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: 3.25

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.248

Additional details

5-year impact 3.52
Cited half-life 7.90
Immediacy index 0.78
Eigenfactor 0.03
Article influence 1.05
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 can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Conditions
    • Author's Pre-print on pre-print servers
    • 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
    • May link to publisher version with DOI
    • Publisher last reviewed on 03/06/2015
  • Classification

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The apical Na-K-2Cl co-transporter NKCC2 mediates NaCl reabsorption by the thick ascending limb (TAL). The amount of NKCC2 at the apical membrane of TAL cells is determined by exocytic delivery, recycling, and endocytosis. Surface biotinylation allows measurement of NKCC2 endocytosis but it has low time resolution and does not allow imaging of the dynamic process of endocytosis. We hypothesized that total internal reflection fluorescence (TIRF) microscopy imaging of labeled NKCC2 would allow monitoring of NKCC2 endocytosis in polarized MDCK and TAL cells. Thus we generated an NKCC2 construct containing a biotin acceptor domain (BAD) sequence between the 5th and 6th trans-membrane domains. Once expressed in polarized MDCK or TAL cells, surface NKCC2 was specifically biotinylated by exogenous biotin ligase (BirA). We also demonstrate that expression of a secretory form of BirA in TAL cells induces metabolic biotinylation of NKCC2. Labeling biotinylated surface NKCC2 with fluorescent streptavidin showed that most apical NKCC2 was located within small discrete domains or clusters referred to as 'puncta' on the TIRF field. NKCC2 puncta were observed to disappear from the TIRF field indicating an endocytic event which led to decrease in the number of surface puncta at a rate of 1.18 ± 0.16 % per minute in MDCK cells, and a rate 1.09±0.08 % per minute in TAL cells (n=5). Treating cells with a cholesterol chelating agent (MβCD) completely blocked NKCC2 endocytosis. We conclude that TIRF microscopy of labeled NKCC2 allows the dynamic imaging of individual endocytic events at the apical membrane of TAL cells.
    AJP Renal Physiology 11/2015; DOI:10.1152/ajprenal.00104.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nephrolithiasis is one of the most common urinary tract disorders with the majority of kidney stones composed of calcium oxalate (CaOx). Given its prevalence (US occurrence 10%), it is still poorly understood, lacking progress in identifying new therapies because of its complex etiology. Drosophila melanogaster (fruitfly) is a recently developed model of CaOx nephrolithiasis. Effects of sulfate and thiosulfate on crystal formation were investigated using the Drosophila model, as well as electrophysiological effects on both Drosophila (Slc26a5/6; dprestin) and mouse (mSlc26a6) oxalate transporters utilizing the Xenopus oocyte heterologous expression system. Results indicate that both transport thiosulfate with a much higher affinity than sulfate Additionally, both compounds were effective at decreasing CaOx crystallization when added to the diet. However, these results were not observed when compounds were applied to MTs ex vivo. Neither compound affected CaOx crystallization in dPrestin knock down animals indicating a role for principal cell-specific dPrestin in luminal oxalate transport. Furthermore,thiosulfate has a higher affinity for dPrestin and mSlc26a6 compared to oxalate These data indicate that thiosulfate's ability to act as a competitive inhibitor of oxalate via dPrestin, can explain the decrease in CaOx crystallization seen in the presence of thiosulfate, but not sulfate. Overall, our findings predict that thiosulfate or oxalate-mimics may be effective as therapeutic competitive inhibitors of CaOx crystallization.
    AJP Renal Physiology 11/2015; DOI:10.1152/ajprenal.00406.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Renal artery stenosis is the main cause of renovascular hypertension and results in ischemic nephropathy characterized by inflammation, oxidative stress, microvascular loss and fibrosis with consequent functional failure. Considering the limited number of strategies that effectively control renovascular hypertension and restore renal function, we propose that cell therapy may be a promising option based on the regenerative and immunosuppressive properties of stem cells.. This review addresses the effects of mesenchymal stem cells (MSC) in an experimental animal model of renovascular hypertension known as 2 kidney-1 clip (2K-1C). Significant benefits of MSC treatment have been observed on blood pressure and renal structure of the stenotic kidney. The mechanisms involved are discussed.
