Calcineurin Inhibitors: A Double-Edge Sword.
Abstract Recently, research has directed its interests into identifying molecular pathways implicated in calcineurin inhibitor (CNI)-induced renal fibrosis. An emerging body of studies investigating calcineurin (CnA) activity has identified distinct actions of two main ubiquitously expressed isoforms: CnAα and CnAβ. CNIs have the capacity to inhibit both of these CnA isoforms. In the kidney, CnAα is required for development, whereas CnAβ predominantly modulates the immune response and glomerular hypertrophic signaling powered by activation of the transcription factor, Nuclear Factor of Activa...
Source: American Journal of Physiology. Renal Physiology - November 23, 2020 Category: Physiology Authors: Ume AC, Wenegieme TY, Williams CR Tags: Am J Physiol Renal Physiol Source Type: research

CD4+ T Cells cause Renal & Placental Mitochondrial Oxidative Stress as mechanisms of hypertension in response to placental ischemia.
CD4+ T Cells cause Renal & Placental Mitochondrial Oxidative Stress as mechanisms of hypertension in response to placental ischemia. Am J Physiol Renal Physiol. 2020 Nov 16;: Authors: Deer E, Reeve KE, Amaral LM, Vaka VR, Franks M, Campbell N, Fitzgerald S, Herrock OT, Ibrahim T, Cornelius DC, LaMarca BD Abstract The Reduced Uterine Perfusion Pressure (RUPP) rat model and normal pregnant (NP) rat recipients of RUPP CD4+T cells recapitulate many characteristics of preeclampsia (PE) such as hypertension and oxidative stress. We have shown an important hypertensive role for NK cells to cause mitochon...
Source: American Journal of Physiology. Renal Physiology - November 16, 2020 Category: Physiology Authors: Deer E, Reeve KE, Amaral LM, Vaka VR, Franks M, Campbell N, Fitzgerald S, Herrock OT, Ibrahim T, Cornelius DC, LaMarca BD Tags: Am J Physiol Renal Physiol Source Type: research

Connexin 43 is differentially distributed within renal vasculature and mediates profibrotic differentiation in medullary fibroblasts.
Abstract Connexins (Cxs) form gap junctions for intercellular exchange of inorganic ions and messenger molecules. In the kidney, Cxs play essential roles within its compartments, but data on the precise cellular localization and cell type-related function of their isoforms are scarce. We have tested whether Cx43 distribution is restricted to vascular and interstitial cells and whether medullary fibroblasts express Cx43 to coordinate profibrotic signaling. Confocal immunofluorescence techniques, ultrastructural labeling, and functional studies in cell culture were performed. Cx43 was chiefly expressed in the vascul...
Source: American Journal of Physiology. Renal Physiology - November 16, 2020 Category: Physiology Authors: Xu Y, Hu J, Yilmaz DE, Bachmann S Tags: Am J Physiol Renal Physiol Source Type: research

Pharmacological inhibition of Vanin-1 is not protective in models of acute and chronic kidney disease.
Abstract Oxidative stress is a key concept in basic, translational and clinical research to understand the pathophysiology of various disorders, including cardiovascular and renal diseases. While attempts to directly reduce oxidative stress with redox-active substances have until now largely failed to prove clinical benefit, indirect approaches to combat oxidative stress enzymatically gain further attention as potential therapeutic strategies. The pantetheinase Vanin-1 is expressed on kidney proximal tubular cells and its reaction product cysteamine is described to negatively affect redox homeostasis by inhibiting...
Source: American Journal of Physiology. Renal Physiology - November 16, 2020 Category: Physiology Authors: Unterschemmann K, Ehrmann A, Herzig I, Andreevski AL, Lustig K, Schmeck C, Eitner F, Grundmann M Tags: Am J Physiol Renal Physiol Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Renal Physiol. 2020 Nov 01;319(5):F863 Authors: PMID: 33141611 [PubMed] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - November 1, 2020 Category: Physiology Tags: Am J Physiol Renal Physiol Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Renal Physiol. 2020 Nov 01;319(5):F864 Authors: PMID: 33141612 [PubMed] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - November 1, 2020 Category: Physiology Tags: Am J Physiol Renal Physiol Source Type: research

