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

2016 Impact Factor Available summer 2017
2014 / 2015 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: Inflammasomes activate caspase-1 to produce interleukin (IL)-1β. Activation of the NLRP3 inflammasome is involved in various renal pathological conditions. It remains unknown if the NLRP3 inflammasome activation participates in the abnormal renal response to high salt (HS) diet in Dahl salt sensitive (S) rats. In addition, our lab recently showed that transplantation of mesenchymal stem cells (MSCs) attenuated HS-induced inflammation in the renal medulla in Dahl S rat. However, it is unclear if the anti-inflammatory action of MSCs is associated with inhibition of the NLRP3 inflammasome. The present study determined the response of the NLRP3 inflammasome to HS intake and the effect of MSC transplantation on the NLRP3 inflammasome in the renal medulla in Dahl S rats. Immunostaining showed that the inflammasome components NLRP3, ASC and caspase-1 were mainly present in distal tubules and collecting ducts. Interestingly, the renal medullary levels of these inflammasome components were remarkably increased after a HS diet in Dahl S rats, while remaining unchanged in normal rats. This HS-induced activation of the NLRP3 inflammasome was significantly blocked by MSC transplantation into the renal medulla in Dahl S rats. Furthermore, infusion of a caspase-1 inhibitor into the renal medulla significantly attenuated HS-induced hypertension in Dahl S rats. These data suggest that HS-induced activation of the NLRP3 inflammasome may contribute to renal medullary dysfunction in Dahl S rats and that inhibition of inflammasome activation may be one of the mechanisms for the anti-inflammatory and anti-hypertensive effects of stem cells in the renal medulla in Dahl S rats.
    No preview · Article · Jan 2016 · AJP Renal Physiology
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    ABSTRACT: Diabetes increases the reabsorption of Na+ (TNa}) and glucose via the sodium-glucose cotransporter SGLT2 in the early proximal tubule (S1-S2 segments) of the renal cortex. SGLT2 inhibitors enhance glucose excretion and lower hyperglycemia in diabetes. We aimed to investigate how diabetes and SGLT2 inhibition affect TNa and sodium transport-dependent oxygen consumption (Q O2^{active}) along the whole nephron. To do so, we developed a mathematical model of water and solute transport from Bowman space to the papillary tip of a superficial nephron of the rat kidney. Model simulations indicate that in the non-diabetic kidney, acute and chronic SGLT2 inhibition enhances active TNa in all nephron segments, thereby raising QO2^{active} by ~5-12 % in the cortex and medulla. Diabetes increases overall TNa and QO2^{active} by ~50 and 100 %, mainly because it enhances GFR and transport load. In diabetes, acute and chronic SGLT2 inhibition lowers QO2^{active} in the cortex by ~30 %, due to GFR reduction which lowers proximal tubule active TNa, but raises QO2^{active} in the medulla by ~7 %. In the medulla specifically, chronic SGLT2 inhibition is predicted to increase QO2^{active} by 26 % in late proximal tubules (S3 segments), by 2 \% in medullary thick ascending limbs (mTAL), and by 9 and 21 % in outer and inner medullary collecting ducts (OMCD, IMCD), respectively. Additional blockade of SGLT1 in S3 segments enhances glucose excretion, reduces QO2^{active} by 33 % in S3 segments, and raises QO2^{ active} by < 1 % in mTAL, OMCD, and IMCD. In summary, the model predicts that SGLT2 blockade in diabetes lowers cortical QO2^{active} and raises medullary QO2^{active}, particularly in S3 segments.
