6,438 results match your criteria American Journal of Physiology - Renal Physiology[Journal]


SEX DIFFERENCES IN ENDOTHELIAL FUNCTION IN CHRONIC KIDNEY DISEASE.

Am J Physiol Renal Physiol 2020 May 18. Epub 2020 May 18.

Division of Nephrology, University of Iowa, United States.

Vascular dysfunction plays an important role in the etiology of chronic kidney disease (CKD), and is associated with cardiovascular diseases (CVD). Sex differences in vascular function are common in clinical and non-clinical populations. However, no data exist in individuals with CKD. Read More

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http://dx.doi.org/10.1152/ajprenal.00156.2020DOI Listing

Monophosphoryl lipid A pretreatment suppresses sepsis- and LPS-induced proinflammatory cytokine production in medullary thick ascending limb.

Am J Physiol Renal Physiol 2020 May 18. Epub 2020 May 18.

University of Texas Medical Branch.

Sepsis is the leading cause of acute kidney injury in critically ill patients. Tumor necrosis factor-α (TNF-α) is implicated in the pathogenesis of septic kidney injury; however, the sites and mechanisms of renal TNF-α production during sepsis remain to be defined. In this study, we show that TNF-α expression is increased in medullary thick ascending limbs (MTAL) of mice with sepsis induced by cecal ligation and puncture. Read More

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http://dx.doi.org/10.1152/ajprenal.00178.2020DOI Listing

Is the kidney a target of SARS-CoV-2?

Am J Physiol Renal Physiol 2020 May 15. Epub 2020 May 15.

UNAM, Instituto de Investigaciones Biomédicas and Instituto Nacional de Ciencias Médicas y Nutrición.

The new disease produced by the Severe Acute Respiratory Syndrome - coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China in December 2019, there is compelling evidence that novel SARS-CoV-2 is a highly transmissible virus, and it is associated to a broad clinical spectrum going from subclinical presentation to severe respiratory distress and multi-organ failure. Like other coronaviruses, SARS-CoV-2 recognizes the human Angiotensin Converting Enzyme 2 (hACE2) as a cellular receptor that allows it to infect different host cells, and likely disrupts the renin-angiotensin-aldosterone system (RAAS) homeostasis. Read More

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http://dx.doi.org/10.1152/ajprenal.00160.2020DOI Listing

Tensin2 is important for podocyte-glomerular basement membrane interaction and integrity of glomerular filtration barrier.

Am J Physiol Renal Physiol 2020 May 11. Epub 2020 May 11.

Department of Human Sciences, Osaka International University, Japan.

Tensin2 (Tns2), an integrin-linked protein, is enriched in podocytes within the glomerulus. Previous studies revealed that Tns2-deficient mice exhibited defects of the glomerular basement membrane (GBM) soon after birth in a strain-dependent manner. However, the mechanisms for the onset of defects caused by Tns2 deficiency remain unidentified. Read More

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http://dx.doi.org/10.1152/ajprenal.00055.2020DOI Listing

Inhibition of interleukin-6 on matrix protein production by glomerular mesangial cells and its pathway involved.

Am J Physiol Renal Physiol 2020 May 11. Epub 2020 May 11.

University of North Texas Health Science Center.

Activation of immunologic pathways and disturbances of the extracellular matrix (ECM) dynamics are important contributors to the pathogenesis of chronic kidney diseases. Glomerular mesangial cells (MCs) are critical for homeostasis of glomerular ECM dynamics. Interleukin-6 (IL6) can act as a pro/anti- inflammatory agent relative to cell types and conditions. Read More

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http://dx.doi.org/10.1152/ajprenal.00043.2020DOI Listing

CBX7 suppression prevents kidney against ischemia and reperfusion injury induced endoplasmic reticulum stress through Nrf-2/HO-1 pathway.

Am J Physiol Renal Physiol 2020 May 11. Epub 2020 May 11.

Department of Urology, Renmin Hospital of Wuhan University, China.

Renal ischemia/reperfusion injury (I/R) usually occurs in renal transplantation and partial nephrectomy, which could lead to acute kidney injury. However, the effective treatment for renal I/R still remains limited. In the present study, we investigated whether inhibition of CBX7 could attenuate renal I/R injury in vivo and in vitro, as well as the potential mechanisms. Read More

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http://dx.doi.org/10.1152/ajprenal.00088.2020DOI Listing

Depletion of macrophages slows the early progression of renal injury in obese Dahl salt-sensitive leptin receptor mutant rats.

Am J Physiol Renal Physiol 2020 May 11. Epub 2020 May 11.

Pharmacology and Toxicology, University of Mississippi Medical Center, United States.

