Bladder decompensation and reduction in nerve density in a rat model of chronic bladder outlet obstruction is attenuated with the NLRP3 inhibitor glyburide.
Abstract Bladder outlet obstruction (BOO) leads to progressive voiding dysfunction. Acutely, obstruction triggers inflammation that drives bladder dysfunction. Over time, inflammation leads to decreased bladder nerve density and increased fibrosis that is responsible for eventual decompensation and irreversibility. We have previously shown that BOO triggers inflammation, reduced bladder nerve density and increased fibrosis via activation of the NLRP3 inflammasome in an acutely obstructed (12 day) rat model. However, as BOO progresses the bladder may become decompensated with an increase in post-void residual volum...
Source: Am J Physiol Renal P... - October 24, 2018 Category: Urology & Nephrology Authors: Hughes FM, Sexton SJ, Ledig PD, Yun CE, Jin H, Purves JT Tags: Am J Physiol Renal Physiol Source Type: research

Renal tubular effects of prolonged therapy with the GLP-1 receptor agonist lixisenatide in patients with type 2 diabetes mellitus.
In conclusion, lixisenatide affects postprandial urinary excretion of several electrolytes and increases urinary pH compared to insulin glulisine in T2DM patients after 8 weeks of treatment. This is most likely explained by a drug-induced rise in blood pressure, or direct inhibitory effects on NHE3 in the proximal tubule. PMID: 30353743 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - October 24, 2018 Category: Urology & Nephrology Authors: Tonneijck L, Muskiet MHA, Blijdorp CJ, Smits MM, Twisk JW, Kramer MHH, Danser AHJ, Diamant M, Joles JA, Hoorn EJ, van Raalte DH Tags: Am J Physiol Renal Physiol Source Type: research

Periostin overexpression in collecting ducts accelerates renal cyst growth and fibrosis in polycystic kidney disease.
Abstract In polycystic kidney disease (PKD), persistent activation of cell proliferation and matrix production contributes to cyst growth and fibrosis, leading to progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is overexpressed by cystic epithelial cells of PKD kidneys. Periostin binds αVβ3-integrins and activates integrin-linked kinase (ILK), leading to Akt/mTOR-mediated proliferation of human PKD cells. By contrast, periostin does not stimulate the proliferation of normal human kidney cells. This difference in the re...
Source: Am J Physiol Renal P... - October 17, 2018 Category: Urology & Nephrology Authors: Raman A, Parnell SC, Zhang Y, Reif GA, Dai Y, Khanna A, Daniel E, White C, Vivian JL, Wallace DP Tags: Am J Physiol Renal Physiol Source Type: research

What we need to know about lipid-associated injury in case of renal ischemia/reperfusion.
Abstract Renal segmental metabolism is reflected by the complex distribution of the main energy pathways along the nephron, with fatty acid oxidation preferentially used in the cortex area. Ischemia/reperfusion injury (IRI) is due to the restriction of renal blood flow, rapidly leading to a metabolic switch towards anaerobic conditions. Subsequent unbalance between energy demand and oxygen/nutrient delivery compromises kidney cell functions, resulting to a complex inflammatory cascade including the production of reactive oxygen species (ROS). Renal IRI especially involves lipid accumulation. Lipid peroxidation is ...
Source: Am J Physiol Renal P... - October 17, 2018 Category: Urology & Nephrology Authors: Erpicum P, Rowart P, Defraigne JO, Krzesinski JM, Jouret F Tags: Am J Physiol Renal Physiol Source Type: research

APOL1 polymorphisms and kidney disease: Loss-of-function or gain-of-function?
Abstract The mechanism that explains the association of APOL1 variants with non-diabetic kidney diseases in African Americans remains unclear. Kidney disease risk is inherited as a recessive trait and many studies investigating the intracellular function of APOL1 have indicated the APOL1 variants G1 and G2 are associated with cytotoxicity. Whether cytotoxicity results from the absence of a protective effect conferred by the G0 allele or induced by a deleterious effect of variant allele expression has not be conclusively established. A central issue hampering basic biology studies is the lack of model systems that ...
Source: Am J Physiol Renal P... - October 17, 2018 Category: Urology & Nephrology Authors: Bruggeman LA, O'Toole JF, Sedor J Tags: Am J Physiol Renal Physiol Source Type: research

Blockade of Prostaglandin E2 Receptor 4 Ameliorates Nephrotoxic Serum Nephritis.
Eller K Abstract Prostaglandin E2 (PGE2) signaling is known to modulate inflammation and vascular resistance. Receptors of PGE2 (E-type prostanoid receptors, EP) might be an attractive pharmacological target in immune-mediated diseases such as glomerulonephritis. We hypothesized that selective EP4 antagonism improves nephrotoxic serum nephritis (NTS) by its anti-inflammatory properties. Mice were subjected to NTS and treated with the EP4 antagonist ONO AE3-208 [10 mg/kg bw/day] or vehicle starting from disease initiation. In one set of experiments treatment was started 4 days after NTS induction. Tubular epithelia...
Source: Am J Physiol Renal P... - October 17, 2018 Category: Urology & Nephrology Authors: Aringer I, Artinger K, Kirsch AH, Schabhüttl C, Jandl K, Bärnthaler T, Mooslechner A, Herzog SA, Uhlig M, Kirsch A, Frank S, Banas M, Pollheimer M, Eller P, Rosenkranz AR, Heinemann A, Eller K Tags: Am J Physiol Renal Physiol Source Type: research

