concentrating capability. For example, a defect in any component of the VP signaling pathway can result in polyuria, polydipsia, and hypotonic urine, collectively termed diabetes insipidus (DI)...
July 18, 2018: American Journal of Physiology. Renal Physiology
Taihei Suzuki, Diana G Eng, Aaron D McClelland, Jeffrey W Pippin, Stuart J Shankland
Under certain circumstances, podocytes can be partially replaced following their loss in disease. The inability of podocytes to proliferate suggests that replacement derives from other cell types. Because Neural/glial antigen 2 (NG2) expressing cells can serve as progenitors in other organs, and because herein we showed increased NG2 staining in podocytes following their loss in experimental FSGS, we used lineage tracing in NG2-CreER tdTomato mice to test the hypothesis that partial podocyte replacement might derive from this cell population...
July 18, 2018: American Journal of Physiology. Renal Physiology
Karen Melissa Hallow, Peter J Greasley, Gabriel Helmlinger, Lulu Chu, Hiddo J L Heerspink, David W Boulton
The mechanisms of cardiovascular and renal protection observed in clinical trials of SGLT2 inhibitors (SGLT2i) are incompletely understood and likely multifactorial, including natriuretic, diuretic, and antihypertensive effects, glomerular pressure reduction, and lowering of plasma and interstitial fluid volume. To quantitatively evaluate the contribution of proposed SGLT2i mechanisms of action on changes in renal hemodynamics and volume status, we coupled a mathematical model of renal function and volume homeostasis with clinical data in healthy subjects administered 10 mg dapagliflozin once-daily...
July 18, 2018: American Journal of Physiology. Renal Physiology
Danika Krupp, Timm H Westhoff, Jonas Esche, Thomas Remer
Experimental data and observational studies in adults suggest that even subtle changes in acid-base balance, indicative of a higher systemic proton load, are related to higher blood pressure (BP) levels and an increased hypertension risk. However, these associations have not been investigated during growth. The kidney is the central organ in regulating excretion of non-volatile acids and renal citrate excretion has been shown to be a sensitive non-invasive marker of changes in systemic acid-balance. We thus analysed the prospective relation of 24-h citrate excretion as well as net acid excretion capacity (NAEC, a non-invasive indicator of the renal ability to excrete protons) during adolescence (males: 10-15 years, females: 9-14 years) with BP-levels in young adulthood (18-30 years) in 374 healthy participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study...
July 18, 2018: American Journal of Physiology. Renal Physiology
Tafadzwa Chihanga, Hannah N Ruby, Qing Ma, Sabina Bashir, Prasad Devarajan, Michael A Kennedy
Acute kidney injury (AKI) can be caused by multiple factors including sepsis, respiratory failure, heart failure, trauma, or nephrotoxic medications, among others. Here, a mouse model was used to investigate potential urinary metabolic biomarkers of hypoxia-induced AKI. Urine metabolic profiles of 48 Swiss Webster mice were assessed using nuclear magnetic resonance spectroscopy (NMR) for 7 days following 72 hours exposure to a hypoxic 6.5% oxygen environment. Histological analyses indicated a lack of gross nephron structural changes in the aftermath of hypoxia...
July 11, 2018: American Journal of Physiology. Renal Physiology
Takahiro Uchida, Hiroyuki Nakashima, Seigo Ito, Takuya Ishikiriyama, Masahiro Nakashima, Shuhji Seki, Hiroo Kumagai, Naoki Oshima
Although activation of mouse natural killer T (NKT) cells by alpha-galactosylceramide (α-GalCer) causes failure of multiple organs, including the kidneys, precise mechanisms underlying kidney injury remain unclear. Here, we showed that α-GalCer-activated mouse NKT cells injured both kidney vascular endothelial cells and tubular epithelial cells in vitro, causing acute kidney injury (AKI) with hematuria in middle-aged mice. Perforin-mediated pathway was mainly involved in glomerular endothelial cell injury, whereas TNF-α/Fas ligand pathway played an important role in the injury of tubular epithelial cells...