    No preview · Article · Jan 2016 · AJP Renal Physiology
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    ABSTRACT: It is thought that carbamylated modification plays a crucial role in the development and progression of cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD). However, information on the biological effects of carbamylated high-density lipoprotein (C-HDL) in ESRD is poor. This study investigated the carbamylation level of HDL in ESRD and the effects of C-HDL on endothelial repair properties. HDL was isolated from healthy controls (n = 22) and patients with ESRD (n = 30). The carbamylation level of HDL was detected using enzyme-linked immunosorbent assay (ELISA). Isolated carbamylated HDL for use in tissue culture experiments was carbamylated in vitro to a similar extent to that observed in ESRD. Human arterial endothelial cells (HAECs) were treated with C-HDL or native HDL to assess their migration, proliferation and angiogenesis properties. HDL-associated paraoxonase1 (PON1) activity was also determined by spectrophotometry assay. Compared with healthy controls, the carbamylation level of HDL in ESRD patients was increased and positively correlated with blood urea concentration. In vitro, C-HDL significantly inhibited migration, angiogenesis and proliferation in endothelial cells. Mechanistic studies revealed that HDL-associated PON1 activity was decreased and negatively correlated with carbamylation level of HDL in ESRD patients. In addition, C-HDL suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) and scavenger receptor class B type I (SR-BI) signaling pathways in endothelial cells. In conclusion, this study identified a significantly increased carbamylation level of HDL in ESRD. Furthermore, C-HDL inhibited endothelial cell repair function.
    No preview · Article · Jan 2016 · AJP Renal Physiology
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    ABSTRACT: Evidence has demonstrated that Aldosterone (Aldo) is involved in the development and progression of chronic kidney diseases (CKDs). The purpose of this study was to investigate the role of autophagy in Aldo-induced podocyte damage and the underlying mechanism. Mouse podocytes were treated with Aldo in the presence or absence of 3-methyladenine (3-MA) and NAC. Cell apoptosis was investigated by detecting Annexin V conjugates, apoptotic bodies, caspase-3 activity, and the alteration of podocyte protein nephrin. Autophagy was evaluated by measuring the expressions of LC3, p62, beclin-1 and Atg5. Aldo (10-7 mol/L) induced podocyte apoptosis, autophagy and downregulation of nephrin protein in a time-dependent manner. Aldo-induced apoptosis was further promoted by the inhibition of autophagy via 3-MA and Atg5 siRNA pretreatment. Moreover, Aldo time-dependently increased ROS generation, and H2O2 (10-4 mol/L) application remarkably elevated podocyte autophagy. After treatment with NAC, the autophagy induced by Aldo or H2O2 was markedly attenuated, suggesting a key role of ROS in mediating the autophagy formation in podocytes. Inhibition of ROS also could lessen Aldo-induced podocyte injury. Taken together, our findings suggested that ROS-triggered autophagy played a protective role against Aldo-induced podocyte injury, and targeting autophagy in podocytes may represent a new therapeutic strategy for the treatment of podocytopathy.
    No preview · Article · Jan 2016 · AJP Renal Physiology
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    ABSTRACT: The metabolic status of the kidney is a determinant of injury susceptibility and a measure of progression for many disease processes, however, noninvasive modalities to assess kidney metabolism are lacking. In this study we employed positron emission tomography (PET) and intravital multiphoton microscopy (MPM) to assess cortical and proximal tubule glucose tracer uptake respectively following experimental perturbations of kidney metabolism. Applying dynamic image acquisition PET with 2-18fluoro-2-deoxyglucose (18F-FDG) and tracer kinetic modeling we found that an intracellular compartment in the cortex of the kidney could be distinguished from the blood and urine compartments in animals. Given emerging literature that the tumor suppressor protein p53 is an important regulator of cellular metabolism, we demonstrated that PET imaging was able to discern a three-fold increase in cortical 18F-FDG uptake following the pharmacologic inhibition of p53 in animals. Intravital MPM with the fluorescent glucose analogue 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2-NBDG) provided increased resolution and corroborated these findings at the level of the proximal tubule. Extending our observation of p53 inhibition on proximal tubule glucose tracer uptake, we demonstrated by intravital MPM that pharmacologic inhibition of p53 diminishes mitochondrial potential difference. We provide additional evidence that inhibition of p53 alters key metabolic enzymes regulating glycolysis and increases intermediates of glycolysis. In summary we provide evidence that PET is a valuable tool to examine kidney metabolism in preclinical and clinical studies, intravital MPM is a powerful adjunct to PET in preclinical studies of metabolism, and p53 inhibition alters basal kidney metabolism.