NFAT5 regulates renal gene expression in response to Angiotensin II through Annexin-A2-mediated post-transcriptional regulation in hypertensive rats.
In conclusion, we show that ANGII increases Annexin-A2 nucleic acid binding activity that correlates with elevated protein levels of the NFAT5 transcription factor. NFAT signalling appears to be a major contributor to renal gene regulation in high-renin states. PMID: 30332317 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - October 17, 2018 Category: Urology & Nephrology Authors: Fähling M, Paliege A, Jönsson S, Becirovic-Agic M, Melville JM, Skogstrand T, Hultström M Tags: Am J Physiol Renal Physiol Source Type: research

Serum and Urinary SOD3 in Patients with Type 2 Diabetes: Comparison with Early Chronic Kidney Disease and Association with Development of Diabetic Nephropathy.
Abstract Extracellular superoxide dismutase (SOD3), one member of the antioxidant defense system and a superoxide scavenger, has been noted to be downregulated in the kidneys of diabetic mice and is characterized by a heparin-binding domain that can anchor the protein to the endothelium and extracellular matrix. The association of the serum and urinary SOD3 levels with diabetic nephropathy in different stages has never been evaluated. It remains unclear how urinary SOD3 changes in different renal diseases. We recruited 98 Taiwanese patients with type 2 diabetes and 10 patients with early chronic kidney disease (CK...
Source: Am J Physiol Renal P... - October 10, 2018 Category: Urology & Nephrology Authors: Kuo CW, Chen HL, Tu MY, Chen CM Tags: Am J Physiol Renal Physiol Source Type: research

A conditionally immortalized Gli1-positive kidney mesenchymal cell line models myofibroblast transition.
ys BD Abstract Gli1-positive resident mesenchymal stem cell-like cells are the predominant source of kidney myofibroblasts in fibrosis but investigating Gli1-positive myofibroblast progenitor activation is hampered by the difficulty of isolating and propagating primary cultures of these cells. Using a genetic strategy with positive and negative selection, we isolated Kidney-Gli1 (KG1) cells that maintain expression of appropriate mesenchymal stem cell-like cell markers, respond to hedgehog pathway activation and display robust myofibroblast differentiation upon treatment with TGFb. Co-culture of KG1 cells with end...
Source: Am J Physiol Renal P... - October 10, 2018 Category: Urology & Nephrology Authors: Ó hAinmhire E, Wu H, Muto Y, Donnelly EL, G Machado F, Fan LX, Chang-Panesso M, Humphreys BD Tags: Am J Physiol Renal Physiol Source Type: research

Reflections on the Void: The Art of Micturition Analysis.
PMID: 30303715 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - October 10, 2018 Category: Urology & Nephrology Authors: Fashemi BE, Mysorekar IU Tags: Am J Physiol Renal Physiol Source Type: research

Immune cells and inflammation in AKI to CKD progression.
Abstract Acute kidney injury (AKI) is a common clinical state resulting from pathogenic conditions such as ischemic and toxic insults. The pathophysiology of AKI shares common pathogenic denominators including cell death/injury, inflammation, and fibrosis, regardless of the initiating insults. Recent clinical studies have shown that a single episode of AKI can lead to subsequent chronic kidney disease (CKD). Although the involvement of multiple types of cells in the pathophysiology of AKI is becoming increasingly clear, the precise mechanisms for this "AKI to CKD progression" are still unknown, and no dr...
Source: Am J Physiol Renal P... - August 29, 2018 Category: Urology & Nephrology Authors: Sato Y, Yanagita M Tags: Am J Physiol Renal Physiol Source Type: research

Nephron-specific knockout of TMEM16A leads to reduced number of glomeruli and albuminuria.
Abstract TMEM16A is a transmembrane protein from a conserved family of calcium activated proteins, which is highly expressed in the kidney. TMEM16A confers calcium-activated chloride channel activity which is of importance for various cellular functions in secretory epithelia and involved in secretion-dependent renal cyst growth. However, its specific function in renal physiology has remained elusive so far. Therefore we generated conditional nephron specific TMEM16A knockout mice and found that these animals suffered from albuminuria. Kidney histology demonstrated an intact corticomedullary differentiation and ab...
Source: Am J Physiol Renal P... - August 29, 2018 Category: Urology & Nephrology Authors: Schenk LK, Buchholz B, Henke SF, Michgehl U, Daniel C, Amann K, Kunzelmann K, Pavenstadt HJ Tags: Am J Physiol Renal Physiol Source Type: research

The void spot assay: Recommendations on the use of a simple micturition assay for mice.
Abstract Investigators have for decades used mouse voiding patterns as endpoints for studying behavioral biology. It is only recently that mouse voiding patterns were adopted for study of lower urinary tract physiology. The spontaneous void spot assay (VSA), a popular micturition assessment tool, involves placing a mouse in an enclosure lined by filter paper and quantifying the resulting urine spot pattern. The VSA has advantages of being inexpensive and non-invasive, but some investigators challenge its ability to distinguish lower urinary tract function from behavioral voiding. A consensus group of investigators...
Source: Am J Physiol Renal P... - August 29, 2018 Category: Urology & Nephrology Authors: Hill WG, Zeidel ML, Bjorling DE, Vezina CM Tags: Am J Physiol Renal Physiol Source Type: research