Recently, we reported that obese Dahl salt-sensitive leptin receptor mutant (SSmutant) rats display progressive renal injury. The current study demonstrated that the early development of renal injury in the SSmutant strain is associated with an increase in the renal infiltration of macrophages compared to lean SS rats. We also examined whether depletion of macrophages with clodronate would reduce the early progression of renal injury in the SSmutant strain. Read More

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http://dx.doi.org/10.1152/ajprenal.00100.2020DOI Listing

Developmental loss, but not pharmacological suppression, of renal carbonic anhydrase 2 results in pyelonephritis susceptibility.

Am J Physiol Renal Physiol 2020 Jun 11;318(6):F1441-F1453. Epub 2020 May 11.

Division of Pediatric Nephrology, Department of Pediatrics, Indiana University, Indianapolis, Indiana.

Carbonic anhydrase II knockout () mice have depleted numbers of renal intercalated cells, which are increasingly recognized to be innate immune effectors. We compared pyelonephritis susceptibility following reciprocal renal transplantations between and wild-type mice. We examined the effect of pharmacological CA suppression using acetazolamide in an experimental murine model of urinary tract infection. Read More

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http://dx.doi.org/10.1152/ajprenal.00583.2019DOI Listing

GLP-1-induced renal vasodilation in rodents depends exclusively on the known GLP-1 receptor and is lost in prehypertensive rats.

Am J Physiol Renal Physiol 2020 Jun 11;318(6):F1409-F1417. Epub 2020 May 11.

Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate postprandial insulin release. However, GLP-1 also exerts extrapancreatic effects, including renal effects. Some of these renal effects are attenuated in hypertensive rats, where renal expression of GLP-1 receptors is reduced. Read More

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http://dx.doi.org/10.1152/ajprenal.00579.2019DOI Listing

Dietary fructose enhances angiotensin II-stimulated Na transport via activation of PKCα in renal proximal tubules.

Am J Physiol Renal Physiol 2020 May 11. Epub 2020 May 11.

Physiology and Biophysics, Case Western Reserve University, United States.

Angiotensin II (Ang II) stimulates proximal nephron transport via activation of classical protein kinase C (PKC) isoforms. Acute fructose treatment stimulates PKC and dietary fructose enhances Ang II's ability to stimulate Na transport, but the mechanisms are unclear. We hypothesized that dietary fructose enhances Ang II's ability to stimulate renal proximal tubule Na reabsorption by augmenting PKCα activation and increases in intracellular calcium (Ca). Read More

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http://dx.doi.org/10.1152/ajprenal.00543.2019DOI Listing

Open microfluidic coculture reveals paracrine signaling from human kidney epithelial cells promotes kidney specificity of endothelial cells.

Am J Physiol Renal Physiol 2020 May 11. Epub 2020 May 11.

Chemistry, University of Washington, United States.

Endothelial cells (ECs) from different human organs possess organ-specific characteristics that support specific tissue regeneration and organ development. EC specificity are identified by both intrinsic and extrinsic cues, among which, parenchyma and organ-specific microenvironment are critical contributors. These extrinsic cues are, however, largely lost during ex vivo cultures. Read More

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http://dx.doi.org/10.1152/ajprenal.00069.2020DOI Listing

Sensitivity of urethral flow-evoked voiding reflexes decline with age in the rat: insights into age-related underactive bladder.

Am J Physiol Renal Physiol 2020 Jun 4;318(6):F1430-F1440. Epub 2020 May 4.

Department of Biomedical Engineering, Florida International University, Miami, Florida.

The prevalence of underactive bladder (UAB) increases with age, suggesting a link between age-related processes and lower urinary tract (LUT) symptoms; however, the underlying mechanisms of age-related UAB are poorly understood. Understanding how aging affects LUT reflexes may help in the development of new treatments by identifying mechanistic targets. In this work, we studied the relationship between age and systems-level function of the LUT and tested the hypothesis that aging is related to weakening of reflexes that control voiding. Read More

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http://dx.doi.org/10.1152/ajprenal.00475.2019DOI Listing

Differences in renal BMAL1 contribution to sodium homeostasis and blood pressure control in male and female mice.

Am J Physiol Renal Physiol 2020 Apr 27. Epub 2020 Apr 27.

Medicine, Nephrology; Biochemistry and Molecular Biology, University of Florida, United States.

The renal circadian clock has a major influence on the function of the kidney. Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL; or BMAL1) is a core clock protein and transcription factor that regulates the expression of nearly half of all genes. Using male and female kidney-specific cadherin BMAL1 knockout mice (KS-BMAL1 KO), we examined the role of renal distal segment BMAL1 in blood pressure control and solute handling. Read More

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http://dx.doi.org/10.1152/ajprenal.00014.2020DOI Listing

Purinergic P2X receptor, purinergic P2X receptor, and angiotensin II type 1 receptor interactions in the regulation of renal afferent arterioles in angiotensin II-dependent hypertension.

