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
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: The ascending thin limbs (ATLs) and lower descending thin limbs (DTLs) of Henle's loop in the inner medulla of the rat are highly permeable to urea and yet no urea transporters have been identified in these sections. We hypothesized that novel, yet unidentified transporters in these tubule segments could explain the high urea permeability. cDNAs encoding for SGLT1a, NaGLT1, UT-A2c, and UT-A2d were isolated and cloned from the Munich-Wistar rat inner medulla. SGLT1a is a novel amino-terminal truncated variant of the Na(+)-glucose transporter, SGLT1. NaGLT1 is another Na(+)-glucose transporter primarily located in the proximal tubules and not previously described in the thin limbs. UT-A2c and UT-A2d are novel variants of the urea transporter, UT-A2. UT-A2c is truncated at the carboxyl terminus and UT-A2d has one exon skipped. When rats underwent water restriction for 72 h, mRNA levels of SGLT1a increased in the ATLs, NaGLT1 levels increased in both ATLs and DTLs and UT-A2c increased in the ATLs. [(14)C]urea uptake assays performed on Xenopus oocytes heterologously expressing these proteins revealed that despite having structural differences from their full-length versions, SGLT1a, UT-A2c and UT-A2d enhanced urea uptake. NaGLT1 also facilitated urea uptake. Uptakes were Na(+)-independent and inhibitable by phloretin and/or phloridzin. Our data indicate that there are several alternative channels for urea in the rat inner medulla that could potentially contribute to the high urea permeabilities in the thin limb segments.
    AJP Renal Physiology 10/2015; DOI:10.1152/ajprenal.00392.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Enigma Resolved: Phospholipase A2 Receptor-1 is the Cause of "Idiopathic" Membranous Glomerulonephritis.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00264.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Podocytes constitute the outer layer of the glomerular filtration barrier where they form an intricate network of interdigitating foot processes which are connected by slit diaphragms. A hitherto unanswered puzzle concerns the question whether slit diaphragms are established between foot processes of the same podocyte or between foot processes of different podocytes. By employing focused ion beam-scanning electron microscopy (FIB-SEM) we provide unequivocal evidence that slit diaphragms are formed between foot processes of different podocytes. We extended our investigations of the filtration slit by using dual-axis electron tomography of human and mouse podocytes as well as of Drosophila nephrocytes. Using this technique we not only find a single slit diaphragm which spans the filtration slit around the whole periphery of the foot processes but additional punctate filamentous contacts between adjacent foot processes. Future work will be necessary to determine the proteins constituting the two types of cell-cell contacts.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00338.2015
  • AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00418.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aldosterone increases blood pressure (BP) by stimulating sodium (Na) reabsorption within the distal nephron and collecting duct (CD). Aldosterone also stimulates endothelin-1 (ET-1) production that acts within the CD to inhibit Na reabsorption via a negative feedback mechanism. We tested the hypothesis that this renal aldosterone-endothelin feedback system regulates electrolyte balance and BP by comparing the effect of a high-salt (NaCl) diet and mineralocorticoid stimulation in control and CD specific ET-1 knockout mice (CD ET-1 KO). Metabolic balance and radiotelemetric BP were measured before and after treatment with desoxycorticosterone pivalate (DOCP) in mice fed a high-salt diet with saline to drink. CD ET-1 KO mice consumed more high-salt diet and saline and had greater urine output than controls. CD ET-1 KO mice exhibited increased BP and greater fluid retention and body weight (BW) than controls on a high-salt diet. DOCP with high-salt feeding further increased BP in CD ET-1 KO mice and by the end of the study the CD ET-1 KO mice are substantially hypernatremic. Unlike controls, CD ET-1 KO mice failed to respond acutely to or escape from DOCP treatment. We conclude that local ET-1 production in the CD is required for the appropriate renal response to Na loading and lack of local ET-1 results in abnormal fluid and electrolyte handling when challenged with a high-salt diet and with DOCP treatment. Additionally, local ET-1 production is necessary, under these experimental conditions, for renal compensation to, and escape from, the chronic effects of mineralocorticoids.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00220.