Urine Inositol Pentakisphosphate 2-kinase and Changes in Kidney Structure in Early Diabetic Kidney Disease in Type 1 Diabetes.
We examined the association of urine inositol pentakisphosphate 2-kinase (IPP2K) with the presence and progression of diabetic kidney disease (DKD) lesions. Urine IPP2K was measured at baseline by quantitative liquid chromatography mass spectrometry in 215 participants from the Renin-Angiotensin System Study who had type 1 diabetes and were normoalbuminuric and normotensive with normal or increased glomerular filtration rate (GFR). Urine IPP2K was detectable in 166 participants. Participants with IPP2K below the limit of quantification (LOQ) were assigned concentrations of LOQ/√2. All concentrations were then standar...
Source: Am J Physiol Renal P... - August 22, 2018 Category: Urology & Nephrology Authors: Looker HC, Merchant ML, Rane MJ, Nelson RG, Kimmel PL, Rovin BH, Klein JB, Mauer M, Consortium CB Tags: Am J Physiol Renal Physiol Source Type: research

Down-regulation of microRNA-429 contributes to angiotensin II-induced profibrotic effect in rat kidney.
Abstract MicroRNA (miR) 429 has been shown to inhibit epithelial-to-mesenchymal transition (EMT) in cancer cells. However, the role of miR429 in EMT in non-cancer cells has not been defined, especially in the kidneys. The present study determined whether miR429 participated in angiotensin (ANG) II-induced EMT and fibrogenesis in renal cells. In NRK-52E cells, a rat proximal tubular cell line, incubation of ANG II (10-9 M) for 24 h significantly reduced the level of miR429 by 60%, and meanwhile increased the protein levels of mesenchymal markers α-smooth muscle actin and fibroblast-specific protein-1 by 3 fol...
Source: Am J Physiol Renal P... - August 22, 2018 Category: Urology & Nephrology Authors: Wang Z, Zhu Q, Wang W, Hu J, Li PL, Yi F, Li N Tags: Am J Physiol Renal Physiol Source Type: research

Electrical Stimulation of the Pudendal Nerve Promotes Neuroregeneration and Functional Recovery from Stress Urinary Incontinence in a Rat Model.
Abstract The pudendal nerve can be injured during vaginal delivery of children and slowed pudendal nerve regeneration has been correlated with development of stress urinary incontinence (SUI). Simultaneous injury to the pudendal nerve and its target muscle, the external urethral sphincter (EUS), during delivery likely leads to slowed neuroregeneration. The goal of this study was to determine if repeat electrical stimulation of the pudendal nerve improves SUI recovery and promotes neuroregeneration in a dual muscle and nerve injury rat model of SUI. Rats received electrical stimulation or sham stimulation of the pu...
Source: Am J Physiol Renal P... - August 22, 2018 Category: Urology & Nephrology Authors: Jiang HH, Song QX, Gill BC, Balog BM, Juarez R, Cruz Y, Damaser MS Tags: Am J Physiol Renal Physiol Source Type: research

Deletion of the Formin, Diaph1, Protects from Structural and Functional Abnormalities in the Murine Diabetic Kidney.
Abstract Diaphanous 1 (DIAPH1), a member of the formin family, binds to the cytoplasmic domain of the receptor for advanced glycation end products (RAGE) and is required for RAGE signal transduction. Experiments employing genetic over-expression or deletion of Ager (the gene encoding RAGE) or its pharmacological antagonism, implicate RAGE in the pathogenesis of diabetes-associated nephropathy. We hypothesized that DIAPH1 contributes to pathological and functional derangements in the kidneys of diabetic mice. Here, we show that DIAPH1 is expressed in the human and murine diabetic kidney, at least in part in the tub...
Source: Am J Physiol Renal P... - August 22, 2018 Category: Urology & Nephrology Authors: Manigrasso MB, Friedman RA, Ramasamy R, D'Agati VD, Schmidt AM Tags: Am J Physiol Renal Physiol Source Type: research

Electrically stimulated acupuncture increases renal blood flow through exosomes-carried miR-181.
This study provides important new insights about the mechanism(s) by which acupuncture may regulation of muscle-organ cross talk through exosome-derived microRNA. PMID: 30132347 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 22, 2018 Category: Urology & Nephrology Authors: Su Z, Yuan Y, Yu M, Liu Y, Klein JD, Wang XH Tags: Am J Physiol Renal Physiol Source Type: research