Am J Physiol Renal Physiol 2020 Jun 20;318(6):F1400-F1408. Epub 2020 Apr 20.

Department of Physiology and Hypertension and Renal Center of Excellence, Tulane University Health Science Center, New Orleans, Louisiana.

In ANG II-dependent hypertension, ANG II activates ANG II type 1 receptors (ATRs), elevating blood pressure and increasing renal afferent arteriolar resistance (AAR). The increased arterial pressure augments interstitial ATP concentrations activating purinergic P2X receptors (P2XRs) also increasing AAR. Interestingly, P2XR and P2XR inhibition reduces AAR to the normal range, raising the conundrum regarding the apparent disappearance of ATR influence. Read More

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http://dx.doi.org/10.1152/ajprenal.00602.2019DOI Listing

Stimulation of the pelvic nerve increases bladder capacity in the PGE cat model of overactive bladder.

Am J Physiol Renal Physiol 2020 Jun 20;318(6):F1357-F1368. Epub 2020 Apr 20.

Department of Biomedical Engineering, Duke University, Durham, North Carolina.

Selective electrical stimulation of the pudendal nerve exhibits promise as a potential therapy for treating overactive bladder (OAB) across species (rats, cats, and humans). More recently, pelvic nerve (PelN) stimulation was demonstrated to improve cystometric bladder capacity in a PGE rat model of OAB. However, PelN stimulation in humans or in an animal model that is more closely related to humans has not been explored. Read More

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http://dx.doi.org/10.1152/ajprenal.00068.2020DOI Listing

Genetic ablation of SLK exacerbates glomerular injury in adriamycin nephrosis in mice.

Am J Physiol Renal Physiol 2020 Jun 20;318(6):F1377-F1390. Epub 2020 Apr 20.

Departments of Medicine and Physiology, McGill University Health Centre Research Institute, McGill University, Montreal, Quebec, Canada.

Ste20-like kinase SLK is critical for embryonic development and may play an important role in wound healing, muscle homeostasis, cell migration, and tumor growth. Mice with podocyte-specific deletion of SLK show albuminuria and damage to podocytes as they age. The present study addressed the role of SLK in glomerular injury. Read More

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http://dx.doi.org/10.1152/ajprenal.00028.2020DOI Listing

Intradialytic acid-base changes and organic anion production during high versus low bicarbonate hemodialysis.

Am J Physiol Renal Physiol 2020 Jun 20;318(6):F1418-F1429. Epub 2020 Apr 20.

Department of Medicine, Albert Einstein College of Medicine, Bronx, New York.

The use of high dialysate bicarbonate for hemodialysis in end-stage renal disease is associated with increased mortality, but potential physiological mediators are poorly understood. Alkalinization due to high dialysate bicarbonate may stimulate organic acid generation, which could lead to poor outcomes. Using measurements of β-hydroxybutyrate (BHB) and lactate, we quantified organic anion (OA) balance in two single-arm studies comparing high and low bicarbonate prescriptions. Read More

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http://dx.doi.org/10.1152/ajprenal.00036.2020DOI Listing

Epoxyeicosatrienoic acid metabolites inhibit Kir4.1/Kir5.1 in the distal convoluted tubule.

Am J Physiol Renal Physiol 2020 Jun 20;318(6):F1369-F1376. Epub 2020 Apr 20.

Department of Pharmacology, New York Medical College, Valhalla, New York.

Cytochrome -450 (Cyp) epoxygenase-dependent metabolites of arachidonic acid (AA) have been shown to inhibit renal Na transport, and inhibition of Cyp-epoxygenase is associated with salt-sensitive hypertension. We used the patch-clamp technique to examine whether Cyp-epoxygenase-dependent AA metabolites inhibited the basolateral 40-pS K channel (Kir4.1/Kir5. Read More

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http://dx.doi.org/10.1152/ajprenal.00018.2020DOI Listing

Integrin-β is required for the renal cystogenesis caused by ciliary defects.

Am J Physiol Renal Physiol 2020 May 20;318(5):F1306-F1312. Epub 2020 Apr 20.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.

Defects in the function of primary cilia are commonly associated with the development of renal cysts. On the other hand, the intact cilium appears to contribute a cystogenic signal whose effectors remain unclear. As integrin-β is required for the cystogenesis caused by the deletion of the polycystin 1 gene, we asked whether it would be similarly important in the cystogenetic process caused by other ciliary defects. Read More

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http://dx.doi.org/10.1152/ajprenal.00070.2020DOI Listing

Urine cytokines as biomarkers for diagnosing interstitial cystitis/bladder pain syndrome and mapping its clinical characteristics.