The Complicated Role of Mitochondria in the Podocyte.
Abstract Mitochondria play a complex role in maintaining cellular function including ATP generation, generation of biosynthetic precursors for macromolecules, maintenance of redox homeostasis and metabolic waste management. Although, the contribution of mitochondrial function in various kidney diseases has been studied, there are still avenues that need to be explored under healthy and diseased conditions. Mitochondrial damage and dysfunction have been implicated in experimental models of podocytopathy as well as in humans with glomerular diseases resulting from podocyte dysfunction. Specifically, in the podocyte,...
Source: American Journal of Physiology. Renal Physiology - October 19, 2020 Category: Physiology Authors: Gujarati NA, Vasquez JM, Bogenhagen DF, Mallipattu SK Tags: Am J Physiol Renal Physiol Source Type: research

Circadian variation in renal blood flow and kidney function in healthy volunteers monitored using non-invasive magnetic resonance imaging.
In conclusion, total renal blood flow and kidney function, as estimated from excretion of electrolytes and waste products, display profound circadian variations, whereas intrarenal oxygenation displays significantly less circadian variation. PMID: 33073586 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - October 19, 2020 Category: Physiology Authors: Eckerbom P, Hansell P, Cox EF, Buchanan CE, Weis J, Palm F, Francis ST, Liss P Tags: Am J Physiol Renal Physiol Source Type: research

Mitochondrial Dysfunction and the AKI to CKD Transition.
Abstract Acute kidney injury (AKI) has been widely recognized as an important risk factor for the occurrence and development of chronic kidney disease (CKD). Even milder AKI has adverse consequences and could progress to renal fibrosis, which is the ultimate common pathway for various terminal kidney diseases. Thus, it is urgent to develop a strategy to hinder the transition from AKI to CKD. Some molecular mechanisms of AKI to CKD transition have been revealed, such as nephron loss, cell cycle arrest, persistent inflammation, endothelial injury with vascular rarefaction and epigenetic changes. Previous studies hav...
Source: American Journal of Physiology. Renal Physiology - October 19, 2020 Category: Physiology Authors: Jiang M, Bai M, Lei J, Xie Y, Xu S, Jia Z, Zhang A Tags: Am J Physiol Renal Physiol Source Type: research

CDKL5: a promising new therapeutic target for acute kidney injury?
PMID: 33073588 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - October 19, 2020 Category: Physiology Authors: de Caestecker MP Tags: Am J Physiol Renal Physiol Source Type: research

Using Best Subsets Regression to Identify Clinical Characteristics and Biomarkers Associated with Sepsis-Associated Acute Kidney Injury.
CONCLUSIONS: Using best subsets regression, we identified common clinical characteristics and biomarkers associated with sepsis-associated AKI. These variables may be especially relevant in the pathogenesis of sepsis-associated AKI. PMID: 33044866 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - October 12, 2020 Category: Physiology Authors: Kwong YD, Mehta K, Miaskowski C, Zhuo H, Yee K, Jauregui A, Ke S, Deiss T, Abbott J, Kangelaris KN, Sinha P, Hendrickson CM, Gomez A, Leligdowicz A, Matthay MA, Calfee CS, Liu KD Tags: Am J Physiol Renal Physiol Source Type: research

Involvement of the CDKL5-SOX9 signaling axis in rhabdomyolysis-associated acute kidney injury.
Abstract Acute kidney injury (AKI) is a common clinical syndrome associated with adverse short and long-term sequelae. Renal tubular epithelial cell (RTECs) dysfunction and cell death are among the key pathological features of AKI. Diverse systemic and localized stress conditions such as sepsis, rhabdomyolysis, cardiac surgery, and nephrotoxic drugs can trigger RTEC dysfunction. Through an unbiased RNAi screen, we recently identified cyclin-dependent kinase-like 5 (Cdkl5) also known as serine/threonine kinase 9 as a critical regulator of RTEC dysfunction associated with nephrotoxic and ischemia-associated AKI. In ...
Source: American Journal of Physiology. Renal Physiology - October 12, 2020 Category: Physiology Authors: Kim JY, Bai Y, Jayne LA, Cianciolo RE, Bajwa A, Pabla NS Tags: Am J Physiol Renal Physiol Source Type: research

A New Mechanism for the Sex Differences in Angiotensin II-Induced Hypertension---The Role of Macula Densa NOS1 β-Mediated Tubuloglomerular Feedback.
In conclusion, macula densa NOS1β-mediated TGF is a novel and important mechanism for the sex differences in Angiotensin II-Induced hypertension. PMID: 33044868 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - October 12, 2020 Category: Physiology Authors: Zhang J, Qu L, Wei J, Jiang S, Xu L, Wang L, Cheng F, Jiang K, Buggs J, Liu R Tags: Am J Physiol Renal Physiol Source Type: research

