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American Journal of Physiology. Renal Physiology

Ning Wei, Michelle L Gumz, Anita T Layton
Major renal functions such as renal blood flow, glomerular filtration rate, and urinary excretion are known to exhibit circadian oscillations. However, the underlying mechanisms that govern these variations have yet to be fully elucidated. To better understand the impact of the circadian clock on renal solute and water transport, we have developed a computational model of the renal circadian clock, and coupled that model to an epithelial transport model of the proximal convoluted cell of the rat kidney. The activity of the Na$^+$-H$^+$ exchanger 3 (NHE3) is assumed to be regulated by changes in transcription of the NHE3 mRNA due to regulation by circadian clock proteins...
March 14, 2018: American Journal of Physiology. Renal Physiology
Xiaoyan Wen, Liyan Cui, Seth Morrisroe, Donald Maberry, David R Emlet, Simon C Watkins, Neil A Hukriede, John A Kellum
Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish (Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for sepsis-associated AKI research. We introduced Edwardsiella tarda (E.tarda) to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality...
March 14, 2018: American Journal of Physiology. Renal Physiology
Katy Billot, Charlène Coquil, Benoit Villiers, Béatrice Josselin-Foll, Nathalie Desban, Claire Delehouze, Nassima Oumata, Yannick Le Meur, Alessandra Boletta, Thomas Weimbs, Melanie Grosch, Ralph Witzgall, Sophie Saunier, Evelyne Fischer, Marco Pontoglio, Alain Fautrel, Michal Mrug, Darren Paul Wallace, Pamela V Tran, Marie Trudel, Nikolay O Bukanov, Oxana Ibraghimov-Beskrovnaya, Laurent Meijer
Following the discovery of (R)-roscovitine's beneficial effects in three polycystic kidney disease (PKD) mouse models, cyclin-dependent kinases (CDKs) inhibitors are investigated as potential treatments. We have used various affinity chromatography approaches to identify the molecular targets of roscovitine and its more potent analogue (S)-CR8 in human and murine polycystic kidneys. These methods revealed casein kinases 1 (CK1) as additional targets of the two drugs. CK1ε expression at the mRNA and protein levels is enhanced in polycystic kidneys of 11 different PKD mouse models, as well as in human polycystic kidneys...
March 14, 2018: American Journal of Physiology. Renal Physiology
James Gilbert Atherton, David S Hains, John J Bissler, Bradford D Pendley, Erno Lindner
Current dialysis dosing calculations provide an incomplete assessment of blood purification. They do not include clearances of protein-bound uremic toxins like polyamines, p-cresol sulfate, and indoxyl sulfate, relying solely on the clearance of urea as a surrogate for all molecules accumulating in patients with end stage renal disease (ESRD). Protein-bound uremic toxins clear differently in dialysis but also during normal renal function. The kidney clears protein bound toxins via the process of secretion, while it clears urea through filtration...
March 14, 2018: American Journal of Physiology. Renal Physiology
Ying Jing, Ming Wu, Di Zhang, Dongping Chen, Ming Yang, Shuqin Mei, Liangliang He, Junhui Gu, Na Qi, Lili Fu, Lin Li, Changlin Mei
OBJECTIVES: The aim of our current study was to investigate the long-term effect and the mechanism of triptolide in an adult non-orthologous rat model of polycystic kidney disease (PKD), and study the effect of triptolide on the mitogenic JAK2/STAT3 pathway.. METHODS: Male wild type (WT+/+) and Cy/+ cystic Han:SPRD rats were treated with vehicle or triptolide from week 44 weeks to week 16 weeks of age. Rats were sacrificed at 16 weeks of age 16 for the blood, urine and organ collection...
March 7, 2018: American Journal of Physiology. Renal Physiology
David J Friedman, Seth L Alper
No abstract text is available yet for this article.
March 7, 2018: American Journal of Physiology. Renal Physiology
Tracy Bell, Magali Araujo, Zaiming Luo, James Tomlinson, James Leiper, William J Welch, Christopher S Wilcox
BACKGROUND: Nitric oxide prevents hypertension yet paradoxically reduces proximal tubule Na+ reabsorption. Nitric oxide synthase is inhibited by asymmetric dimethylarginine (ADMA) that is metabolized by dimethylarginine dimethylaminohydrolase (DDAH) whose type 1 isoform is expressed abundantly in the PT. HYPOTHESIS: That ADMA generated by DDAH-1 fluid reabsorbtion (Jv) by the proximal tubule. METHODS: S2 segments of the PT were perfused in vivo to assess Jv...