July 11, 2018: American Journal of Physiology. Renal Physiology
Noriko Ide, Rui Ye, Marie Courbebaisse, Hannes Olauson, Michael J Densmore, Tobias Larsson, Jun-Ichi Hanai, Beate Lanske
Phosphate homeostasis is primarily maintained in the renal proximal tubules where the expression of sodium/phosphate co-transporters (Npt2a and Npt2c) is modified by the endocrine actions of both FGF23 and PTH. However, the specific contribution of each regulatory pathway in the proximal tubules has not been fully elucidated in vivo. We have previously demonstrated that proximal tubule-specific deletion of the FGF23 co-receptor Klotho results in mild hyperphosphatemia with little to no change in serum levels of FGF23, 1,25(OH)2D3, and PTH...
July 11, 2018: American Journal of Physiology. Renal Physiology
Maarten Wester, Maaike K van Gelder, Jaap A Joles, Frank Simonis, Diënty H M Hazenbrink, Theo W M van Berkel, Koen R D Vaessen, Walther H Boer, Marianne C Verhaar, Karin G F Gerritsen
BACKGROUND: The key to success in developing a wearable dialysis device is a technique to safely and efficiently regenerate and re-use a small volume of dialysate in a closed-loop system. In a hemodialysis model in goats, we explored whether urea removal by electro-oxidation (EO) could be effectively and safely applied in vivo. METHODS: A miniature dialysis device was built, containing 1 or 2 'EO unit(s)', each with 10 graphite electrodes, with a cumulative electrode surface of 585 cm2/unit...
July 11, 2018: American Journal of Physiology. Renal Physiology
Sebastian Frische, Regine Chambrey, Francesco Trepiccione, Reza Zamani, Niels Marcussen, R Todd Alexander, Karsten Skjødt, Per Svenningsen, Henrik Dimke
The vacuolar-type H+-ATPase B1 subunit is heavily expressed in the intercalated cells of the collecting system, where it contributes to H+ transport, but has also been described in other segments of the renal tubule. This study aims to determine the localization of the B1 subunit of the vacuolar-type H+-ATPase in the early distal nephron, encompassing thick ascending limbs (TAL) and distal convoluted tubules (DCT) in human kidney and determine if the localization differs between rodents and humans. Antibodies directed against the H+-ATPase B1 subunit were used to determine its localization in paraffin embedded formalin fixed mouse, rat, and human kidneys by light microscopy and in sections of lowicryl embedded rat kidneys by electron microscopy...
July 11, 2018: American Journal of Physiology. Renal Physiology
Ruben Rodriguez, Andrew Lee, Keisa W Mathis, Hanna J Broome, Max Thorwald, Bridget Martinez, Daisuke Nakano, Akira Nishiyama, Michael J Ryan, Rudy M Ortiz
Pathological activation of the renin-angiotensin system and inflammation are associated with hypertension and the development of metabolic syndrome (MetS). The contributions of angiotensin receptor type 1 (AT1) activation, independent of blood pressure, and inflammation on glucose intolerance and renal damage are not well defined. Using a rat model of MetS, we hypothesized that the onset of glucose intolerance is primarily mediated by AT1 activation and inflammation independent of elevated systolic blood pressure (SBP)...
July 11, 2018: American Journal of Physiology. Renal Physiology
Kyle Allen Wegner, Lisa L Abler, Steven Royal Oakes, Guneet S Mehta, K Elaine Ritter, Warren G Hill, Bernadette M M Zwaans, Laura E Lamb, Zunyi Wang, Dale E Bjorling, William A Ricke, Jill Macoska, Paul C Marker, E Michelle Southard-Smith, Kevin W Eliceiri, Chad M Vezina
Mouse urinary behavior is quantifiable and used to pinpoint mechanisms of voiding dysfunction and evaluate potential human therapies. Approaches to evaluate mouse urinary function vary widely among laboratories, however, complicating cross-study comparisons. Here, we describe development and multi-institutional validation of a new tool for objective, consistent and rapid analysis of mouse void spot assay (VSA) data. Void Whizzard is a freely available software plugin for FIJI (a distribution of ImageJ) that facilitates VSA image batch processing and data extraction...
