AJP Renal Physiology (Am J Physiol Ren Physiol)

Publisher: American Physiological Society (1887- ), American Physiological Society

Journal description

The American Journal of Physiology: Renal Physiology publishes original manuscripts on a broad range of subjects relating to the kidney, urinary tract, and their respective cells and vasculature, as well as to the control of body fluid volume and composition. Studies may involve human or animal models, individual cell types, and isolated membrane systems. Authors are encouraged to submit reports on research using a wide range of approaches to the study of function in these systems, such as biochemistry, immunology, genetics, mathematical modeling, molecular biology, and physiological methodologies. Papers on the pathophysiological basis of disease processes of the kidney, urinary tract, and regulation of body fluids are also encouraged.

Current impact factor: 4.42

Impact Factor Rankings

Additional details

5-year impact 0.00
Cited half-life 5.80
Immediacy index 0.99
Eigenfactor 0.05
Article influence 1.34
Website American Journal of Physiology - Renal Physiology website
Other titles American journal of physiology., Renal physiology, Renal physiology, AJP: renal physiology
ISSN 1522-1466
OCLC 40065092
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

American Physiological Society

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
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  • Conditions
    • NIH, Wellcome Trust, HHMI, MRC and BBSRC authors will on their behalf have the Publisher's version/PDF deposited in PubMed Central for release 12 months after publication
    • Publisher's version/PDF cannot be used
  • Classification
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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pregnancy is characterized by plasma volume expansion due to sodium retention, driven by aldosterone. The aldosterone-responsive epithelial Na channel (ENaC) is activated in the kidney in pregnancy. Here, we investigated the aldosterone-responsive sodium chloride co-transporter, NCC, in mid- and late pregnant rats, compared to virgins. We determined abundance of total NCC, phosphorylated NCC (pT53; pS71 and pS89), phosphorylated SPAK (pS373), and phosphorylated OSR1 (pS325) in kidney cortex. We also measured mRNA expression of NCC, and members of SPAK/NCC regulatory kinase network, SGK1, total WNK1, WNK3, and WNK4. Additionally, we performed immunohistochemistry (IHC) for NCC kidneys from virgin and pregnant rats. Total NCC, pNCC, and pSPAK/OSR1 abundance were unchanged in mid-pregnant vs. virgins. In late pregnant vs. virgin, total and pNCC was decreased, however pSPAK/OSR1 was unchanged. We detected no differences in mRNA expression of NCC, SGK1, total WNK1, WNK3, and WNK4. By IHC, NCC was mainly localized to the apical region in virgins and the density in the apical region was reduced in late pregnancy. Therefore, despite high circulating aldosterone levels in pregnancy, the aldosterone-responsive transporter NCC is not increased in total or activated (phosphorylated) abundance, or in apical localization in mid-pregnant rats, and all are reduced in late pregnancy. This contrasts to the mineralocorticoid-mediated activation of ENaC which we have previously reported. Why and how NCC escapes aldosterone activation in pregnancy is not clear, but may relate to regional differences in aldosterone sensitivity the increased potassium intake or other undefined mechanisms. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00147.2015
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    ABSTRACT: We have previously shown that ovariectomy in adult Wistar rats under normal sodium (NS) intake results in an overexpression of total Na+, K+-ATPase α 1subunit (NKA). Upon high sodium (HS) intake ovariectomized (oVx) rats developed a defective NKA phosphorylation, a decrease in sodium excretion, and an increment in mean blood pressure (MBP). Since NKA phosphorylation is modulated by dopamine (DA), the aim of this study was to compare the intracellular response of the renal DA system leading to NKA phosphorylation upon sodium challenge in intact female (IF) and oVx rats. In IF rats HS caused an increase in urinary DA and sodium, in NKA phosphorylation state, in Cytochrome P4504A (CYP4A) expression and in 20-HETE production, while MBP kept normal. Blockade of D1R with the D1-like receptor antagonist SCH23390 in IFHS rats shifted NKA into a more dephosphorylated state, decreased sodium excretion by 50 % and increased MBP. In oVxNS rats, D1R expression was reduced and D3R expression was increased, and under HS intake sodium excretion was lower and MBP higher than in IFHS rats (both p<0.05), NKA was more dephosphorylated than in IFHS and CYP4A expression or 20-HETE production did not change. Blockade of D1R in oVxHS rats changed neither NKA phosphorylation state nor sodium excretion or MBP. D2R and PKCα expression did not vary among groups. The alteration of the renal dopamine system produced by ovariectomy could account for the defective NKA phosphorylation, the inefficient excretion of sodium load and the development of salt sensitive hypertension. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00450.2014