    AJP Renal Physiology 11/2015; DOI:10.1152/ajprenal.00341.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Secretion of organic cations (OCs) across renal proximal tubules (RPTs) involves basolateral OCT2-mediated uptake from the blood, followed by apical MATE1/2-mediated efflux into the tubule filtrate. Whereas OCT2 supports electrogenic OC uniport, MATE is an OC/H+ exchanger. As assessed by epifluorescence microscopy, cultured CHO cells that stably express hMATE1 accumulated the fluorescent OC, N,N,N-trimethyl-2-[methyl(7-nitrobenzo[c][l,2,5]oxadiazol-4-yl)amino]ethanaminium (NBD-MTMA) in the cytoplasm and in a smaller, punctate compartment; accumulation in hOCT2 expressing cells was largely restricted to the cytoplasm. A second intracellular compartment was also evident in the multicompartmental kinetics of efflux of the prototypic OC, [3H]MPP, from MATE1-expressing CHO cells. Punctate accumulation of NBD-MTMA was markedly reduced by coexposure of MATE1-expressing cells with 5 μM bafilomycin (BAF), an inhibitor of the V-Type H-ATPase, and accumulation of [3H]MPP and [3H]NBD-MTMA was reduced by >30% by coexposure with 5 μM BAF. BAF had no effect on the initial rate of MATE1-mediated uptake of NBD-MTMA suggesting that the influence of BAF was a secondary effect involving inhibition of the V-type H-ATPase. The accumulation of [3H]MPP by isolated single non-perfused rabbit RPTs was also reduced >30% by coexposure to 5 μM BAF, suggesting that the native expression in RPTs of MATE protein within endosomes can increase steady-state OC accumulation. However, the rate of [3H]MPP secretion by isolated single perfused rabbit RPTs was not affected by 5µM BAF, suggesting that vesicles loaded with OCs+ are not likely to recycle into the apical plasma membrane at a rate sufficient to provide a parallel pathway for OC secretion.
    AJP Renal Physiology 11/2015; DOI:10.1152/ajprenal.00318.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: This work provides an overview of Xie et al. in the context of modern renal physiology and medical imaging. Editorial Focus for F-351-2015.
    AJP Renal Physiology 11/2015; DOI:10.1152/ajprenal.00462.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: MicroRNAs (miRNA) are endogenously produced short non-coding regulatory RNAs that can repress gene expression by posttranscriptional mechanisms. They can therefore influence both normal and pathological conditions in diverse biological systems. Several miRNAs have been detected in kidneys where they have been found to be crucial for renal development and normal physiological functions as well as significant contributors to the pathogenesis of renal disorders such as diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and others due to their effects on key genes involved in these disease processes. miRNAs have also emerged as novel biomarkers in these renal disorders. Due to increasing evidence of their actions in various kidney segments, in this mini-review, we discuss the functional significance of altered miRNA expression during the development of renal pathologies and highlight emerging miRNA-based therapeutics and diagnostic strategies for early detection and treatment of kidney diseases.
    AJP Renal Physiology 11/2015; DOI:10.1152/ajprenal.00387.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: We showed previously that an association of losartan and hydrochlorothiazide, initiated one month after 5/6 nephrectomy (Nx), reversed hypertension and albuminuria and promoted lasting renoprotection. In this new study, we investigated whether equal or even better protection can be obtained by combining losartan and furosemide. Nx was performed in 58 Munich-Wistar rats. One month later, tail-cuff pressure and albuminuria were markedly elevated. At this time, Nx rats were distributed among four groups: Nx (untreated); NxL, receiving losartan; NxLH, receiving losartan and hydrochlorothiazide; and NxLF, given losartan and furosemide. Seven months later, Nx rats exhibited high mortality, severe hypertension, albuminuria, glomerulosclerosis and interstitial fibrosis. Losartan treatment limited mortality and attenuated the renal and hemodynamic abnormalities associated with Nx. As shown previously, the LH association normalized TCP and ALB, prevented renal injury, and reduced mortality to zero. The LF treatment failed to reduce TCP or ALB to normal, and prevented renal injury less efficiently than the LH regimen. The reasons for the differing efficacies of the LF and LH schemes are unclear, and may include beneficial nondiuretic actions of thiazides, such as vasorelaxation and antiproliferative activity. These results refute the established concept that thiazides and thiazide-like diuretics are ineffective at advanced CKD stages. Rather, they suggest that, in view of their renoprotective action, these compounds may even be preferable to loop diuretics in the management of hypertension in advanced CKD.