Am J Physiol Renal Physiol 2020 Jun 13;318(6):F1391-F1399. Epub 2020 Apr 13.

Department of Urology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan.

The objective of the present study was to investigate the diagnostic values of urine cytokines in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) and to identify their correlations with clinical characteristics. Urine samples were collected from 127 patients with IC/BPS [European Society for the Study of Interstitial Cystitis (ESSIC) types 1 and 2] and 28 controls. Commercially available multiplex immunoassays (MILLIPLEX map kits) were used to analyze 31 targeted cytokines. Read More

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http://dx.doi.org/10.1152/ajprenal.00051.2020DOI Listing

Western diet induces renal artery endothelial stiffening that is dependent on the epithelial Na channel.

Am J Physiol Renal Physiol 2020 May 13;318(5):F1220-F1228. Epub 2020 Apr 13.

Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri.

Consumption of a Western diet (WD) induces central aortic stiffening that contributes to the transmittance of pulsatile blood flow to end organs, including the kidney. Our recent work supports that endothelial epithelial Na channel (EnNaC) expression and activation enhances aortic endothelial cell stiffening through reductions in endothelial nitric oxide (NO) synthase (eNOS) and bioavailable NO that result in inflammatory and oxidant responses and perivascular fibrosis. However, the role that EnNaC activation has on endothelial responses in the renal circulation remains unknown. Read More

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http://dx.doi.org/10.1152/ajprenal.00517.2019DOI Listing

Resuscitation with PEGylated carboxyhemoglobin preserves renal cortical oxygenation and improves skeletal muscle microcirculatory flow during endotoxemia.

Am J Physiol Renal Physiol 2020 May 13;318(5):F1271-F1283. Epub 2020 Apr 13.

Department of Translational Physiology, Amsterdam University Medical Center Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

PEGylated carboxyhemoglobin (PEGHbCO), which has carbon monoxide-releasing properties and plasma expansion and oxygen-carrying properties, may improve both skeletal microcirculatory flow and renal cortical microcirculatory Po (CµPo) and, subsequently, limit endotoxemia-induced acute kidney injury. Anesthetized, ventilated Wistar albino rats ( = 44) underwent endotoxemic shock. CµPo was measured in exposed kidneys using a phosphorescence-quenching method. Read More

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http://dx.doi.org/10.1152/ajprenal.00513.2019DOI Listing

TCR+CD4-CD8- (double negative) T cells protect from cisplatin-induced renal epithelial cell apoptosis and acute kidney injury.

Am J Physiol Renal Physiol 2020 Apr 13. Epub 2020 Apr 13.

Medicine/Nephrology, Johns Hopkins University School of Medicine, United States.

Acute kidney injury (AKI) due to cisplatin is a significant problem that limits its use as an effective chemotherapeutic agent. TCR+CD4-CD8- double negative (DN) T cells constitute major T cell population in human and mouse kidney, express PD1 and protect from ischemic AKI. However, the pathophysiologic roles of DN T cells in cisplatin-induced AKI is unknown. Read More

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http://dx.doi.org/10.1152/ajprenal.00033.2020DOI Listing

Let's not take voiding for granted.

Authors:
Stephen A Zderic

Am J Physiol Renal Physiol 2020 Jun 13;318(6):F1313-F1314. Epub 2020 Apr 13.

Division of Urology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1152/ajprenal.00093.2020DOI Listing

Effects of extreme potassium stress on blood pressure and renal tubular sodium transport.

Am J Physiol Renal Physiol 2020 Jun 13;318(6):F1341-F1356. Epub 2020 Apr 13.

Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

We characterized mouse blood pressure and ion transport in the setting of commonly used rodent diets that drive K intake to the extremes of deficiency and excess. Male 129S2/Sv mice were fed either K-deficient, control, high-K basic, or high-KCl diets for 10 days. Mice maintained on a K-deficient diet exhibited no change in blood pressure, whereas K-loaded mice developed an ~10-mmHg blood pressure increase. Read More

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http://dx.doi.org/10.1152/ajprenal.00527.2019DOI Listing

Preeclampsia beyond pregnancy: long-term consequences for mother and child.

Am J Physiol Renal Physiol 2020 Jun 6;318(6):F1315-F1326. Epub 2020 Apr 6.

Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi.