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    ABSTRACT: Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10 day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia generating enzymes, phosphate-dependent glutaminase (PDG) and phosphoenolpyruvate-carboxykinase (PEPCK), and the ammonia metabolizing enzyme, glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate: 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and, 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00077.2015
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    ABSTRACT: Ischemia-reperfusion injury (IRI) due to hypotension is a common cause of human acute kidney injury (AKI). The hypoxia-inducible transcription factors (HIFs) orchestrate a protective response in renal endothelial and epithelial cells in AKI models. As human MUC1 is induced by hypoxia and enhances HIF-1 activity in cultured epithelial cells, we asked whether Muc1 regulates HIF-1 activity in kidney tissue during IRI. While Muc1 was localized on the apical surface of the thick ascending limb, distal convoluted tubule and collecting duct in the kidneys of sham treated mice, Muc1 appeared in the cytoplasm and nucleus of all tubular epithelia during IRI. Muc1 was induced during IRI, and Muc1 transcripts and protein were also present in recovering proximal tubule cells. Kidney damage was worse and recovery was blocked during IRI in Muc1 KO mice when compared to congenic controls. Muc1 KO mice had reduced levels of HIF-1α, reduced or aberrant induction of HIF-1 target genes involved in the shift of glucose metabolism to glycolysis, and prolonged activation of AMP-activated kinase (AMPK), indicating metabolic stress. Muc1 clearly plays a significant role in enhancing the HIF protective pathway during ischemic insult and recovery in kidney epithelia, providing a new target for developing therapies to treat AKI. Moreover, our data support a role specifically for HIF-1 in epithelial protection of the kidney during IRI as Muc1 is present only in tubule epithelial cells. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00066.2015
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    ABSTRACT: Caffeine is one of the most widely consumed behavioral substances. We have previously shown that caffeine- and theophylline-induced inhibition of renal reabsorption causes diuresis and natriuresis; an effect that requires functional adenosine A1 receptors. In this study, we tested the hypothesis that blocking the Gi protein coupled adenosine A1 receptor via the non-selective adenosine receptor antagonist caffeine changes Na+/H+ exchanger isoform 3 (NHE3) localization and phosphorylation resulting in diuresis and natriuresis. We generated tubulus-specific NHE3 knockout mice (Pax8-Cre), where NHE3 abundance in the S1, S2 and S3 segments of the proximal tubule was completely absent or severely reduced (>85%) in the thick ascending limb. Consumption of fluid and food, as well as glomerular filtration rate, were comparable in control or tubulus-specific NHE3 knockout mice under basal conditions, while urinary pH was significantly more alkaline without evidence for metabolic acidosis. Caffeine self-administration increased total fluid and food intake comparably between genotypes, without significant differences in consumption of caffeinated solution. Acute caffeine application via oral gavage elicited a diuresis and natriuresis that was comparable between control and tubulus-specific NHE3 knockout mice. The diuretic and natriuretic response was independent of changes in total NHE3 expression, phosphorylation of serine-552 and serine-605 or apical plasma membrane NHE3 localization. Although caffeine had no clear effect on localization of the basolateral Na+/bicarbonate cotransporter NBCe1, pretreatment with 4,4'-Diisothiocyanato-2,2'-stilbenedisulfonic acid (DIDS) inhibited caffeine-induced diuresis and natriuresis. In summary, NHE3 is not required for caffeine-induced diuresis and natriuresis. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00129.2015