    AJP Renal Physiology 11/2015; DOI:10.1152/ajprenal.00388.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25(OH)2D3 formation and regulator of mineral metabolism. In klotho-hypomorphic mice (kl/kl) excessive 1,25(OH)2D3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficit, accelerated aging and early death. The kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to stimulation of ADH and aldosterone release. Vitamin-D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone and dietary NaCl all extend the life span of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects growth, tissue calcification and life span of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average life span from 78 days to 127 days. NaHCO3 did not significantly affect plasma concentrations of 1,25(OH)2D3 and Ca2+, but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e. a favorable influence on vascular calcification and early death of klotho-deficient mice.
    AJP Renal Physiology 11/2015; DOI:10.1152/ajprenal.00037.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic kidney disease is associated with vasculitis and is also an independent risk factor for peripheral vascular and coronary artery disease in Diabetic patients. Despite optimal management, a significant number of patients progress towards end-stage renal disease (ESRD), a suggestion that the disease mechanism is far from clear. A reduction in hydrogen sulfide (H2S) has been suggested to play a vital role in diabetic vascular complications including diabetic nephropathy (DN). This mini review highlights the recent findings on the role of hydrogen sulfide (H2S) in mitigating abnormal extracellular matrix metabolism in DN. A discussion on the development of the newer slow releasing H2S compounds and its therapeutic potential is also included.
    AJP Renal Physiology 11/2015; DOI:10.1152/ajprenal.00299.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pendrin is a Na(+)-independent Cl(-)/HCO3 (-) exchanger found in the apical regions of type B and non-A, non-B intercalated cells within the aldosterone-sensitive region of the nephron, i.e. the distal convoluted tubule (DCT), the connecting tubule (CNT) and the cortical collecting duct (CCD). Type B intercalated cells mediate Cl(-) absorption and HCO3 (-) secretion primarily through pendrin-mediated Cl(-)/HCO3 (-) exchange. This exchanger is upregulated with angiotensin II administration and in models of metabolic alkalosis, such as following administration of aldosterone or NaHCO3. In the absence of pendrin-mediated HCO3 (-) secretion, an enhanced alkalosis is observed following aldosterone or NaHCO3 administration. However, probably of more significance is the role of pendrin in the pressor response to aldosterone. Pendrin mediates Cl(-) absorption and modulates aldosterone-induced Na(+) absorption mediated by ENaC. Pendrin changes ENaC channel activity by changing both channel open probability (Po) and surface density (N), at least partly by altering luminal HCO3 (-) and ATP concentration. Thus, aldosterone and angiotensin II stimulate pendrin expression and function, which stimulates ENaC activity, thereby contributing to the pressor response of these hormones. However, pendrin may modulate blood pressure partly through its extra-renal effects. For example, pendrin is expressed in the adrenal medulla, where it modulates catecholamine release. The increase in catecholamine release observed with pendrin gene ablation, likely contributes to the increment in vascular contractile force observed in the pendrin null mouse. This review summarizes the signaling mechanisms that regulate pendrin abundance and function as well as the contribution of pendrin to distal nephron function.
    AJP Renal Physiology 11/2015; DOI:10.1152/ajprenal.00400.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: The renal thiazide-sensitive NaCl cotransporter, NCC, is the major pathway for salt reabsorption in the distal convoluted tubule. The activity of this cotransporter is critical for regulation of several physiological variables such as blood pressure, serum potassium, acid base metabolism, and urinary calcium excretion. Therefore, it is not surprising that numerous hormone signaling pathways regulate NCC activity to maintain homeostasis. In this review we will provide an overview of the most recent evidence on NCC modulation by aldosterone, angiotensin II, vasopressin, glucocorticoids, insulin, norepinephrine, estradiol, progesterone, prolactin and parathyroid hormone.