Multiphoton imaging reveals axial differences in metabolic auto-fluorescence signals along the kidney proximal tubule.
Abstract Kidney proximal tubules (PTs) are densely packed with mitochondria, and defects in mitochondrial function are implicated in many kidney diseases. However, little is known about intrinsic mitochondrial function within PT cells. Here, using intravital multiphoton microscopy and live slices of mouse kidney cortex, we show that auto-fluorescence signals provide important functional readouts of redox state and substrate metabolism, and that there are striking axial differences in signals along the PT. Mitochondrial NAD(P)H intensity was similar in both S1 and S2 PT segments, and was sensitive to changes in res...
Source: Am J Physiol Renal P... - August 22, 2018 Category: Urology & Nephrology Authors: Bugarski M, Martins J, Haenni D, Hall AM Tags: Am J Physiol Renal Physiol Source Type: research

Absence of renal hypoxia in the subacute phase of severe renal ischemia reperfusion injury.
Abstract Tissue hypoxia has been proposed as an important event in renal ischemia reperfusion injury (IRI) particularly during the period of ischemia and in the immediate hours following reperfusion. However, little is known about renal oxygenation during the subacute phase of IRI. We employed four different methods to assess the temporal and spatial changes in tissue oxygenation during the subacute phase (24 h and 5 days after reperfusion) of a severe form of renal IRI in rats. We hypothesized that the kidney is hypoxic 24 h and 5 days after an hour of bilateral renal ischemia, driven by a disturbed balance betwe...
Source: Am J Physiol Renal P... - August 15, 2018 Category: Urology & Nephrology Authors: Ow CPC, Ngo JP, Ullah MM, Barsha G, Meex RCR, Watt MJ, Hilliard LM, Koeners MP, Evans RG Tags: Am J Physiol Renal Physiol Source Type: research

MAGI-2 and scaffold proteins in glomerulopathy.
Abstract In many cells and tissues including the glomerular filtration barrier (GFB), scaffold proteins are critical in optimizing signal transduction by enhancing structural stability and functionality of their ligands. Recently, mutations in scaffold protein Membrane-Associated Guanylate Kinase Inverted 2 (MAGI-2) encoding gene were identified among the etiology of steroid-resistant nephrotic syndrome (SRNS). MAGI-2 interacts with core proteins of multiple pathways such as TGF-β signaling, planar cell polarity pathway, and Wnt/β-catenin signaling in podocyte and slit diaphragm. Through the interaction ...
Source: Am J Physiol Renal P... - August 15, 2018 Category: Urology & Nephrology Authors: Empitu MA, Kadariswantiningsih IN, Aizawa M, Asanuma K Tags: Am J Physiol Renal Physiol Source Type: research

GLP-1 Receptor Agonists in Diabetic Kidney Disease: from the Patient-Side to the Bench-Side.
Abstract Diabetic kidney disease (DKD), one of the most common and severe microvascular complications of diabetes, is the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Since the development of renin-angiotensin system inhibition nearly three decades ago, no new therapeutic agents have received regulatory approval for treatment of DKD. Glucagon like peptide-1 (GLP-1) receptor agonists, a class of newer anti-hyperglycemic agents, have shown promise for prevention of DKD onset and progression. This perspective summarizes clinical and experimental observations to give insight into bio...
Source: Am J Physiol Renal P... - August 15, 2018 Category: Urology & Nephrology Authors: Dieter BP, Alicic RZ, Tuttle KR Tags: Am J Physiol Renal Physiol Source Type: research

Kidney Injury Molecule-1 Identifies Antemortem Injury in Postmortem Adult and Fetal Kidney.
Abstract There is currently no technique to unambiguously diagnose antemortem kidney injury on postmortem examination since postmortem tissue damage and autolysis are common. We assessed the ability to detect kidney injury molecule-1 (KIM-1) expression in adult and fetal kidneys examined at autopsy. In adult kidneys (n=52 subjects), we found that the intensity of KIM-1 staining significantly correlated with the antemortem level of serum creatinine, and this was independent of the extent of tissue autolysis. Kidneys from a total of 52 fetal/neonatal subjects, 30 stillborns and 22 liveborns, were assessed for KIM-1 ...
Source: Am J Physiol Renal P... - August 15, 2018 Category: Urology & Nephrology Authors: Yin W, Zhang PL, Macknis J, Lin F, Bonventre JV Tags: Am J Physiol Renal Physiol Source Type: research

Vesicles bearing gifts: the functional importance of micro-rna transfer in extracellular vesicles in chronic kidney disease.
VESICLES BEARING GIFTS: THE FUNCTIONAL IMPORTANCE OF MICRO-RNA TRANSFER IN EXTRACELLULAR VESICLES IN CHRONIC KIDNEY DISEASE. Am J Physiol Renal Physiol. 2018 Aug 15;: Authors: Abbasian N, Herbert K, Pawluczyk I, Burton J, Bevington A Abstract Extracellular vesicles (EVs), including microparticles (MPs) and exosomes (EXOs), are derived from a wide range of mammalian cells including blood platelets, endothelial cells, and kidney cells and can be detected in body fluids including blood and urine. While EVs are well established as diagnostic markers under pathophysiological and stress conditions, there is...
Source: Am J Physiol Renal P... - August 15, 2018 Category: Urology & Nephrology Authors: Abbasian N, Herbert K, Pawluczyk I, Burton J, Bevington A Tags: Am J Physiol Renal Physiol Source Type: research