Intrarenal oxygenation determines kidney function during the recovery from an ischemic insult.
alm F Abstract Acute kidney injury (AKI) is a significant clinical problem associated with poor outcome. The kidney, due to its inhomogeneous blood flow, is particularly susceptible to changes in oxygen delivery and intrarenal hypoxia is a hallmark of AKI, and progression to chronic kidney disease. However, the role of intrarenal hypoxia per se in recovery from an ischemic insult is presently unclear. The present study was designed to investigate 1) the role of systemic hypoxia in the acute progression and recovery of AKI, and 2) if increased intrarenal oxygenation improves recovery from an ischemic insult. Anaest...
Source: American Journal of Physiology. Renal Physiology - October 12, 2020 Category: Physiology Authors: Nensén O, Hansell P, Palm F Tags: Am J Physiol Renal Physiol Source Type: research

Retromer is involved in epithelial sodium channel trafficking.
Abstract The epithelial sodium channel, ENaC, located at the apical membrane in many epithelia, is the rate-limiting step for sodium reabsorption. Tight regulation of the plasma membrane population of ENaC is required as hyper- or hypotension may result if too many or too few ENaCs are present. Endocytosed ENaC travels to the early endosome and is then either trafficked to the lysosome for degradation or recycled back to the plasma membrane. Recently, the retromer recycling complex, located at the early endosome, has been implicated in plasma membrane protein recycling pathways. We hypothesized that retromer is re...
Source: American Journal of Physiology. Renal Physiology - October 4, 2020 Category: Physiology Authors: Cheung TT, Geda AC, Ware AW, Rasulov SR, Tenci P, Hamilton KL, McDonald FJ Tags: Am J Physiol Renal Physiol Source Type: research

Class IIa HDAC inhibitor TMP195 alleviates lipopolysaccharide-induced acute kidney injury.
In this study, we explored the possible renoprotective effect of a selective class IIa HDAC inhibitor TMP195 in a murine model of SA-AKI induced by lipopolysaccharide (LPS). Administration of TMP195 significantly reduced increased serum creatinine and blood urea nitrogen levels and renal damage induced by LPS; this was coincident with reduced expression of HDAC4, a major isoform of class IIa HDACs, and elevated histone H3 acetylation. TMP195 treatment following LPS exposure also reduced renal tubular cell apoptosis and attenuated renal expression of NGAL and Kim-1, two biomarkers of tubular injury. Moreover, LPS exposure r...
Source: American Journal of Physiology. Renal Physiology - October 4, 2020 Category: Physiology Authors: Zhang W, Bayliss GP, Zhuang S Tags: Am J Physiol Renal Physiol Source Type: research

T-cell derived Extracellular Vesicles are elevated in essential HTN.
r U Abstract Extracellular vesicles (EVs) are novel mediators of cell-to-cell communication and appear to mediate the pathogenesis of hypertension (HTN). However, the mechanisms underlying the involvement of EVs in HTN remain unclear. The adaptive and innate immune systems (IS) play an important role affecting the kidney and vasculature in animal models of HTN. Evolving evidence shows that immune cell-derived EVs can modulate the IS in a paracrine fashion and therefore may mediate the effects of inflammation in the pathogenesis of HTN. Therefore, we aimed to understand if specific subtypes of leukocyte/immune-cell...
Source: American Journal of Physiology. Renal Physiology - October 4, 2020 Category: Physiology Authors: La Salvia S, Musante L, Lannigan J, Gigliotti J, Le TH, Erdbrügger U Tags: Am J Physiol Renal Physiol Source Type: research

Afferent Renal Innervation in Anti Thy1.1 Nephritis in Rats.
Abstract Afferent renal nerves exhibit a dual function controlling central sympathetic outflow via afferent electrical activity and influencing intrarenal immunological processes by releasing peptides such as calcitonin-gene-related peptide (CGRP). We tested the hypothesis that increased afferent (ARNA) and efferent renal nerve activity (RSNA) occur with augmented release of CGRP in anti-Thy1.1 nephritis, in which enhanced CGRP release exacerbates inflammation. Nephritis was induced in Sprague-Dawley rats by intravenous injection of OX-7 antibody (1.75 mg/kg), animals were investigated neurophysiologically, electr...
Source: American Journal of Physiology. Renal Physiology - October 4, 2020 Category: Physiology Authors: Rodionova K, Veelken R, Hilgers KF, Paulus EM, Linz P, Fischer MJM, Schenker M, Reeh PW, Tiegs G, Ott C, Schmieder RE, Schiffer M, Amann K, Ditting T Tags: Am J Physiol Renal Physiol Source Type: research