    No preview · Article · Jan 2016 · AJP Renal Physiology
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    ABSTRACT: We used patch-clamp technique to examine whether nitric oxide (NO) decreases NaCl reabsorption by suppressing the basolateral 10-pS Cl- channels in the thick ascending limb (TAL). Both NO synthase substrate L-arginine (L-Arg) and NO donor S-nitroso-N-acetylpenicillamine significantly inhibited the 10-pS Cl- channel activity in the TAL. The inhibitory effect of L-Arg on the Cl- channels was completely abolished in the presence of NO synthase inhibitor or NO scavenger. Moreover, inhibition of soluble guanylyl cyclase abrogated the effect of L-Arg on the Cl- channels, while cGMP analogue 8-BrcGMP mimicked the effect of L-Arg and significantly decreased the 10-pS Cl- channel activity, indicating that NO inhibits the basolateral Cl- channels by increasing cGMP production. Furthermore, treatment of TAL with PKG inhibitor blocked the effect of L-Arg and 8-BrcGMP on the Cl- channels, respectively. In contrast, PDE2 inhibitor had no significant effect on L-Arg or 8-BrcGMP-induced inhibition of the Cl- channels. Therefore, we conclude that NO decreases the basolateral 10-pS Cl- channel activity through cGMP-dependent PKG pathway, which may contribute to the natriuretic and diuretic effects of NO in vivo.
    No preview · Article · Jan 2016 · AJP Renal Physiology
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    ABSTRACT: Autosomal-dominant polycystic kidney disease is a common cause of end-stage renal disease, and no approved treatment is available in the US to slow disease progression. The mTOR signaling pathway is aberrantly activated in renal cysts, and, while mTOR inhibitors are highly effective in rodent models, clinical trials in ADPKD have been disappointing due to dose-limiting extra-renal side effects. Since mTOR is known to be regulated by nutrients and cellular energy status we hypothesized that dietary restriction may affect renal cyst growth. Here we show that reduced food intake (RFI) by 23% profoundly affects polycystic kidneys in an orthologous mouse model of ADPKD with a mosaic conditional knockout of PKD1. This mild level of RFI does not affect normal body weight gain, cause malnutrition or any other apparent side effects. RFI substantially slows disease progression: relative kidney weight increase was 41% vs. 151% in controls, proliferation of cyst-lining cells was 7.7% vs. 15.9% in controls. Mice on RFI diet maintained kidney function and did not progress to end-stage renal disease. The two major branches of mTORC1 signaling, S6 and 4EBP1, are both suppressed in cyst-lining cells by RFI suggesting that this dietary regimen may be more broadly effective than pharmacological mTOR inhibition with rapalogues which primarily affects the S6 branch. These results indicate that polycystic kidneys are exquisitely sensitive to minor reductions in nutrient supply or energy status. This study suggests that a mild decrease in food intake represents a potential therapeutic intervention to slow disease progression in ADPKD patients.
    No preview · Article · Jan 2016 · AJP Renal Physiology
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    ABSTRACT: Glomerular integrity and functions are maintained by growth factor (GF) signaling. Heparan sulfate, the major component of glomerular extracellular matrices modulates GF signaling, but its roles in the glomerular homeostasis are unknown. We investigated the roles of heparan sulfate 6-O-endosulfatases, Sulf1 and Sulf2, in glomerular homeostasis. Both Sulf1 and Sulf2 were expressed in the glomeruli of wild type (WT) mice. Sulf1 and Sulf2 double-knockout (DKO) mice showed glomerular hypercellularity, matrix accumulation, mesangiolysis and glomerular basement membrane irregularity. Platelet-derived growth factor-B (PDGF-B) and PDGF receptor-β were up-regulated in Sulf1 and Sulf2 DKO mice compared with WT mice. Glomeruli from Sulf1 and Sulf2 DKO mice in vitro stimulated either by PDGF-B, vascular endothelial growth factor (VEGF) or transforming growth factor beta (TGF-β) similarly showed reduction of phospho-Akt, phospho-Erk1/2 and phospho-Smad2/3, respectively. Since glomerular lesions in Sulf1 and Sulf2 DKO mice were reminiscent of diabetic nephropathy, we examined the effects of Sulf1 and Sulf2 gene disruption in streptozotocin-induced diabetes. Diabetic WT mice showed up-regulation of glomerular Sulf1 and Sulf2 mRNA by in situ hybridization. Diabetic DKO mice showed significant increases in albuminuria and serum creatinine, and acceleration of glomerular pathology without glomerular hypertrophy, those were associated with reduction of glomerular phospho-Akt. In conclusion, Sulf1 and Sulf2 play indispensable roles to maintain glomerular integrity and protective roles in diabetic nephropathy probably by growth factors modulation.