Preeclampsia is defined as new-onset hypertension after the 20th wk of gestation along with evidence of maternal organ failure. Rates of preeclampsia have steadily increased over the past 30 yr, affecting ∼4% of pregnancies in the United States and causing a high economic burden (22, 69). The pathogenesis is multifactorial, with acknowledged contributions by placental, vascular, renal, and immunological dysfunction. Read More

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http://dx.doi.org/10.1152/ajprenal.00071.2020DOI Listing

Expression of XBP1s in B lymphocytes is critical for pristane-induced lupus nephritis in mice.

Am J Physiol Renal Physiol 2020 May 6;318(5):F1258-F1270. Epub 2020 Apr 6.

Department of Nephrology, Xijing Hospital, The Fourth Military Medical University of People's Liberation Army, Xi'an, China.

B lymphocyte hyperactivity plays a pathogenic role in systemic lupus erythematosus (SLE), and spliced X box-binding protein 1 (XBP1s) has been implicated in B cell maturation and differentiation. We hypothesized that blockade of the XBP1s pathway inhibits the B cell hyperactivity underlying SLE and lupus nephritis (LN) development. In the present study, we systematically evaluated the changes in B cell activation induced by the Xbp1 splicing inhibitor STF083010 in a pristane-induced lupus mouse model. Read More

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http://dx.doi.org/10.1152/ajprenal.00472.2019DOI Listing

Beneficial effect on podocyte number in experimental diabetic nephropathy resulting from combined atrasentan and RAAS inhibition therapy.

Am J Physiol Renal Physiol 2020 May 6;318(5):F1295-F1305. Epub 2020 Apr 6.

Department of Pathology, University of Washington, Seattle, Washington.

Podocyte loss and proteinuria are both key features of human diabetic nephropathy (DN). The leptin-deficient BTBR mouse strain with the mutation develops progressive weight gain, type 2 diabetes, and diabetic nephropathy that has many features of advanced human DN, including increased mesangial matrix, mesangiolysis, podocyte loss, and proteinuria. Selective antagonism of the endothelin-1 type A receptor (ETR) by atrasentan treatment in combination with renin-angiotensin-aldosterone system inhibition with losartan has been shown to have the therapeutic benefit of lowering proteinuria in patients with DN, but the underlying mechanism for this benefit is not well understood. Read More

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http://dx.doi.org/10.1152/ajprenal.00498.2019DOI Listing

Novel cell contact between podocyte microprojections and parietal epithelial cells analyzed by volume electron microscopy.

Am J Physiol Renal Physiol 2020 May 6;318(5):F1246-F1251. Epub 2020 Apr 6.

Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.

Podocytes are highly specialized cells with a clear cell polarity. It is known that in health and disease, microvilli protrude from the apical surface of the podocytes into the urinary space. As a basis to better understand the podocyte microprojections/microvilli, the present study analyzed their spatial localization, extension, and contact site with parietal epithelial cells (PECs). Read More

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http://dx.doi.org/10.1152/ajprenal.00097.2020DOI Listing

Chloroquine attenuates lithium-induced NDI and proliferation of renal collecting duct cells.

Am J Physiol Renal Physiol 2020 May 6;318(5):F1199-F1209. Epub 2020 Apr 6.

Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.

Lithium is widely used in psychiatry as the golden standard for more than 60 yr due to its effectiveness. However, its adverse effect has been limiting its long-term use in clinic. About 40% of patients taking lithium develop nephrogenic diabetes insipidus (NDI). Read More

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http://dx.doi.org/10.1152/ajprenal.00478.2019DOI Listing

Effect of caloric restriction on phosphate metabolism and uremic vascular calcification.

Am J Physiol Renal Physiol 2020 May 6;318(5):F1188-F1198. Epub 2020 Apr 6.

Department of Animal Medicine and Surgery, University of Cordoba, Campus Universitario Rabanales, Cordoba, Spain.

Caloric restriction (CR) is known to have multiple beneficial effects on health and longevity. To study the effect of CR on phosphorus metabolism and vascular calcification (VC), rats were fed normal or restricted calories (67% of normal). The phosphorus content of the diets was adjusted to provide equal phosphorus intake independent of the calories ingested. Read More

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http://dx.doi.org/10.1152/ajprenal.00009.2020DOI Listing

Metformin arrests the progression of established kidney disease in the subtotal nephrectomy model of chronic kidney disease.

Am J Physiol Renal Physiol 2020 May 6;318(5):F1229-F1236. Epub 2020 Apr 6.

Renal Pathophysiology Laboratory, Investigation on Diabetes Complications, Faculty of Medical Sciences, State University of Campinas, Campinas, São Paulo, Brazil.