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    ABSTRACT: The American Journal of Physiology-Renal Physiology is pleased to announce a new series of articles named Mini-Review: Emerging Concepts. The goal of this series of articles is to focus on current topics and emerging areas of research that trainees in renal physiology are addressing. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00179.2015
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    ABSTRACT: A single protein-rich meal (or an infusion of amino acids) is known to increase glomerular filtration rate (GFR) for a few hours, a phenomenon known as "hyperfiltration". This upregulation becomes maladaptive in the long term. Several mediators and paracrine factors have been shown to participate in this upregulation, but they are not directly triggered by protein intake. Here, we explain how a rise in glucagon and vasopressin secretion, directly induced by protein ingestion, might be the initial factors triggering the hepatic and renal events leading to hyperfiltration. Their effects include metabolic actions in the liver and stimulation of sodium chloride reabsorption in the thick ascending limb. Glucagon is not only a glucoregulatory hormone. It is also important for the excretion of nitrogen endproducts by stimulating both urea synthesis in the liver (along with gluconeogenesis from amino acids) and urea excretion by the kidney. Vasopressin allows the concentration of nitrogenous endproducts (urea, ammonia, etc...) and other protein-associated wastes in a hyperosmotic urine, thus allowing significant water economy. No hyperfiltration occurs in the absence of one or the other hormone. Experimetal results suggest that the combined actions of these two hormones, along with complex intrarenal handling of urea, lead to alter the composition of the tubular fluid at the macula densa and to reduce the intensity of the signal activating the tubulo-glomerular feedback control of GFR, thus allowing GFR to raise. Altogether, glucagon, vasopressin, and urea contribute to set up the best compromise between efficient urea excretion and water economy. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00614.2014
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    ABSTRACT: Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with non-invasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4 to 11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labelling technique. Renal function was assessed by eGFR, and renal biopsies were performed when indicated within 5 days of MRI. 26/46 patients had DGF. Of these, 9 patients had acute rejection (including borderline), and 8 had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF-group compared to the group with good allograft function (231±15 vs. 331±15 ml/(min*100g), p<0.001). Living donor allografts exhibited significantly higher perfusion values compared to deceased donor allografts (p<0.001). Renal perfusion significantly correlated with eGFR (r=0.64, p<0.001), resistance index (r=-0.57 p<0.001), and cold ischemia time (r=-0.48, p<0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, non-invasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00064.2015
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    ABSTRACT: Introduction of a new article type for AJP-Renal Phsysiology. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00180.2015
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    ABSTRACT: Inhibiting the epithelial Na(+) channel (ENaC) reduces Cl(-) absorption in cortical collecting ducts (CCD) from aldosterone-treated rats and mice. Since ENaC does not transport Cl(-), the purpose of this study was to explore how ENaC modulates Cl(-) absorption in mouse CCDs perfused in vitro. Therefore, we measured transepithelial Cl(-) flux, JCl, and transepithelial voltage, VT, in CCDs perfused in vitro that were taken from mice consuming a NaCl-replete diet alone or the diet with aldosterone administered by minipump. We observed that application of an ENaC inhibitor (benzamil, 3 μM) to the luminal fluid unmasks conductive Cl(-) secretion. During ENaC blockade, this Cl(-) secretion fell with the application of a non-selective Cl(-) channel blocker (DIDS, 100 μM) to the perfusate. While single channel recordings of intercalated cell apical membrane in split open CCDs demonstrated a Cl(-) channel with properties that resemble the ClC family of Cl(-) channels, ClC-5 is not the primary pathway for benzamil-sensitive Cl(-) flux. 1) in CCDs from aldosterone-treated mice, most Cl(-) absorption is benzamil-sensitive, and 2) Benzamil application stimulates stilbene-sensitive conductive Cl(-) secretion that occurs through a ClC-5-independent pathway. Copyright © 2013, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00471.2013