Protein kinase A catalytic- α and catalytic-β proteins have non-redundant regulatory functions.
Protein kinase A catalytic-α and catalytic-β proteins have non-redundant regulatory functions. Am J Physiol Renal Physiol. 2020 Oct 05;: Authors: Raghuram V, Salhadar K, Limbutara K, Park E, Yang CR, Knepper MA Abstract Vasopressin regulates osmotic water transport in the renal collecting duct by PKA-mediated control of the water channel aquaporin-2 (AQP2). Collecting duct principal cells express two seemingly redundant PKA catalytic subunits, PKA catalytic α (PKA-Cα) and PKA catalytic β (PKA-Cβ). To identify the roles of these two protein kinases, we carried out deep ...
Source: American Journal of Physiology. Renal Physiology - October 4, 2020 Category: Physiology Authors: Raghuram V, Salhadar K, Limbutara K, Park E, Yang CR, Knepper MA Tags: Am J Physiol Renal Physiol Source Type: research

The effect of angiotensin II on diabetic glomerular hyperpermeability: In vivo permeability studies in rats.
We examined the changes in the glomerular permeability after subcutaneous infusion of angiotensin II at 200 ng/kg/min for 7 days into male Wistar diabetic rats with 3 months of STZ-induced diabetes (i.e., blood glucose of approximately 20 mmoL/L). We also compared these changes with the effects on nondiabetic rats. The sieving coefficients (θ) for inert polydisperse Ficoll molecules, which had a radius of 10-90 Å, were measured in vivo. The θ for large Ficoll molecules was selectively enhanced after infusion of extended angiotensin II into both diabetic (θ for Ficoll70-90 Å = 0.00244 vs. 0.00079, P
Source: American Journal of Physiology. Renal Physiology - October 4, 2020 Category: Physiology Authors: Nalin N, Dhanhani AA, AlBawardi A, Sharma C, Chandran S, Yasin J, Bakoush O Tags: Am J Physiol Renal Physiol Source Type: research

SGLT2 inhibitors: Diabetic kidney disease and beyond.
PMID: 33017191 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - October 4, 2020 Category: Physiology Authors: Staruschenko A, Bhalla V, Rangaswami J Tags: Am J Physiol Renal Physiol Source Type: research

Sprr2f protects against renal injury by decreasing the level of reactive oxygen species in female mice.
Abstract Renal injury leads to chronic kidney disease for which women are not only more likely to be diagnosed with than men but have poorer outcomes as well. We have previously shown that expression of Sprr2f, a member of the Small Proline Rich Region (Sprr) gene family, is increased several hundred-fold after renal injury using a unilateral ureteral obstruction (UUO) mouse model. To better understand the role of Sprr2f in renal injury, we generated a Sprr2f knockout (Sprr2f-KO) mouse model using CRISPR-Cas9 technology. Sprr2f-KO female mice showed greater renal damage after UUO compared to wild type (Sprr2f-WT) ...
Source: American Journal of Physiology. Renal Physiology - October 4, 2020 Category: Physiology Authors: Huynh KM, Wong A, Wu B, Horschman M, Zhao H, Brooks JD Tags: Am J Physiol Renal Physiol Source Type: research

Cerebral blood flow regulation in end-stage kidney disease.
Abstract Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) patients experience an increased risk of cerebrovascular disease and cognitive dysfunction. Hemodialysis (HD), a major modality of renal replacement therapy in ESKD, can cause rapid changes in blood pressure, osmolality, and acid-base balance that collectively present a unique stress to the cerebral vasculature. This review presents an update regarding cerebral blood flow (CBF) regulation in CKD and ESKD, and how the maintenance of cerebral oxygenation may be compromised during HD. ESKD patients exhibit decreased cerebral oxygen delivery due...
Source: American Journal of Physiology. Renal Physiology - September 27, 2020 Category: Physiology Authors: Sprick JD, Nocera J, Hajjar I, O'Neill WC, Bailey JL, Park J Tags: Am J Physiol Renal Physiol Source Type: research