July 4, 2018: American Journal of Physiology. Renal Physiology
Donna Jayne Sellers, Catherine McDermott, Russ Chess-Williams
No abstract text is available yet for this article.
June 27, 2018: American Journal of Physiology. Renal Physiology
Ying Fu, Chengyuan Tang, Juan Cai, Guochun Chen, Dongshan Zhang, Zheng Dong
Acute kidney injury (AKI) is a contributing factor in the development and progression of chronic kidney disease (CKD). Despite rapid progresses, the mechanism underlying AKI- CKD transition remains largely unclear. Animal models recapitulating this process are crucial to the research of the pathophysiology of AKI-CKD transition and the development of effective therapeutics. In this review, we present the commonly used rodent models of AKI-CKD transition, including bilateral ischemia-reperfusion injury (bIRI), unilateral IRI (uIRI), unilateral IRI with contralateral nephrectomy (uIRIx), multiple episodes of IRI, and repeated treatment of low dose cisplatin, diphtheria toxin, aristolochic acid or folic acid...
June 27, 2018: American Journal of Physiology. Renal Physiology
Mark A Bryniarski, Benjamin M Yee, Irum Jaffri, Lee D Chaves, Jin Ah Yu, Xiaowen Guan, Nazanin Ghavam, Rabi Yacoub, Marilyn E Morris
The megalin/cubilin complex is responsible for the majority of serum protein reclamation in the proximal tubules. The current study examined if decreases in their renal expression, along with the albumin recycling protein FcRn, could account for proteinuria/albuminuria in the Zucker Diabetic Fatty rat model of type 2 diabetic nephropathy. Immunoblots of renal cortex samples obtained at worsening disease stages demonstrated no loss in megalin, cubilin, or FcRn, even when proteinuria was measured. Additionally, early diabetic rats exhibited significantly increased renal megalin expression when compared to controls (adjusted p < 0...
June 27, 2018: American Journal of Physiology. Renal Physiology
Alan M Weinstein
No abstract text is available yet for this article.
June 20, 2018: American Journal of Physiology. Renal Physiology
Kim Maree O'Sullivan, Sharon Lee Ford, Anthony Longano, A Richard Kitching, Stephen R Holdsworth
In anti-neutrophil cytoplasmic antibody associated vasculitis (AAV), toll like receptors (TLRs) may be engaged by infection associated patterns and by endogenous danger signals, linking infection and innate inflammation with this autoimmune disease. This study examined intrarenal TLR2, TLR4 and TLR9 expression and renal injury in AAV, testing the hypothesis that increased TLR expression correlates with renal injury. Patients with AAV exhibited both glomerular and tubulointerstitial expression of TLR2, TLR4 and TLR9, with TLR4 being the most prominent in both compartments...
June 20, 2018: American Journal of Physiology. Renal Physiology
Brandon A Kemp, Nancy L Howell, Shetal H Padia
The intrarenal ghrelin receptor (GR) is localized to collecting duct (CD) cells where it increases αENaC-dependent sodium reabsorption in rodents. We hypothesized that chronic GR inhibition with intrarenal GR siRNA lowers blood pressure (BP) in Angiotensin II-dependent hypertension via reductions in αENaC-dependent sodium reabsorption. Uninephrectomized Sprague-Dawley rats (N=121) received subcutaneous osmotic pumps for chronic systemic delivery of Angiotensin II or vehicle (5% dextrose in water). Rats also received intrarenal infusion of vehicle, GR siRNA, or scrambled (SCR) siRNA...
June 20, 2018: American Journal of Physiology. Renal Physiology
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