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    ABSTRACT: Prostatic inflammation is a nearly ubiquitous pathological feature observed in specimens from benign prostate hyperplasia and prostate cancer patients. The microenvironment of the inflamed prostate is highly reactive, and epithelial hyperplasia is a hallmark feature of inflamed prostates. How inflammation orchestrates epithelial proliferation as part of its repair and recovery action is not well understood. Here, we report that a novel epithelial progenitor cell population is induced to expand during inflammation. We used sphere culture assays, immunofluorescence, and flow cytometry to show that this population is increased in bacterially-induced inflamed mouse prostates relative to naïve control prostates. We confirmed from previous reports that this population exclusively possesses the ability to regrow entire prostatic structures from single cell culture using renal grafts. In addition, putative progenitor cells that are harvested from inflamed animals have greater aggregation capacity than those isolated from naïve control prostates. Expansion of this critical cell population requires interleukin 1 signaling, as IL-1R1 null mice exhibit inflammation similar to wild-type inflamed animals, but exhibit significantly reduced progenitor cell proliferation and hyperplasia. These data demonstrate that inflammation promotes hyperplasia in the mouse prostatic epithelium by inducing the expansion of a selected epithelial progenitor cell population in an IL-1R-dependent manner. These findings may have significant impact on our understanding of how inflammation promotes proliferative diseases such as benign prostatic hyperplasia and prostate cancer, both of which depend upon expansion of cells that exhibit a progenitor-like nature. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00488.2014
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    ABSTRACT: In polycystic kidney disease (PKD) the rate of cyst formation and disease progression is highly variable. The lack of predictability in disease progression may be due to additional environmental factors or pathophysiological processes called "third-hits". Diabetes is a growing epidemic and recent studies suggest that PKD patients may be at an increased risk for this disease. We sought to determine if hyperglycemia enhances the initiation and rate of cystogenesis. Adult ift88 conditional floxed allele mice were administered tamoxifen to induce cilia loss in the presence of cre. Subsequent administration of streptozotocin resulted in equivalent hyperglycemia in both cilia (+) and cilia (-) mice. Hyperglycemia with loss of cilia increased the rate of cyst formation and cell proliferation. There were also structural and functional alterations in the kidney, including focal glomerular foot process effacement, interstitial inflammation, formation of primitive renal tubules, polyuria and increased proteinuria in cilia (-) hyperglycemic mice. Gene array analysis indicated enhanced Wnt and epithelial to mesenchymal transition signaling in the kidney of hyperglycemic cilia (-) mice. These data show that hyperglycemia, in the absence of cilia, results in renal structural and functional damage and accelerates cystogenesis, suggesting that diabetes is a risk factor in the progression of PKD. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00652.2014
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    ABSTRACT: Renal fibrosis is a histological outcome of chronic kidney disease (CKD) progression. However, the non-invasive detection of renal fibrosis remains a challenge. Here we constructed a renal fibrosis target mRNA array and used it to detect urinary mRNAs of CKD patients for investigating potential non-invasive biomarkers of renal fibrosis. We collected urine samples from 39 biopsy-proven CKD patients and 11 healthy controls in the training set. Urinary mRNA profiles of 86 genes showed a total of 22 mRNAs that were differentially expressed between CKD patients and controls (P<0.05), and vimentin (VIM) mRNA demonstrated the highest change-fold of 9.99 in CKD versus controls with robust correlations with decline of renal function and severity of tubulointerstitial fibrosis (TIF). Additionally, VIM mRNA further differentiated patients with moderate-to-severe fibrosis from none-to-mild fibrosis group with an AUC of 0.796 (P=0.008). A verification of VIM mRNA in the urine of an additional 96 patients and 20 controls showed that VIM is not only well correlated with renal function parameters, but also correlated with proteinuria, and renal fibrosis scores. Multiple logistic regression and ROC analysis further showed that urine VIM mRNA is the best predictive parameter of renal fibrosis compared to eGFR, Scr and BUN. And there is no improved predictive performance for the composite biomarkers to predict renal fibrosis severity compared to a single gene of VIM. Overall, urinary VIM mRNA might serve as a novel independent non-invasive biomarker to monitor the progression of kidney fibrosis. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00449.2014