Metformin, an AMP-activated protein kinase (AMPK) activator, has been shown in previous studies to reduce kidney fibrosis in different models of experimental chronic kidney disease (CKD). However, in all of these studies, the administration of metformin was initiated before the establishment of renal disease, which is a condition that does not typically occur in clinical settings. The aim of the present study was to investigate whether the administration of metformin could arrest the progression of established renal disease in a well-recognized model of CKD, the subtotal kidney nephrectomy (Nx) model. Read More

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http://dx.doi.org/10.1152/ajprenal.00539.2019DOI Listing

Potential risk of the kidney vulnerable to novel coronavirus 2019 infection.

Am J Physiol Renal Physiol 2020 May 30;318(5):F1136-F1137. Epub 2020 Mar 30.

Department of Nephrology and Laboratory of Kidney Disease, Hunan Provincial People's Hospital, Hunan Normal University, Changsha, China.

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http://dx.doi.org/10.1152/ajprenal.00085.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191387PMC

Transplanted senescent renal scattered tubular-like cells induce injury in the mouse kidney.

Am J Physiol Renal Physiol 2020 May 30;318(5):F1167-F1176. Epub 2020 Mar 30.

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.

Cellular senescence, a permanent arrest of cell proliferation, is characterized by a senescence-associated secretory phenotype (SASP), which reinforces senescence and exerts noxious effects on adjacent cells. Recent studies have suggested that transplanting small numbers of senescent cells suffices to provoke tissue inflammation. We hypothesized that senescent cells can directly augment renal injury. Read More

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http://dx.doi.org/10.1152/ajprenal.00535.2019DOI Listing

Hypertension induces glomerulosclerosis in phospholipase C-ε1 deficiency.

Am J Physiol Renal Physiol 2020 May 30;318(5):F1177-F1187. Epub 2020 Mar 30.

Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan.

Loss-of-function mutations in phospholipase C-ε1 (PLCE1) have been detected in patients with nephrotic syndrome, but other family members with the same mutation were asymptomatic, suggesting additional stressor are required to cause the full phenotype. Consistent with these observations, we determined that global -deficient mice have histologically normal glomeruli and no albuminuria at baseline. Angiotensin II (ANG II) is known to induce glomerular damage in genetically susceptible individuals. Read More

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http://dx.doi.org/10.1152/ajprenal.00541.2019DOI Listing

Uric acid and inflammation in kidney disease.

Am J Physiol Renal Physiol 2020 Jun 30;318(6):F1327-F1340. Epub 2020 Mar 30.

Division of Nephrology, Department of Internal Medicine, Kyung Hee University, College of Medicine, Seoul, Republic of Korea.

Asymptomatic hyperuricemia is frequently observed in patients with kidney disease. Although a substantial number of epidemiologic studies have suggested that an elevated uric acid level plays a causative role in the development and progression of kidney disease, whether hyperuricemia is simply a result of decreased renal excretion of uric acid or is a contributor to kidney disease remains a matter of debate. Over the last two decades, multiple experimental studies have expanded the knowledge of the biological effects of uric acid beyond its role in gout. Read More

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http://dx.doi.org/10.1152/ajprenal.00272.2019DOI Listing

Effects of uric acid dysregulation on the kidney.

Am J Physiol Renal Physiol 2020 May 30;318(5):F1252-F1257. Epub 2020 Mar 30.

Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin.

Recently, research has redirected its interests in uric acid (UA) from gout, an inflammatory disease in joints, to groups of closely interrelated pathologies associated with cardiovascular and kidney dysfunction. Many epidemiological, clinical, and experimental studies have shown that UA may play a role in the pathophysiology of the cardiorenal syndrome continuum; however, it is still unclear if it is a risk factor or a causal role. Hyperuricemia has been well studied in the past two decades, revealing mechanistic insights into UA homeostasis. Read More

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http://dx.doi.org/10.1152/ajprenal.00066.2020DOI Listing

Comprehensive assessment of mitochondrial respiratory function in freshly isolated nephron segments.

Am J Physiol Renal Physiol 2020 May 30;318(5):F1237-F1245. Epub 2020 Mar 30.

Oxidative Stress and Disease Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana.

Changes in mitochondrial function are central to many forms of kidney disease, including acute injury, diabetic nephropathy, hypertension, and chronic kidney diseases. As such, there is an increasing need for reliable and fast methods for assessing mitochondrial respiratory function in renal cells. Despite being indispensable for many mechanistic studies, cultured cells or isolated mitochondria, however, often do not recapitulate in vivo or close to in vivo situations. Read More

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http://dx.doi.org/10.1152/ajprenal.00031.2020DOI Listing

Distinct functions of megalin and cubilin receptors in recovery of normal and nephrotic levels of filtered albumin.