March 7, 2018: American Journal of Physiology. Renal Physiology
Erin E Olsan, Jonathan D West, Jacob A Torres, Nicholas Doerr, Thomas Weimbs
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a life-threatening, highly prevalent monogenic disease caused by mutations in polycystin-1 (PC1) in 85% of patients. We have previously identified a C-terminal cleavage fragment of PC1, PC1-p30, that interacts with the transcription factor STAT6 to promote transcription. STAT6 is aberrantly active in PKD mouse models and human ADPKD, and genetic removal or pharmacological inhibition of STAT6 attenuates disease progression. High levels of interleukin-13 (IL13), a STAT6 activating cytokine, are found in the cyst fluid of PKD mouse models and increased IL13 receptors in ADPKD patient tissue suggesting that a positive feedback loop between IL13 and STAT6 is activated in cystic epithelial cells and contributes to disease progression...
March 7, 2018: American Journal of Physiology. Renal Physiology
Christian Patry, Christian Betzen, Farnoosh Fathalizadeh, Alexander Fichtner, Jens H Westhoff, Thomas Fleming, Volker Eckstein, Tom Bruckner, Martina Bielaszewska, Helge Karch, Georg F Hoffmann, Burkhard Tönshoff, Neysan Rafat
Endothelial injury with consecutive microangiopathy and endothelial dysfunction plays a central role in the pathogenesis of the post-enteropathic hemolytic uremic syndrome (D+HUS). To identify new treatment strategies, we examined the regenerative potential of endothelial progenitor cells (EPC) in an in vitro model of Shiga toxin (Stx) 2a-induced glomerular endothelial injury present in D+HUS and the mechanisms of EPC-triggered endothelial regeneration. We simulated the pro-inflammatory milieu present in D+HUS by priming human renal glomerular endothelial cells (HRGEC) with Tumor Necrosis Factor (TNF)-α prior to stimulation with Stx2a...
March 7, 2018: American Journal of Physiology. Renal Physiology
Jie Zhang, Shan Jiang, Jin Wei, Kay-Pong Yip, Lei Wang, En Yin Lai, Ruisheng Liu
Glomerular hyperfiltration often occurs during the early stage of diabetes. An acute glucose infusion increases glomerular filtration rate (GFR). The involvement of tubuloglomerular feedback response and direct effect of glucose on the afferent arterioles (Af-Arts) have been suggested. However, the signaling pathways to trigger Af-Art dilatation have not been fully identified. Therefore, in the present study we tested our hypothesis that an increase of glucose concentration enhances endothelial nitric oxide synthesis (NOS3) activity and dilates the Af-Arts via glucose transporter 1 (GLUT1) using isolated mouse Af-Arts with perfusion...
March 7, 2018: American Journal of Physiology. Renal Physiology
Barbara Toffoli, Cristina Zennaro, Carine Winkler, Greta Maria Paola Giordano Attianese, Stella Bernardi, Michele Carraro, Federica Gilardi, Beatrice Desvergne
Different complex mechanisms control the morphology of podocyte foot processes and their interactions with the underlying basement membrane. Injuries to this system often cause glomerular dysfunction and albuminuria. The present study aimed at identifying early markers of glomerular damage in diabetic nephropathy. For this purpose, we performed a microarray analysis on kidneys of 3-week-old PPARγ null and AZIP/F1 mice, which are two models of diabetic nephropathy due to lipodystrophy. This was followed by functional annotation of the enriched clusters of genes...
February 28, 2018: American Journal of Physiology. Renal Physiology
Bo Wu, Xue Gong, William A Kennedy, James D Brooks
Renal obstruction is a common cause of renal failure in adults and children and is suspected when hydronephrosis is detected on imaging. Since not all cases of hydronephrosis are associated with renal damage, biomarkers are needed to guide intervention to relieve obstruction. We performed gene expression profiling on the kidneys from adult mice over a detailed time course after obstruction and compared these data to a neonatal model of bilateral high grade obstruction induced by conditional deletion of the calcineurin ß1 (Cnb1) gene...
February 28, 2018: American Journal of Physiology. Renal Physiology
Julia Dolinina, Anna Rippe, Peter Bentzer, Carl M Öberg
It is well known that proteinuria following urinary tract obstruction is mainly of a tubular nature. Whether there are also changes in glomerular permeability is however unknown. In this study we compared glomerular sieving coefficients (θ) of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 following 120 or 180 min unilateral ureteral obstruction (UUO) in anesthetized Sprague-Dawley rats. Samples were collected from the obstructed kidney at 5, 15 and 30 minutes post-release and analyzed by means of high pressure size-exclusion chromatography (HP-SEC)...
February 21, 2018: American Journal of Physiology. Renal Physiology
Wenbin Yang, Timothy J Searl, Ryan E Yaggie, Anthony J Schaeffer, David J Klumpp
Interstitial cystitis/ bladder pain syndrome (IC/BPS) is a chronic bladder condition associated with pain and voiding dysfunction that is often regarded as a neurogenic cystitis. Patient symptoms are correlated with the presence of urothelial lesions. We previously characterized a murine neurogenic cystitis model that recapitulates mast cell accumulation and urothelial lesions, and these events were dependent upon TNF. To further explore the role of TNF in bladder inflammation and function, we generated a transgenic mouse model with chronic TNF overexpression in urothelium under the control of the uroplakin II (UPII) promoter...