    No preview · Article · Jan 2016 · AJP Renal Physiology
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    ABSTRACT: A low Na, high K diet (LNaHK) is considered a healthier alternative to the "Western" high Na diet. Because the mechanism for K secretion involves Na reabsorptive exchange for secreted K in the distal nephron, it is not understood how K is eliminated with such low Na intake. Animals on LNaHK produce an alkaline load, high urinary flows, and markedly elevated plasma angiotensin II (ANGII) and aldosterone (aldo) levels in order to maintain K balance. Recent studies have revealed a potential mechanism involving the actions of alkalosis, urinary flow, elevated ANGII, and aldo on two types of potassium channels, ROMK and BK, located in principal and intercalated cells. Here we review these recent advances.
    Preview · Article · Jan 2016 · AJP Renal Physiology
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    ABSTRACT: Development of vascular calcification (VC) in chronic uremia (CU) is a tightly regulated process controlled by factors promoting and inhibiting mineralization. Next generation high-throughput RNA sequencing (RNA-seq) is a powerful and sensitive tool for quantitative gene expression profiling and detection of differentially expressed genes. Here, we for the first time use RNA-seq to examine rat aorta transcriptomes from CU rats compared to controls. Severe VC was induced in CU rats which lead to extensive changes in the transcriptional profile. Among the 10153 genes with an expression level >1 reads/kilobase-transcript/million mapped reads (RPKM), 2665 genes were differentially expressed with 47% up- and 53% downregulated genes in uremic rats. Significantly deregulated genes were enriched for ontologies related to extracellular matrix, response to wounding, organic substance, and ossification. The individually affected genes were of relevance to osteogenic transformation, tissue calcification, and Wnt modulation. Downregulation of the Klotho gene in uremia is believed to be involved in development of VC, but it is debated whether the effect is caused by circulating Klotho only, or if Klotho is produced locally in the vasculature. We found that Klotho was neither expressed in normal nor in calcified aorta by RNA-seq. In conclusion, we demonstrated extensive changes in the transcriptional profile of the uremic, calcified aorta, which were consistent with a shift in phenotype from vascular tissue toward an osteochondrocytic transcriptome profile. Moreover, neither normal vasculature nor the calcified vasculature in chronic uremia is expressing Klotho.
    Preview · Article · Jan 2016 · AJP Renal Physiology
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    ABSTRACT: Our previous studies suggest a critical role of Reticulon-1A (RTN1A) in mediating endoplasmic reticulum (ER) stress in kidney cells of animal models and human with kidney diseases. A large body of evidence suggests that proteinuria itself can cause tubular cell injury leading to the progression of kidney disease. Here, we determined whether RTN1A mediates proteinuria-induced tubular cell injury through increased ER stress. We found that the incubation of HK2 cells with human serum albumin (HAS) induced the expression of RTN1A and ER stress markers, while knockdown of RTN1A expression attenuated HAS-induced ER stress and tubular cell apoptosis in vitro. In vivo, we found that the tubular cell-specific RTN1 knockdown resulted in significant attenuation of tubular cell ER stress, apoptosis, and renal fibrosis in a model of albumin-overload nephropathy. Based on these findings, we conclude that RTN1A is a key mediator for proteinuria-induced tubular cell toxicity and renal fibrosis.
    Preview · Article · Jan 2016 · AJP Renal Physiology