Superoxide via Sp3 mechanism increases renal renin activity, renal AT1 receptor function and blood pressure in rats.
Abstract We tested a hypothesis that superoxide, by inducing Sp3, increases renal renin activity, renal AT1 receptor (AT1R) function and blood pressure (BP) in rats. Group 1 rats were treated with vehicle, saline. Group 2 rats were treated with superoxide dismutase (SOD) inhibitor diethylthiocarbamate (DETC). Group 3 rats were treated with DETC and an SOD mimetic, tempol. Group 4 rats were treated with tempol only. All 4 groups of rats were treated for 2 weeks, anesthetized and BP recorded. Thereafter, diuresis and natriuresis in response to AT1R blocker candesartan were determined. Compared to vehicle-rats, BP in...
Source: Am J Physiol Renal P... - August 15, 2018 Category: Urology & Nephrology Authors: Saleem M, Wang X, Pokkunuri I, Asghar M Tags: Am J Physiol Renal Physiol Source Type: research

Why until Just Now? Undiscovered Uniqueness of the Human Glomerulus!
PMID: 30110573 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 15, 2018 Category: Urology & Nephrology Authors: Navar LG, Richfield O Tags: Am J Physiol Renal Physiol Source Type: research

Am J Physiol Renal Physiol; +18 new citations
18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: Am J Physiol Renal Physiol These pubmed results were generated on 2018/08/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites. (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 11, 2018 Category: Urology & Nephrology Tags: Report Source Type: research

Flow Resistance along the Rat Renal Tubule.
Abstract The Reynolds number in the renal tubule is extremely low, consistent with laminar flow. Consequently, luminal flow can be described by the Hagen-Poiseuille laminar flow equation. This equation calculates the volumetric flow rate from values of the axial pressure gradient and flow resistance, which is dependent on the length and diameter of each renal tubule segment. Our goal was to calculate the pressure drop along each segment of the renal tubule and determine the points of highest resistance. When the Hagen-Poiseuille equation was used for rat superficial nephrons based on known flow rates, tubule lengt...
Source: Am J Physiol Renal P... - August 8, 2018 Category: Urology & Nephrology Authors: Gilmer GG, Deshpande V, Chou CL, Knepper MA Tags: Am J Physiol Renal Physiol Source Type: research

Regulation of the Renal NaCl Cotransporter by the WNK/SPAK Pathway. Lessons Learned from Genetically Altered Animals.
We present a review of all genetically altered mice that have been used to translate most of the proposals made from in vitro experiments into in vivo observations that have helped to elucidate the model at the physiological level. Many questions have been resolved, but some others will require further models to be constructed. In addition, unexpected observations in mice have raised new questions and identified regulatory pathways that were previously unknown. PMID: 30089030 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 8, 2018 Category: Urology & Nephrology Authors: Ostrosky-Frid M, Castañeda-Bueno M, Gamba G Tags: Am J Physiol Renal Physiol Source Type: research

Development of stress-induced bladder insufficiency requires functional TRPV1 channels.
Abstract Social stress causes profound urinary bladder dysfunction in children that often continues into adulthood. We discovered that the intensity and duration of social stress influences whether bladder dysfunction presents as overactivity or underactivity. The transient receptor potential vanilloid type 1 (TRPV1) channel is integral in causing stress-induced bladder overactivity by increasing bladder sensory outflow, but little is known about the development of stress-induced bladder underactivity. We sought to determine if TRPV1 channels are involved in bladder underactivity caused by stress. Voiding function...
Source: Am J Physiol Renal P... - August 8, 2018 Category: Urology & Nephrology Authors: Tykocki NR, Heppner TJ, Erikson CS, van Batavia JP, Vizzard MA, Nelson MT, Mingin GC Tags: Am J Physiol Renal Physiol Source Type: research

Intraluminal Pressure Triggers Myogenic Response via Activation of Calcium Spark and Calcium-Activated Chloride Channel in Rat Renal Afferent Arteriole.
Abstract Myogenic contraction of renal arterioles is an important regulatory mechanism for renal blood flow autoregulation. We have previously demonstrated that integrin-mediated mechanical force increases the occurrence of Ca2+ sparks in freshly isolated renal vascular smooth muscle cells (VSMCs). To further test whether generation of Ca2+ sparks is a downstream signal of mechanotransduction in pressure induced myogenic constriction, the relationship between Ca2+ spark frequency and transmural perfusion pressure was investigated in intact VSMCs of pressurized rat afferent arterioles. Spontaneous Ca2+ sparks were ...
Source: Am J Physiol Renal P... - August 8, 2018 Category: Urology & Nephrology Authors: Yip KP, Balasubramanian L, Kan C, Wang L, Liu R, Ribeiro-Silva L, Sham JSK Tags: Am J Physiol Renal Physiol Source Type: research

Section-specific expression of acid-base and ammonia transporters in the kidney tubules of the goldfish Carassius auratus and their responses to feeding.
Abstract In teleost fishes, renal contributions to acid-base and ammonia regulation are often neglected compared to the gills. In goldfish, increased renal acid-excretion in response to feeding was indicated by increased urine ammonia and inorganic phosphate concentrations and decreased urine pH. By micro-dissecting the kidney tubules and performing quantitative real-time PCR and/or immunohistochemistry, we profiled the section-specific expression of glutamate dehydrogenase (GDH), glutamine synthetase (GS), Na+/H+-exchanger 3 (NHE3), carbonic anhydrase II (CAIIa), V-H+-ATPase subunit 1b, Cl-/HCO3--exchanger 1 (AE1...
Source: Am J Physiol Renal P... - August 8, 2018 Category: Urology & Nephrology Authors: Fehsenfeld S, Wood CM Tags: Am J Physiol Renal Physiol Source Type: research