Am J Physiol Renal Physiol 2020 May 23;318(5):F1284-F1294. Epub 2020 Mar 23.

Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

Proximal tubule (PT) cells express a single saturable albumin-binding site whose affinity matches the estimated tubular concentration of albumin; however, albumin uptake capacity is greatly increased under nephrotic conditions. Deciphering the individual contributions of megalin and cubilin to the uptake of normal and nephrotic levels of albumin is impossible in vivo, as knockout of megalin in mice globally disrupts PT endocytic uptake. We quantified concentration-dependent albumin uptake in an optimized opossum kidney cell culture model and fit the kinetic profiles to identify albumin-binding affinities and uptake capacities. Read More

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http://dx.doi.org/10.1152/ajprenal.00030.2020DOI Listing

Dual blockade of protease-activated receptor 1 and 2 additively ameliorates diabetic kidney disease.

Am J Physiol Renal Physiol 2020 May 23;318(5):F1067-F1073. Epub 2020 Mar 23.

Division of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Sciences and Faculty of Pharmaceutical Sciences, Sendai, Japan.

Protease-activated receptors (PARs) are coagulation protease targets, and they increase expression of inflammatory cytokines and chemokines in various diseases. Of all PARs, previous reports have shown that PAR1 or PAR2 inhibition is protective against diabetic glomerular injury. However, how PAR1 and PAR2 cooperatively contribute to diabetic kidney disease (DKD) pathogenesis and whether dual blockade of PARs is more effective in DKD remain elusive. Read More

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http://dx.doi.org/10.1152/ajprenal.00595.2019DOI Listing

Increased fibrotic signaling in a murine model for intra-arterial contrast-induced acute kidney injury.

Am J Physiol Renal Physiol 2020 May 23;318(5):F1210-F1219. Epub 2020 Mar 23.

Vascular and Interventional Radiology Translational Laboratory, Department of Radiology, Mayo Clinic, Rochester, Minnesota.

Contrast-induced acute kidney injury (CI-AKI) is a vexing problem, and more than 70 million patients undergo studies using iodinated contrast. The molecular mechanisms responsible for CI-AKI are poorly understood. The goal of the present article was to determine the role of transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog (SMAD)3 and associated collagen expression in a murine model of intra-arterial CI-AKI. Read More

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http://dx.doi.org/10.1152/ajprenal.00004.2020DOI Listing

An enigma: does a high-protein diet accelerate renal damage in humans? Lessons from diabetic animal models.

Am J Physiol Renal Physiol 2020 Apr 16;318(4):F979-F981. Epub 2020 Mar 16.

Department of Pathology and Medicine, Northwestern University, Chicago, Illinois.

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http://dx.doi.org/10.1152/ajprenal.00076.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191452PMC

Combinatorial expression of claudins in the proximal renal tubule and its functional consequences.

Am J Physiol Renal Physiol 2020 May 16;318(5):F1138-F1146. Epub 2020 Mar 16.

Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas.

The proximal renal tubule (PT) is characterized by a highly conductive paracellular pathway, which contributes to a significant amount of solute and water reabsorption by the kidney. Claudins are tight junction proteins that, in part, determine the paracellular permeability of epithelia. In the present study, we determined the expression pattern of the major PT claudins. Read More

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http://dx.doi.org/10.1152/ajprenal.00057.2019DOI Listing

Pathophysiology of unilateral ischemia-reperfusion injury: importance of renal counterbalance and implications for the AKI-CKD transition.

Am J Physiol Renal Physiol 2020 May 16;318(5):F1086-F1099. Epub 2020 Mar 16.

Renal Section, Department of Medicine, Edward Hines Jr. Veterans Administration Hospital, Hines, Illinois.

Unilateral ischemia-reperfusion (UIR) injury leads to progressive renal atrophy and tubulointerstitial fibrosis (TIF) and is commonly used to investigate the pathogenesis of the acute kidney injury-chronic kidney disease transition. Although it is well known that contralateral nephrectomy (CNX), even 2 wk post-UIR injury, can improve recovery, the physiological mechanisms and tubular signaling pathways mediating such improved recovery remain poorly defined. Here, we examined the renal hemodynamic and tubular signaling pathways associated with UIR injury and its reversal by CNX. Read More

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http://dx.doi.org/10.1152/ajprenal.00590.2019DOI Listing

Meprin-β activity modulates the β-catalytic subunit of protein kinase A in ischemia-reperfusion-induced acute kidney injury.

Am J Physiol Renal Physiol 2020 May 16;318(5):F1147-F1159. Epub 2020 Mar 16.

Department of Biology, North Carolina A&T State University, Greensboro, North Carolina.