Salt-Sensitive Hypertension in Chronic Kidney Disease: Distal Tubular Mechanisms.
Abstract Chronic kidney disease (CKD) causes salt-sensitive hypertension that is often resistant to treatment and contributes to the progression of kidney injury and cardiovascular disease. A better understanding of the mechanisms contributing to salt-sensitive hypertension in CKD is essential to improve these outcomes. This review critically explores these mechanisms by focusing on how CKD affects distal nephron sodium (Na+) reabsorption. CKD causes glomerulotubular imbalance with reduced proximal Na+ reabsorption and increased distal Na+ delivery and reabsorption. Aldosterone secretion further contributes to dis...
Source: American Journal of Physiology. Renal Physiology - September 27, 2020 Category: Physiology Authors: Bovee DM, Cuevas CA, Zietse R, Danser AHJ, Mirabito Colafella KM, Hoorn EJ Tags: Am J Physiol Renal Physiol Source Type: research

Effects of Long-Term Intra-Dialytic Oral Nutrition and Exercise on Muscle Protein Homeostasis and Markers of Mitochondrial Content in Patients on Hemodialysis.
Abstract Patients with end-stage kidney disease (ESKD) on maintenance hemodialysis (MHD) commonly develop protein-energy wasting (PEW), a syndrome characterized by nutritional and metabolic abnormalities. Nutritional supplementation and exercise are recommended to prevent PEW. In a six-month prospective randomized, open-label, clinical trial, we reported that the combination of resistance exercise and nutritional supplementation does not have an additive effect on lean body mass measured by DEXA. In order to provide more mechanistic data, we performed a secondary analysis where we hypothesized that the combination...
Source: American Journal of Physiology. Renal Physiology - September 27, 2020 Category: Physiology Authors: Gamboa JL, Deger SM, Perkins BW, Mambungu C, Sha F, Mason OJ, Stewart TG, Ikizler TA Tags: Am J Physiol Renal Physiol Source Type: research

Sex-Differences in Solute Transport Along the Nephrons: Effects of Na+ Transport Inhibition.
Abstract Each day approximately 1.7kg of NaCl and 180L of water are reabsorbed by nephron segments in humans, with urinary excretion fine-tuned to meet homeostatic requirements. These tasks are coordinated by a spectrum of renal Na+ transporters. The goal of this study was to investigate the extent to which inhibitors of transepithelial Na+ transport (TNa) along the nephron alter urinary solute excretion and how those effects may vary between males and females. To accomplish that goal, we developed sex-specific multinephron models that represent detailed transcellular and paracellular transport processes along the...
Source: American Journal of Physiology. Renal Physiology - August 2, 2020 Category: Physiology Authors: Hu R, McDonough AA, Layton AT Tags: Am J Physiol Renal Physiol Source Type: research

Inflammatory mediators in the adipo-renal axis: leptin, adiponectin, and sICAM-1.
CONCLUSION: Both mediation analyses identified an inflammatory (leptin) and an anti-inflammatory (adiponectin) cytokine along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity. PMID: 32744085 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - August 2, 2020 Category: Physiology Authors: Hua Y, Herder C, Kalhoff H, Buyken AE, Esche J, Krupp D, Wudy SA, Remer T Tags: Am J Physiol Renal Physiol Source Type: research

Ventilatory and chronotropic incompetence during incremental and constant load exercise in end-stage renal disease: a comparative physiology study.
Abstract BACKGROUND: Aerobic capacity is impaired in end-stage renal disease (ESRD), reducing quality of life and longevity. Whilst determinants of maximal exercise intolerance are well defined, little is known of limitation during submaximal exercise. By comparing ESRD and healthy controls, the aim of this study was to characterise mechanisms of exercise intolerance in ESRD by assessing cardiopulmonary physiology at rest and during exercise. METHODS: Resting spirometry and echocardiography were performed in 20 ESRD participants and 20 healthy age and gender matched controls. Exercise tolerance was assessed w...
Source: American Journal of Physiology. Renal Physiology - August 2, 2020 Category: Physiology Authors: McGuire S, Horton EJ, Renshaw D, Chan K, Krishnan N, McGregor G Tags: Am J Physiol Renal Physiol Source Type: research