Early life voiding dysfunction leads to lower urinary tract dysfunction through alteration of muscarinic and purinergic signaling in the bladder.
Abstract Lower urinary tract dysfunction (LUTD) is a common problem in children and constitutes up to 40 percent of pediatric urology clinic visits. Improved diagnosis and interventions have been leading to better outcomes in many patients, while some children are left untreated or do not respond to the treatment successfully. In addition, many of these patients are lost by the pediatric urologists during their teenage years, and the outcome in later life largely remains unidentified. Studies suggest childhood LUTD is associated with subsequent adult urinary tract symptoms. However, whether and how early life LUTD...
Source: Am J Physiol Renal P... - August 8, 2018 Category: Urology & Nephrology Authors: Iguchi N, Malykhina AP, Wilcox DT Tags: Am J Physiol Renal Physiol Source Type: research

LRRK2 Deficiency Impairs trans-Golgi to Lysosome Trafficking and Endocytic Cargo Degradation in Human Renal Proximal Tubule Epithelial Cells.
Abstract Defects in vesicular trafficking underlie a wide variety of human diseases. Genetic disruption of leucine-rich repeat kinase 2 (LRRK2) in rodents results in epithelial vesicular trafficking errors that can also be induced by treatment of animals with LRRK2 kinase inhibitors. Here we demonstrate that defects in human renal cells lacking LRRK2 phenocopy those seen in the kidneys of Lrrk2 knockout mice, characterized by accumulation of intracellular waste vesicles and fragmentation of the Golgi apparatus. This phenotype can be recapitulated by knockdown of N-ethylmaleimide sensitive factor (NSF), which physi...
Source: Am J Physiol Renal P... - August 8, 2018 Category: Urology & Nephrology Authors: Lanning NJ, VanOpstall C, Goodall ML, MacKeigan JP, Looyenga BD Tags: Am J Physiol Renal Physiol Source Type: research

Renal Functional Reserve Capacity before and after Living Kidney Donation.
In conclusion, RFRdopa is a predictor of short-term GFR after living kidney donation, but not of long-term kidney function. Therefore, measurement of the RFRdopa is not a useful tool for donor screening. Studies investigating long-term renal adaptation are warranted to study the effects of living kidney donation and improve donor screening. PMID: 30089036 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 8, 2018 Category: Urology & Nephrology Authors: van Londen M, Kasper N, Hessels NR, Messchendorp AL, Bakker SJL, Sanders JF, Berger SP, de Borst MH, Navis G Tags: Am J Physiol Renal Physiol Source Type: research

Multi-Parametric MRI Detects Longitudinal Evolution of Folic Acid-Induced Nephropathy in Mice.
In conclusion, multi-parametric MRI captured the longitudinal progression in kidney damage evolving within the first month after treatment with folic acid, and may provide a useful tool for assessment of therapeutic strategies. PMID: 30089037 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 8, 2018 Category: Urology & Nephrology Authors: Jiang K, Ponzo TA, Tang H, Mishra PK, Macura SI, Lerman LO Tags: Am J Physiol Renal Physiol Source Type: research

Randall's Plaque in Stone Formers Originates in Ascending Thin Limbs.
Abstract Randall's plaque, an attachment site over which calcium oxalate stones form, begins in the basement membranes of the thin limbs of the loop of Henle. The mechanism of its formation is unknown. Possibly, enhanced delivery of calcium out of proximal tubule, found in many stone formers, increases reabsorption of calcium from thick ascending limb into the interstitium around descending vasa recta, that convey that calcium into the deep medulla, and raises supersaturations near thin limbs ('vas washdown'). If true, plaque should form preferentially on ascending thin limbs, which do not reabsorb water. We stain...
Source: Am J Physiol Renal P... - August 1, 2018 Category: Urology & Nephrology Authors: Evan AP, Coe FL, Lingeman JE, Bledsoe SB, Worcester EM Tags: Am J Physiol Renal Physiol Source Type: research

Antihyperglycemic Agents as Novel Natriuretic Therapies in Diabetic Kidney Disease.
onzález JP Abstract While SGLT2 inhibitors have been use for the routine management of type 2 diabetes for several years, it is perhaps their natriuretic effects that are most important clinically. This natriuresis activates tubuloglomerular feedback, resulting in reduced glomerular hypertension and proteinuria, leading to renal protective effects in the EMPA-REG OUTCOME and CANVAS Program trials. In the cardiovascular system, it is likely that plasma volume contraction due to natriuresis in response to SGLT2 inhibition is at least in part responsible for the reduction in the risk of heart failure observed ...
Source: Am J Physiol Renal P... - August 1, 2018 Category: Urology & Nephrology Authors: León Jiménez D, Cherney DZI, Bjornstad P, Castilla Guerra L, Miramontes González JP Tags: Am J Physiol Renal Physiol Source Type: research