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular disease including cardiac hypertrophy is common in patients with kidney disease, and can be partially attenuated using blockers of the renin angiotensin system (RAS). It is unknown whether cardiac microRNAs contribute to pathogenesis of cardiac hypertrophy or to the protective effect of RAS blockade in kidney disease. Using subtotal nephrectomy rat model of kidney injury, we investigated changes in cardiac microRNAs that are known to have direct target genes involved in regulation of apoptosis, fibrosis and hypertrophy. The effect of treatment with the angiotensin converting enzyme inhibitor (ACEi), ramipril on cardiac microRNAs was also investigated. Kidney injury led to a significant increase in cardiac microRNA-212 and microRNA-132 expression. Ramipril reduced cardiac hypertrophy, attenuated the increase in microRNA-212 and microRNA-132 and significantly increased microRNA-133 and microRNA-1 expression. There was altered expression of Caspase-9, B-cell lymphoma 2, transforming growth factor-beta, fibronectin 1, collagen 1a1 and forkhead box proteins O3, all known to be involved in the regulation of apoptosis, fibrosis and hypertrophy in cardiac cells, whilst being targets for the above microRNAs. ACEi treatment increased expression of microRNA-133 and microRNA-1. Inhibitory action of ACEi treatment on increased cardiac NOX1 expression after STNx surgery suggest that inhibition of oxidative stress is also one of mechanism of ACEi mediated cardioprotection. These finding suggests the involvement of microRNAs in the cardioprotective action of ACEi in acute renal injury, which is mediated through an inhibitory action on pro-fibrotic and pro-apoptotic target genes, and stimulatory action on anti-hypertrophic and anti-apoptotic target genes.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00183.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Long noncoding RNAs (lncRNAs) are emerging as key species-specific regulators of cellular and disease processes. To identify potential lncRNAs relevant to acute and chronic renal epithelial injury, we performed unbiased whole transcriptome profiling of human proximal tubular epithelial cells (PTECs) in hypoxic and inflammatory conditions. RNA sequencing (RNA-seq) revealed that the protein-coding and noncoding transcriptomic landscape differed between hypoxia-stimulated and cytokine-stimulated human PTECs. Hypoxia- and inflammation-modulated lncRNAs were prioritized for focused follow up according to their degree of induction by these stress stimuli, their expression in human kidney tissue, and whether exposure of human PTECs to plasma of critically ill sepsis patients with acute kidney injury modulated their expression. For three lncRNAs--MIR210HG, linc-ATP13A4-8, and linc-KIAA1737-2--that fulfilled our criteria, we validated their expression patterns, examined their loci for conservation and synteny, and defined their associated epigenetic marks. The lncRNA landscape characterized here provides insight into novel transcriptomic variations in the renal epithelial cell response to hypoxic and inflammatory stress.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00290.2015
  • AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00404.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: In a lentivirus-based gene delivery system, the incorporated gene is continuously expressed for a long time. In this study, we devised a simple way to knock down a specific gene in a kidney cell-specific pattern in adult mice by lentivirus-assisted transfer of shRNA. Kidney collecting duct (CD)-specific aquaporin-3 (AQP3)-knockdown mice was generated by consecutive injection of Hoxb7-Cre-expressing lentivirus (LV-Hoxb7 Cre) and loxP-AQP3 shRNA-expressing lentivirus (LV-loxP shAQP3) in adult C57BL6/J mice. LV-Hoxb7 Cre was designed to express mCherry, while LV-loxP shAQP3 was designed with a floxed EGFP tagged stop sequence, and thus EGFP would be expressed only in the absence of Cre recombination.. In mice treated with LV-Hoxb7 Cre alone, mCherry protein expression, which indicates the presence of Cre recombinase, occurred only in CD cells. However, LV-loxP shAQP3 injection alone resulted in an increase in EGFP expression in all kidney cells, indicating the transcription of the floxed region. When LV-Hoxb7 Cre and LV-loxP shAQP3 were sequentially transduced, EGFP expression was attenuated while mCherry expression was sustained in CD cells demonstrating a CD cell specific recombination of the floxed region. AQP3 expression in mice injected with LV-Hoxb7 Cre or LV-loxP shAQP3 alone did not differ, but consecutive injection of LV-Hoxb7 Cre and LV-loxP shAQP3 significantly reduced AQP3 expression in CD cells. However, the expression levels of AQP3 were not altered in other cell types. Double transduction of Cre- and loxP-based lentivirus can easily generate kidney cell-specific knockdown mice, and this method might be applicable to other species.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00251.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Phylogentically, the organic anion transporters 1 (OAT1) and OAT3 are closely related whereas OAT2 is more distant. Experiments with HEK293 cells stably transfected with human OAT1, OAT2, or OAT3 were performed to compare selected transport properties. Common to OAT1, OAT2, and OAT3 is their ability to transport cGMP. OAT2 interacted with prostaglandins (PGs) and cGMP uptake was inhibited by PGE2 and PGF2α with IC50 values of 40.8 µM and 12.7 µM, respectively. OAT1 (IC50 23.7 µM), OAT2 (IC50 9.5 µM), and OAT3 (IC50 1.6 µM) were potently inhibited by MK571, an established multidrug resistance protein (MRP) inhibitor. OAT2-mediated cGMP uptake was not inhibited by short-chain monocarboxylates and, as opposed to OAT1 and OAT3, not by dicarboxylates. Consequently, OAT2 showed no cGMP-glutarate exchange. OAT1 and OAT3 exhibited a pH and a chloride dependence with higher substrate uptake at acidic pH and lower substrate uptake in the absence of chloride, respectively. Such pH and chloride dependencies were not observed with OAT2. Depolarization of membrane potential by high potassium concentrations in the presence of the potassium ionophore valinomycin left cGMP uptake unaffected. In addition to cGMP, OAT2 transported urate and glutamate, but cGMP-glutamate exchange could not be demonstrated. These experiments suggest that OAT2-mediated cGMP uptake does not occur via exchange with monocarboxylates, dicarboxylates, and hydroxyl ions. The counter anion for electroneutral cGMP uptake remains to be identified.