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    ABSTRACT: Void spot assays (VSA) and cystometry are two of the most common tests performed in mice, to assess lower urinary tract function. Assay protocols and methodology vary greatly among laboratories, and little is known about reproducibility of results generated by different laboratories. We performed VSA in four mouse strains, comparing males with females and comparing results between two independent laboratories. Unique aspects of the current study include direct comparison of results of VSA performed in a similar manner in two locations and comparison of cystometry performed using two different rates of infusion in these two laboratories. Both assays were performed in male and female 129S1/SvImJ, C57BL/6J, NOD/ShiLtJ, and CAST/EiJ mice and cystometry was performed under urethane anesthesia (10/group). Assays were performed and results analyzed as previously described. Results obtained in female mice were compared to previously reported values. Results of lower urinary tract function testing in mice varies in a consistent manner with strain and gender. Variables in husbandry, testing techniques, and analysis of results can significantly affect conclusions, particularly those obtained by cystometry. Although VSA results were remarkably similar between the two laboratories, consistent methods for performing lower urinary tract function testing in mice are required to compare results among studies with confidence. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00072.2015
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    ABSTRACT: Extracellular nucleotides acting through P2 receptors facilitate natriuresis. To define how purinergic mechanisms are involved in sodium homeostasis, we used transgenic mice (TG) globally over-expressing human CD39 (hCD39, NTPDase1), an ectonucleotidase which hydrolyzes extracellular ATP/ADP to AMP, resulting in altered extracellular purine profile. On a high-sodium diet (HSD, 3.5% Na(+)), urine volume and serum sodium were elevated in TG mice without altering sodium excretion; however, there was significant impairment in HSD-induced decrease in urinary aldosterone in TG mice. Western analysis revealed significantly lower densities ((~)40%) for the β-subunit of the epithelial sodium channel (ENaC) in medulla, and the major band (85-kDa) of γ-ENaC in TG mice cortex. To evaluate aldosterone-independent differences, in a second experiment, aldosterone was clamped by osmotic minipump @ 20 µg/day and mice were fed HSD or a low-sodium diet (LSD, 0.03% Na(+)). Here, no differences in urine volume or osmolality, or serum aldosterone were found, but TG mice showed a modest, yet significant impairment in late natriuresis (days 3 and 4). Several major sodium transporters or channel subunits were differentially expressed between the genotypes. HSD caused down-regulation of Na-Cl cotransporter (NCC) in both genotypes; and had higher cortical levels of NCC, Na-K-ATPase (α-1 subunit), as well as α- and γ-ENaC. The Na-K-2Cl cotransporter (NKCC2) was down-regulated by HSD in WT, but increased in TG mice. In summary, our data support that extracellular nucleotides facilitate natriuresis by countering aldosterone effects, and also reveal aldosterone-independent down-regulation of major renal sodium transporters and channel subunits by purinergic signaling. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00125.2014
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    ABSTRACT: Human genetic linkage and association studies have nominated many genes as possible contributors to disease. Mutating or deleting these genes in a relevant disease model can validate their association with disease and potentially uncover novel mechanisms of pathogenesis. Targeted genetic mutagenesis has only recently been developed in the rat, and this technique has been applied in the Dahl salt-sensitive (S) rat to investigate human candidate genes associated with hypertension. This mini-review communicates the findings of these studies and displays how targeted genetic mutagenesis may contribute to the discovery of novel therapies for patients. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00092.2015