Nephron specific knockin of the PIKfyve binding deficient Vac14L156R mutant results in albuminuria and mesangial expansion.
H, Weide T Abstract Intracellular trafficking processes play a key role for the establishment and maintenance of membrane surfaces in renal epithelia. Therefore, dysfunctions of these trafficking processes could be key events and important determinants in the onset and progression of diseases. The presence of cellular vacuoles - observed in many histologic analyses of renal diseases - is a macroscopic hint for disturbed intracellular trafficking processes. However, how vacuoles develop and which intracellular pathways are directly affected remains largely unknown. Previous studies showed that in some cases vacuol...
Source: Am J Physiol Renal P... - August 1, 2018 Category: Urology & Nephrology Authors: Michgehl U, Skryabin BV, Bayraktar S, Vollenbröker B, Ciarimboli G, Heitplatz B, Van Marck V, Gröne HJ, Pavenstädt H, Weide T Tags: Am J Physiol Renal Physiol Source Type: research

Acid-base regulation in the renal proximal tubules: using novel pH sensors to maintain homeostasis.
Abstract The kidneys play a critical role in precisely regulating the composition of the plasma to maintain homeostasis. To achieve this, the kidneys must be able to accurately determine or "sense" the concentration of a wide variety of substances, and to make adjustments accordingly. Kidneys face a key challenge in the arena of pH balance, as there is a particularly narrow range over which plasma pH varies in a healthy subject (7.35-7.45), and this pH must constantly be protected against a variety of onslaughts (changes in diet, activity, and even elevation). The proximal tubule, the first segment to co...
Source: Am J Physiol Renal P... - August 1, 2018 Category: Urology & Nephrology Authors: Rajkumar P, Pluznick JL Tags: Am J Physiol Renal Physiol Source Type: research

Plasma and Urinary p21: Potential Biomarkers of AKI and Renal Aging.
CONCLUSIONS: i) During AKI, renal p21 levels can be gauged by plasma and urine p21 assay, and thus, serve as a potentially useful AKI/CCA biomarker; ii) AKI can activate p21 in extra-renal organs; and iii) plasma p21 levels may provide an index of the renal/systemic aging process. PMID: 30066587 [PubMed - as supplied by publisher] (Source: Am J Physiol Renal P...)
Source: Am J Physiol Renal P... - August 1, 2018 Category: Urology & Nephrology Authors: Johnson AC, Zager RA Tags: Am J Physiol Renal Physiol Source Type: research

Mini review: Single molecule labeling for studying trafficking of renal transporters.
Abstract The ability to detect and track single molecules presents the advantage of visualizing the complex behavior of individual proteins with a time and space resolution that would otherwise be lost with traditional labeling and biochemical techniques. This is achieved by a combination of single molecule labeling and high-resolution microscopy. In the last 10 years, single molecule labeling of membrane proteins has contributed enormously to our understanding of their function, behavior and trafficking in polarized epithelium. Surprisingly, application of these techniques to study transporters in renal epitheliu...
Source: Am J Physiol Renal P... - July 25, 2018 Category: Urology & Nephrology Authors: Jaykumar AB, Caceres PS, Ortiz PA Tags: Am J Physiol Renal Physiol Source Type: research

Doxycycline attenuates cisplatin-induced acute kidney injury through pleiotropic effects.
Abstract Cisplatin (CDDP) is a widely-used chemotherapeutic drug for solid tumors, but its nephrotoxicity is a major dose-limiting factor. Doxycycline (Dox) is a tetracycline antibiotic that has been commonly used in a variety of infections. Dox has been shown to possess several other properties, including anti-tumor, anti-inflammatory, anti-oxidative, and matrix metalloproteinase (MMP)-inhibiting actions. We therefore investigated whether Dox exerts renoprotective effects in CDDP-induced acute kidney injury (AKI). Twelve-week-old male C57BL/6J mice were divided into the following groups: 1) Control, 2) Dox (2 mg/...
Source: Am J Physiol Renal P... - July 25, 2018 Category: Urology & Nephrology Authors: Nakagawa T, Kakizoe Y, Iwata Y, Miyasato Y, Mizumoto T, Adachi M, Izumi Y, Kuwabara T, Suenaga N, Narita Y, Jono H, Saito H, Kitamura K, Mukoyama M Tags: Am J Physiol Renal Physiol Source Type: research

Novel haemodynamic structures in the human glomerulus.
NOVEL HAEMODYNAMIC STRUCTURES IN THE HUMAN GLOMERULUS. Am J Physiol Renal Physiol. 2018 Jun 20;: Authors: Neal CR, Arkill K, Bell JS, Betteridge KB, Bates DO, Winlove CP, Salmon AH, Harper SJ Abstract To investigate human glomerular structure under conditions of physiological perfusion we have analysed fresh and perfusion fixed normal human glomeruli at physiological hydrostatic and oncotic pressures using serial resin section reconstruction, confocal, multiphoton and electron microscope imaging. Afferent and efferent arterioles (21.5{plus minus}1.2µm and 15.9{plus minus}1.2µm diameter), r...
Source: Am J Physiol Renal P... - June 20, 2018 Category: Urology & Nephrology Authors: Neal CR, Arkill K, Bell JS, Betteridge KB, Bates DO, Winlove CP, Salmon AH, Harper SJ Tags: Am J Physiol Renal Physiol Source Type: research