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00140.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Podocytes are highly specialized epithelial cells located at the outer aspects of the glomerular capillary tuft and critical components of the kidney filtration barrier. To maintain their unique features podocytes express a number of proteins that are only sparsely found elsewhere in the body. In this study, we have identified four (Tmem234, Znf185, Lrrc49, and Slfn5) new highly podocyte-enriched proteins. The proteins are strongly expressed by podocytes while other parts of the kidney show only weak or no expression. Tmem234, Slfn5 and Lrrc49 are located to foot processes, whereas Znf185 is found in both foot and major processes. Expressional studies in developing kidneys show that these proteins are first expressed at the capillary stage glomerulus, the same stage when the formation of major and foot processes begins. We identified zebrafish orthologues for Tmem234 and Znf185 genes, and inactivated their expression using morpholino technology. Studies in zebrafish larvae indicate that Tmem234 is essential for the organization and functional integrity of the pronephros filtration barrier as knockdown of Tmem234 expression results in foot process effacement and proteinuria. In summary, we have identified five novel highly podocyte-enriched proteins and show that one of them, Tmem234, is essential for the normal filtration barrier in zebrafish pronephros. Identification of new molecular components of the kidney filtration barrier opens up possibilities to study their role in the glomerulus biology and diseases.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00525.2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have previously demonstrated that the circadian clock protein Per1 coordinately regulates multiple genes involved in sodium reabsorption in renal collecting duct cells. Consistent with these results, Per1 KO mice exhibit dramatically lower blood pressure than WT mice. The proximal tubule is responsible for a majority of sodium reabsorption. Previous work has demonstrated that expression of the sodium hydrogen exchanger NHE3 oscillates with a circadian pattern and SGLT1 has been demonstrated to be a circadian target in the colon, but whether these target genes are regulated by Per1 has not been investigated in the kidney. The goal of this study was to determine if Per1 regulates the expression of NHE3, SGLT1, and SGLT2 in the kidney. Pharmacological blockade of nuclear Per1 entry resulted in decreased mRNA expression of SGLT1 and NHE3, but not SGLT2 in the renal cortex of mice. Per1 siRNA and pharmacological blockade of Per1 nuclear entry in human proximal tubule HK-2 cells yielded the same results. Examination of heterogeneous nuclear RNA (hnRNA) suggested that the effects of Per1 on NHE3 and Sglt1 expression occurred at the level of transcription. Chromatin-immunoprecipitation experiments demonstrated the interaction of Per1 and the circadian protein CLOCK with the promoters of NHE3 and SGLT1. These interactions were reduced by blockade of Per1 nuclear entry. Importantly, both membrane and intracellular protein levels of NHE3 and SGLT1 were decreased following blockade of nuclear Per1 entry. These data demonstrate a role for Per1 in the transcriptional regulation of NHE3 and SGLT1 in the kidney.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00197.2014
  • AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00398.2015
  • AJP Renal Physiology 09/2015; 309(3):F271. DOI:10.1152/ajprenal.00239.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cytomegalovirus (CMV) infection is a frequent complication early post-transplant. This study examines its impact on chronic allograft changes, long-term graft loss and patient survival. We studied 594 patients who had protocol biopsies at 6 weeks, 3 and 6 months post-transplant. Chronic allograft changes were evaluated according to the updated Banff classification (IF/TA (interstitial fibrosis/tubular atrophy), vascular and glomerular lesions). Follow up data was available up to 10 years. CMV infection was diagnosed in 153 of 594 patients (26%) in the first year after transplantation, mostly within the first 3 months. Graft survival was reduced in patients with CMV (p=0.03) as well as the combined allograft/patient survival (p=0.008). Prevalence of IF/TA at 6 weeks after transplantation was already 3-fold higher in patients who experienced CMV infection later-on, compared to patients without CMV (p=0.005). In multivariate analyses CMV viremia or disease were not a significant factor for graft loss or death. In conclusion, patients with CMV infection post-transplant show more chronic allograft changes early-on -even before CMV infection- and development of IF/TA is not more prevalent in patients with CMV. Our data do not support a significant role of CMV in patient and graft outcomes.