Meprin metalloproteases have been implicated in the progression of kidney injury. Previous work from our group has shown that meprins proteolytically process the catalytic subunit of protein kinase A (PKA-C), resulting in decreased PKA-C kinase activity. The goal of the present study was to determine the PKA-C isoforms impacted by meprin-β and whether meprin-β expression affects downstream mediators of the PKA signaling pathway in ischemia-reperfusion (IR)-induced kidney injury. Read More

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http://dx.doi.org/10.1152/ajprenal.00571.2019DOI Listing

UT-A1/A3 knockout mice show reduced fibrosis following unilateral ureteral obstruction.

Am J Physiol Renal Physiol 2020 May 16;318(5):F1160-F1166. Epub 2020 Mar 16.

Renal Division, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia.

Renal fibrosis is a major contributor to the development and progression of chronic kidney disease. A low-protein diet can reduce the progression of chronic kidney disease and reduce the development of renal fibrosis, although the mechanism is not well understood. Urea reabsorption into the inner medulla is regulated by inner medullary urea transporter (UT)-A1 and UT-A3. Read More

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http://dx.doi.org/10.1152/ajprenal.00008.2020DOI Listing

Ubiquitination of renal ENaC subunits in vivo.

Am J Physiol Renal Physiol 2020 May 16;318(5):F1113-F1121. Epub 2020 Mar 16.

Department of Physiology and Biophysics, Weill-Cornell Medical College, New York, New York.

Ubiquitination of the epithelial Na channel (ENaC) in epithelial cells may influence trafficking and hormonal regulation of the channels. We assessed ENaC ubiquitination (ub-ENaC) in mouse and rat kidneys using affinity beads to capture ubiquitinated proteins from tissue homogenates and Western blot analysis with anti-ENaC antibodies. Ub-αENaC was observed primarily as a series of proteins of apparent molecular mass of 40-70 kDa, consistent with the addition of variable numbers of ubiquitin molecules primarily to the NH-terminal cleaved fragment (~30 kDa) of the subunit. Read More

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http://dx.doi.org/10.1152/ajprenal.00609.2019DOI Listing

High-fructose corn syrup-sweetened soft drink consumption increases vascular resistance in the kidneys at rest and during sympathetic activation.

Am J Physiol Renal Physiol 2020 Apr 16;318(4):F1053-F1065. Epub 2020 Mar 16.

Center for Research and Education in Special Environments, Department of Exercise and Nutrition Sciences, University at Buffalo, Buffalo, New York.

We first tested the hypothesis that consuming a high-fructose corn syrup (HFCS)-sweetened soft drink augments kidney vasoconstriction to sympathetic stimulation compared with water (). In a second study, we examined the mechanisms underlying these observations (). In , 13 healthy adults completed a cold pressor test, a sympathoexcitatory maneuver, before (preconsumption) and 30 min after drinking 500 mL of decarbonated HFCS-sweetened soft drink or water (postconsumption). Read More

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http://dx.doi.org/10.1152/ajprenal.00374.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191446PMC

ELABELA antagonizes intrarenal renin-angiotensin system to lower blood pressure and protects against renal injury.

Am J Physiol Renal Physiol 2020 May 16;318(5):F1122-F1135. Epub 2020 Mar 16.

Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah.

Emerging evidence has demonstrated that (pro)renin receptor (PRR)-mediated activation of intrarenal renin-angiotensin system (RAS) plays an essential role in renal handling of Na and water balance and blood pressure. The present study tested the possibility that the intrarenal RAS served as a molecular target for the protective action of ELABELA (ELA), a novel endogenous ligand of apelin receptor, in the distal nephron. By RNAscope and immunofluorescence, mRNA and protein expression of endogenous ELA was consistently localized to the collecting duct (CD). Read More

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http://dx.doi.org/10.1152/ajprenal.00606.2019DOI Listing

Canagliflozin reduces cisplatin uptake and activates Akt to protect against cisplatin-induced nephrotoxicity.

Am J Physiol Renal Physiol 2020 Apr 9;318(4):F1041-F1052. Epub 2020 Mar 9.

Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta University, Augusta, Georgia.

Cisplatin is a widely used chemotherapy drug with notorious nephrotoxicity. Na-glucose cotransporter 2 inhibitors are a class of novel antidiabetic agents that may have other effects in the kidneys besides blood glucose control. In the present study, we demonstrated that canagliflozin significantly attenuates cisplatin-induced nephropathy in C57BL/6 mice and suppresses cisplatin induced renal proximal tubular cell apoptosis in vitro. Read More

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http://dx.doi.org/10.1152/ajprenal.00512.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7191450PMC