    AJP Renal Physiology 10/2015; DOI:10.1152/ajprenal.00354.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Renal fibrosis is an inevitable outcome of chronic kidney disease (CKD). Erythropoietin (EPO) has been recently reported to be able to mitigate renal fibrosis. The mechanism underlying the protective effect of EPO, however, remains elusive. In the present study, employing mouse model of renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO), we demonstrated that EPO markedly reduced the disruption of tubular basement membrane (TBM) through attenuating the activation of tissue plasminogen activator (tPA) and matrix metalloproteinase 9 (MMP9), the major matrix proteolytic network in obstructed kidney. Instead of acting directly on tPA in kidney, EPO strongly increased the level of circulating miR-144, which was delivered to the injured renal fibroblasts via extracellular vesicles (EVs) to target tPA 3'-UTR and suppressed tPA expression. The protective effect of EPO on mouse TBM was inhibited by miR-144 antagomir. Furthermore, in vitro results confirmed that EPO could stimulate bone marrow-derived Sca-1+CD44+CD11b-CD19- cells to secret miR-144-containing EVs, which markedly suppressed tPA expression, as well as MMP9 level and activity, in cultured renal fibroblasts. In conclusion, our study provides the first evidence that EPO protects mouse renal TBM through promoting bone marrow cells to generate and secret miR-144, which in turn, is efficiently delivered into the mouse kidney via EVs to inhibit the activation of tPA/MMP9-mediated proteolytic network. This finding thus suggests that EPO, a hormone widely used to treat anemia in chronic kidney disease, is a potential therapeutic strategy for renal fibrosis.
    AJP Renal Physiology 10/2015; DOI:10.1152/ajprenal.00303.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Historically, most FDA approved drugs were the result of "in house" efforts within large pharmaceutical companies. Over the last two decades this paradigm has steadily shifted as the drug industry turned to start ups, small biotechnology companies, and academia for the identification of novel drug target and early drug candidates. This strategic pivot has created new opportunities for groups less traditionally associated with the creation of novel therapeutics, including small academic labs, for engagement in the drug discovery process. A recent example of the successful development of a drug that had its origins in academia is eliglustat tartrate, an oral agent for Gaucher disease type 1.
    AJP Renal Physiology 10/2015; DOI:10.1152/ajprenal.00393.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dynamic contrast-enhanced (DCE) MRI can provide key insight into renal function. DCE MRI is typically achieved through an injection of a gadolinium (Gd)-based contrast agent, which has desirable T1 quenching and tracer kinetics. However, significant T2* blooming effects and signal voids can arise when Gd becomes very concentrated, especially in the renal medulla and pelvis. One MRI sequence designed to alleviate T2* effects is the ultrashort echo time (UTE) sequence. In the present study, we observed T2* blooming in the inner medulla of the mouse kidney, despite using UTE at an echo time of 20 microseconds and a low dose of 0.03 mmol/kg Gd. We applied quantitative susceptibility mapping (QSM) and resolved the signal void into a positive susceptibility signal. The susceptibility values (in ppm) were converted into molar concentrations of Gd using a calibration curve. We determined the concentrating mechanism (referred to as concentrating index) as a ratio of maximum Gd concentration in the inner medulla to the renal artery. The concentrating index was assessed longitudinally over a 17-week course (3, 5, 7, 9, 13, 17 weeks of age). We conclude that the UTE-based DCE method is limited in resolving extreme T2* content caused by the kidney's strong concentrating mechanism. QSM was able to resolve and confirm the source of the blooming effect to be the large positive susceptibility of concentrated Gd. UTE with QSM can complement traditional magnitude UTE and offer a powerful tool to study renal pathophysiology.
    AJP Renal Physiology 10/2015; DOI:10.1152/ajprenal.00351.2015