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    ABSTRACT: The mammalian kidney is an organ composed of numerous functional units or nephrons. Beyond the filtering glomerulus of each nephron, various tubular segments with distinct populations of epithelial cells sequentially span the kidney from cortex to medulla. The highly organized folding of the tubules results in a spatial distribution that allows intimate contact between various tubular sub-segments. This unique arrangement can promote a newly recognized type of horizontal epithelial-to- epithelial cross-talk. In this review, we will discuss the importance of this tubular cross-talk in shaping the response of the kidney to acute injury in a sense and sensibility model. We propose that injury-resistant tubules such as S1 proximal segments and thick ascending limbs (TAL) can act as "sensors", and thus modulate the responsiveness or "sensibility" of the S2-S3 proximal segments to injury. We also discuss new findings that highlight the importance of tubular cross-talk in regulating homeostasis and inflammation not only in the kidney, but also systemically. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00030.2015
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    ABSTRACT: Aging men are susceptible to developing lower urinary tract symptoms, but the underlying etiology is unknown and the influence of dietary and environmental factors on them is unclear. We tested whether a folic acid enriched diet changed urinary tract physiology and biology in control male mice and male mice with urinary dysfunction induced by exogenous testosterone and estradiol (T+E2), which mimics changing hormone levels in aging humans. T+E2 treatment increased mouse urine output, time between voiding events, bladder capacity and compliance. Consumption of a folic acid enriched diet moderated these changes without decreasing prostate wet weight or threshold voiding pressure. One potential mechanism for these changes involves water balance. T+E2 treatment increases plasma concentrations of anti-diuretic hormone, which is offset at least in part by a folic acid enriched diet. Another potential mechanism involves neural control of micturition. The folic acid enriched diet, fed to T+E2 treated mice, increased voiding frequency in response to intravesicular capsaicin infusion and increased mRNA abundance of capsaicin-sensitive cation channel, transient receptor potential vanilloid subfamily member 1 (Trpv1), in L6 and S1 dorsal root ganglia (DRG) neurons. T+E2 treatment and a folic acid enriched diet also modified DNA methylation, which is capable of altering gene expression. We found the enriched diet increased global DNA methylation in dorsal and ventral prostate and L6 and S1 DRG. Our results are consistent with folic acid acting to slow or reverse T+E2-mediated alteration in urinary function in part by normalizing water balance and enhancing or preserving afferent neuronal function. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00674.2014
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    ABSTRACT: The objective of this study was to investigate how physiological, pharmacological, and pathological conditions that alter sodium reabsorption (TNa) in the proximal tubule affect oxygen consumption (QO2) and Na(+) transport efficiency (TNa/QO2). To do so, we expanded a mathematical model of solute transport in the proximal tubule of the rat kidney. The model represents compliant S1, S2 and S3 segments, and accounts for their specific apical and basolateral transporters. Sodium is reabsorbed transcellularly, via apical Na(+)/H(+) exchangers (NHE) and Na(+)-glucose (SGLT) cotransporters, and paracellularly. Our results suggest that TNa/QO2 is 80 % higher in S3 than in S1-S2 segments, due to the greater contribution of the passive paracellular pathway to TNa in the former segment. Whereas inhibition of NHE or Na,K-ATPase reduced TNa and QO2, as well as Na(+) transport efficiency. SGLT2 inhibition also reduced proximal tubular TNa but increased QO2; these effects were relatively more pronounced in the S3 versus the S1-S2 segments and in diabetic vs non-diabetic conditions. Diabetes increased TNa and QO2 and reduced TNa/QO2, owing mostly to hyperfiltration. Since SGLT2 inhibition lowers diabetic hyperfiltration, the net effect on TNa, QO2 and Na(+) transport efficiency in the proximal tubule will largely depend on the individual extent to which glomerular filtration rate is lowered. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 04/2015; DOI:10.1152/ajprenal.00007.2015