February 21, 2018: American Journal of Physiology. Renal Physiology
Jie Zhang, Jing Cong, Jie Yang, Jesper Skovhus Thomsen, Arne Andreasen, Shi-Jie Chang, Kai-Yue Wang, Ling Gu, Xiao-Yue Zhai
A proper morphogenesis of the renal microvasculature is crucial not only for fulfilling the renal function, but also to slow down the progression of chronic kidney disease in adulthood. However, the current description of the developing microvasculature is incomplete. The present study investigated the morphogenesis and volume densities of the renal microvasculature using computer-assisted tubular tracing, immunohistochemistry for CD34, and unbiased stereology. The earliest glomerular capillaries were observed at the lower cleft of the S-shape nephrons, as simple loops connecting the afferent and efferent arterioles...
February 21, 2018: American Journal of Physiology. Renal Physiology
Alissa A Frame, Richard David Wainford
The prevalence of hypertension rises with age to approximately two out of three adults over the age of 60 in the United States. Although the mechanisms underlying age-related hypertension are incompletely understood, sodium homeostasis is critical to the long-term regulation of blood pressure and there is strong evidence that aging is associated with alterations in renal sodium handling. This mini-review focuses on recent advancements in our understanding of the vascular, neurohumoral, and renal mechanisms that influence sodium homeostasis and promote age-related hypertension...
February 14, 2018: American Journal of Physiology. Renal Physiology
Takahisa Suzuki, Takahiro Shimizu, Joonbeom Kwon, Eiichiro Takaoka, Satoru Yoshikawa, Yasuhiro Sumino, Takeya Kitta, Minoru Miyazato, Hideaki Miyake, Naoki Yoshimura
To clarify the role of serotonin (5-HT) in the prevention of stress urinary incontinence (SUI) during sneezing, we investigated the effect of intraperitoneal application of p-chlorophenylalanine (PCPA; a serotonin synthesis inhibitor) and intravenous application of CP-809101 (a 5-HT 2C agonist) or LP44 (a 5-HT 7 agonist) using female rats, in which the neurally evoked continence reflex during sneezing was examined. Amplitudes of urethral pressure response during sneezing (A-URS), urethral baseline pressure (UBP) at the middle urethra, and sneeze-induced leak point pressure (S-LPP) were measured in normal female adult rats with or without drug administration...
February 14, 2018: American Journal of Physiology. Renal Physiology
Erika Guise, Alejandro R Chade
Renovascular disease (RVD) is prevalent in the elderly, significantly increases cardiovascular risk, and can progressively deteriorate renal function. The loss of renal function in patients with RVD is associated with a progressive dysfunction, damage, and loss of renal microvessels, which pairs with decreased renal bioavailability of vascular endothelial growth factor (VEGF) and a defective vascular repair and proliferation. This association has been the impetus for recent efforts that focused on developing methods to stop the progression of renal injury by protecting the renal microvasculature...
February 14, 2018: American Journal of Physiology. Renal Physiology
Chunli Wang, Ying Chen, Bixia Zheng, Mengshu Zhu, Jia Fan, Juejin Wang, Zhanjun Jia, Songming Huang, Aihua Zhang
Inactivated variants in CLCNKB gene encoding the basolateral chloride channel ClC-Kb cause classic Bartter syndrome characterized by hypokalemic metabolic alkalosis and hyperreninemic hyperaldosteronism. Here we identified two cBS siblings presenting hypokalemia in a Chinese family due to novel compound heterozygous CLCNKB mutations (c.848_850delTCT/c.1755A>G). Compound heterozygosity was confirmed by amplifying and sequencing the patient's genomic DNA. The synonymous mutation c.1755A>G (Thr585Thr) was located at +2bp from the 5' splice donor site in exon 15, further transcript analysis demonstrated that this single nucleotide mutation causes exclusion of exon 15 in the cDNA from the proband and his mother...
February 14, 2018: American Journal of Physiology. Renal Physiology
Emma L Watson, Douglas W Gould, Thomas J Wilkinson, Soteris Xenophontos, Amy L Clarke, Barbara Perez Vogt, João Luís Viana, Alice C Smith
There is a growing consensus that chronic kidney disease (CKD) patients should engage in regular exercise, but there is a lack of formal guidelines. In this report, we determined whether combined aerobic and resistance exercise would elicit superior physiological gains, in particular muscular strength, compared to aerobic training alone in non-dialysis CKD. Non-dialysis CKD patients stage 3b-5 were randomly allocated to aerobic exercise (AE, n=21; 9 males; median age 63years [IQR, 58-71]; median eGFR 24[IQR, 20-30] mL/min/1...
February 7, 2018: American Journal of Physiology. Renal Physiology
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