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00317.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Evidences in rodents suggest that tacrolimus-induced post-transplant hypertension is due to upregulation of the thiazide-sensitive Na+-Cl- cotransporter, NCC. Here we analyzed if a similar mechanism is involve in post-transplant hypertension in humans. From January 2013 to June 2014 all adult kidney transplant recipients receiving a kidney allograft were enrolled into a prospective cohort study. All patients received tacrolimus as part of the immunosuppressive therapy. Six months after surgery we assessed general clinical and laboratory variables, tacrolimus trough blood levels, and ambulatory 24-hour blood pressure monitoring. Urinary exosomes were extracted to perform Western blot analysis using total and phospho-NCC antibodies. A total of 52 patients, including 17 women and 35 men, were followed. At six months after transplantation, of the 35 men, 17 developed hypertension and 18 remained normotensive, while high blood pressure was observed in only 3 out 17 women. The hypertensive patients were significantly older than the normotensive group, however there were no significant differences in body weight, history of acute rejection, renal function, and tacrolimus through levels. In urinary exosomes, hypertensive patients showed higher NCC expression (1.7 ± 0.19) than normotensive (1 ± 0.13) (P=0.0096). Also, NCC phosphorylation levels were significantly higher in the hypertensive patients (1.57 ± 0.16 vs. 1 ± 0.07; P=0.0049). Our data show that there is a positive correlation between NCC expression/phosphorylation in urinary exosomes with the development of hypertension in post-transplant male patients treated with tacrolimus. Our results are consistent with the hypothesis that NCC activation plays a major role in tacrolimus-induced hypertension. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00326.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Rab GTPase-activating protein TBC1D4 (AS160) controls trafficking of the glucose transporter GLUT4 in adipocytes and skeletal muscle cells. TBC1D4 is also highly abundant in the renal distal tubule, although its role in this tubule is so far unknown. In vitro studies suggest that it is involved in the regulation of renal transporters and channels such as ENaC, AQP2 and the Na(+)-K(+)-ATPase. To assess the physiological role of TBC1D4 in the kidney, wild-type (TBC1D4(+/+)) and TBC1D4-deficient (TBC1D4(-/-)) mice were studied. Unexpectedly, neither under standard nor under challenging conditions (low Na(+)/high K(+), water restriction) did TBC1D4-deficient mice show any difference in urinary Na(+) and K(+) excretion, urine osmolarity, plasma ion and aldosterone levels, and blood pressure when compared to TBC1D4(+/+) mice. Also immunoblotting did not reveal any change in the abundance of major renal sodium and water transporting proteins (NKCC2, NCC, ENaC, AQP2, and the Na(+)-K(+)-ATPase). However, the abundance of GLUT4, which co-localizes with TBC1D4 along the distal nephron of TBC1D4(+/+) mice, was lower in whole kidney lysates of TBC1D4(-/-) mice than in TBC1D4(+/+) mice. Likewise, primary thick ascending limb (TAL) cells isolated from TBC1D4(-/-) mice showed an increased basal glucose uptake and an abrogated insulin response when compared to TAL cells from TBC1D4(+/+) mice. Thus, TBC1D4 is dispensable for the regulation of renal Na(+) and water transport, but may play a role for GLUT4-mediated basolateral glucose uptake in distal tubules. The latter may contribute to the known anaerobic glycolytic capacity of distal tubules during renal ischemia. Copyright © 2015, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00139.2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vascular calcification (VC) is a critical complication in patients with chronic kidney disease (CKD). The effects of spironolactone (SPL), a mineralocorticoid receptor (MR) antagonist, on VC have not been fully investigated in CKD. The present in vivo study determined the protective effects of SPL on VC in CKD rats. Rats were divided into a control group and four groups of rats with adenine-induced CKD. Three groups were treated with 0, 50, and 100 mg/kg/day SPL for 8 weeks, and one group was treated with 100 mg/kg/day SPL for the last 2 weeks of the 8-week treatment period. After 8 weeks, CKD rats developed azotemia and hyperphosphatemia, with increases in the expression of serum and glucocorticoid-regulated kinase-1 and sodium-phosphate cotransporter, in inflammation and oxidative stress level, in osteogenic signaling and apoptosis, and in aortic calcification, compared with control rats. SPL dose-dependently decreased these changes in the aortas, concomitant with improvements in renal inflammation, tubulointerstitial nephritis, and kidney function. SPL neither lowered blood pressure level nor induced hyperkalemia. Treatment of CKD rats for the last 2 weeks with 100 mg/kg/day SPL attenuated VC compared with CKD rats with the same degree of kidney function and hyperphosphatemia. In conclusion, SPL dose-dependently inhibits the progression of VC by suppressing MR signaling, local inflammation, osteogenic transition, and apoptosis in the aortas of CKD rats. Copyright © 2014, American Journal of Physiology - Renal Physiology.
    AJP Renal Physiology 09/2015; DOI:10.1152/ajprenal.00669.2014