Regulation of Renal Na Transporters in Response to Dietary K.
Abstract Changes in the expression of Na transport proteins were measured in the kidneys of mice with increased dietary K intake for 1 week. The epithelial Na channel (ENaC) was upregulated, with enhanced expression of full-length and cleaved forms of αENaC and cleaved γENaC. At the same time, the amount of the NaCl cotransporter (NCC) and its phosphorylated form decreased by ~50% and ~80% respectively. The expression of the phosphorylated form of the Na-K-2Cl cotransporter NKCC2 also decreased, despite an increase in overall protein content. The effect was stronger in males (80%) than in females (40%)...
Source: Am J Physiol Renal P... - June 20, 2018 Category: Urology & Nephrology Authors: Yang L, Xu S, Guo X, Uchida S, Weinstein AM, Wang T, Palmer LG Tags: Am J Physiol Renal Physiol Source Type: research

Physiological functions of Ferroportin in the regulation of renal iron recycling and ischemic acute kidney injury.
Abstract Renal iron recycling preserves the filtered iron from urinary excretion. However, it remains debated whether ferroportin (FPN), the solely known iron exporter, is functionally involved in renal iron recycling, and whether renal iron recycling is required for systemic iron homeostasis. We deleted FPN in the whole nephrons using a Nestin-Cre and in the distal nephrons and collecting ducts using a Ksp-Cre, and investigated its impacts on renal iron recycling and systemic iron homeostasis. FPN deletion by Nestin-Cre but not by Ksp-Cre caused excess iron retention and increased ferritin heavy chain (FTH1) spec...
Source: Am J Physiol Renal P... - June 20, 2018 Category: Urology & Nephrology Authors: Wang X, Zheng X, Zhang J, Zhao S, Wang Z, Wang F, Shang W, Barasch J, Qiu A Tags: Am J Physiol Renal Physiol Source Type: research

WNK-SPAK/OSR1 signaling: lessons learned from an insect renal epithelium.
Abstract WNK (With No Lysine (K)) kinases regulate renal epithelial ion transport to maintain homeostasis of electrolyte concentrations, extracellular volume and blood pressure. The SLC12 cation-chloride cotransporters, including the sodium-potassium-2-chloride (NKCC) and sodium-chloride (NCC) cotransporters, are targets of WNK regulation via the intermediary kinases SPAK (Ste20-related proline/alanine-rich kinase) and OSR1 (oxidative stress response). The pathway is activated by low dietary potassium intake, resulting in increased phosphorylation and activity of NCC. Chloride regulates WNK kinases in vitro by bin...
Source: Am J Physiol Renal P... - June 20, 2018 Category: Urology & Nephrology Authors: Rodan AR Tags: Am J Physiol Renal Physiol Source Type: research

The protective role of Trpc6 knockout in the progression of diabetic kidney disease.
Abstract Diabetic kidney disease (DKD) is a chronic kidney pathology that leads to end stage renal disease. Previous studies from our laboratory indicate that there is an association between the development of DKD and the TRPC6 channel. Trpc6 expression and activity was increased in the streptozotocin (STZ)-treated Dahl Salt-sensitive (SS) rat, an established model of type 1 diabetes. Here, using a Trpc6 knock-out created on the SS rat background (SSTRPC6-/-), we test the hypothesis that the absence of Trpc6 will protect podocytes and kidney function during the development of DKD. Four groups of animals - control ...
Source: Am J Physiol Renal P... - June 20, 2018 Category: Urology & Nephrology Authors: Spires D, Ilatovskaya DV, Levchenko V, North PE, Geurts AM, Palygin O, Staruschenko A Tags: Am J Physiol Renal Physiol Source Type: research

Intrarenal ghrelin receptor inhibition ameliorates angiotensin ii-dependent hypertension in rats.
INTRARENAL GHRELIN RECEPTOR INHIBITION AMELIORATES ANGIOTENSIN II-DEPENDENT HYPERTENSION IN RATS. Am J Physiol Renal Physiol. 2018 Jun 20;: Authors: Kemp BA, Howell NL, Padia SH Abstract 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 osm...
Source: Am J Physiol Renal P... - June 20, 2018 Category: Urology & Nephrology Authors: Kemp BA, Howell NL, Padia SH Tags: Am J Physiol Renal Physiol Source Type: research

Intrarenal Toll-like receptor 4 and Toll-like receptor 2 expression correlates with injury in anti-neutrophil cytoplasmic antibody associated vasculitis.
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. Glomerular TLR4 expression correlated with glomerular segmental necrosis and cellular crescents, with TLR2 expression correlating with glomerular segmental necrosis. The extent and intensity of glomerular and tubulointerstitial TLR4 expression, and the intensity of glomerular TLR2 expression inversel...
Source: Am J Physiol Renal P... - June 20, 2018 Category: Urology & Nephrology Authors: O'Sullivan KM, Ford SL, Longano A, Kitching AR, Holdsworth SR Tags: Am J Physiol Renal Physiol Source Type: research