PF-06869206 is selective inhibitor of renal Pi transport: Evidence from in vitro and in vivo studies.
Abstract Plasma phosphate (Pi) levels are tightly controlled, and elevated plasma Pi levels are associated with an increased risk of cardiovascular complications and death. Two renal transport proteins mediate the majority of Pi reabsorption, the Na+-phosphate cotransporters Npt2a and Npt2c, with Npt2a accounting for 70-80% of Pi reabsorption. The aim of this study was to determine the in vitro effects of a novel Npt2a inhibitor (Npt2a-I, PF-06869206) in opossum kidney (OK) cells as well as determine its selectivity in vivo in Npt2a knockout (Npt2a-/-) mice. In OK cells, Npt2a-I caused dose-dependent reductions of...
Source: American Journal of Physiology. Renal Physiology - August 2, 2020 Category: Physiology Authors: Thomas L, Xue J, Tomilin VN, Pochynyuk OM, Dominguez Rieg JA, Rieg T Tags: Am J Physiol Renal Physiol Source Type: research

Despite initial recovery of GFR long-term renal functions deteriorate following short periods of unilateral ureteral obstruction.
In conclusion, several aspects of renal functions continue to deteriorate following reversal of relatively short periods of UUO despite the initial recovery in GFR. This might stimulate further research in this area and might have clinical implications in terms of determining the best time for intervention following acute ureteral obstruction and long-term monitoring of these individuals. PMID: 32744088 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - August 2, 2020 Category: Physiology Authors: Hammad FT, Al-Salam S, Hammad WF, Yasin J, Lubbad L Tags: Am J Physiol Renal Physiol Source Type: research

Corrigendum.
CORRIGENDUM. Am J Physiol Renal Physiol. 2020 Aug 01;319(2):F256 Authors: PMID: 32686976 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - July 21, 2020 Category: Physiology Tags: Am J Physiol Renal Physiol Source Type: research

Ultrasound measurement of change in kidney volume is a sensitive indicator of severity of renal parenchymal injury.
Abstract Non-invasive determination of the severity of parenchymal injury in acute kidney injury (AKI) remains challenging. Edema is an early pathological process following injury, which may correlate with changes in kidney volume. The goal of this study was to test the hypothesis that 'increases in kidney volume, measured in vivo using ultrasound correlate with the degree of renal parenchymal injury'. Ischemia reperfusion (IR) of varying length was utilized to produce graded tissue injury. We first determined 1) whether regional kidney volume in rats varied with the severity (0, 15, 30, 45 minutes) of warm bilate...
Source: American Journal of Physiology. Renal Physiology - July 19, 2020 Category: Physiology Authors: Crislip GR, Patel B, Mohamed R, Ray SC, Wei Q, Sun J, Polichnowski A, Sullivan JC, O'Connor PM Tags: Am J Physiol Renal Physiol Source Type: research

T95 Nucleophosmin Phosphorylation as a Novel Mediator and Marker of Regulated Cell Death in Acute Kidney Injury.
Abstract The function of site-specific phosphorylation of nucleophosmin (NPM), an essential Bax chaperone, in stress-induced cell death is unknown. We hypothesized that NPM threonine 95 (T95) phosphorylation both signals and promotes cell death. In resting cells, NPM exclusively resides in the nucleus and threonine 95 is non-phosphorylated. In contrast, phosphorylated T95 NPM (pNPM T95) accumulates in the cytosol after metabolic stress, in multiple human cancer cell lines following gamma radiation, and in post-ischemic human kidney tissue. Based on the T95 phosphorylation consensus sequence, we hypothesized that g...
Source: American Journal of Physiology. Renal Physiology - July 19, 2020 Category: Physiology Authors: Wang Z, Belghasem M, Salih E, Henderson J, Igwebuike C, Havasi A, Borkan SC Tags: Am J Physiol Renal Physiol Source Type: research

Non-esterified free fatty acids (NEFA) enhance the inflammatory response in renal tubules by inducing extracellular ATP release.
Abstract In proteinuric renal diseases, excessive plasma non-esterified free fatty acids (NEFA) bound to albumin can leak across damaged glomeruli to be reabsorbed by renal proximal tubular cells and cause inflammatory tubular cellsdamage by as yet unknown mechanisms. The present study was designed to investigate these mechanisms induced by palmitic acid (PA, one of NEFA) overload. Our results show that excess PA stimulates ATP release through the pannexin1 (Panx1) channel in human renal tubule epithelial cells (HK-2); increasing extracellular ATP (eATP) concentration approximately three-fold in comparison with co...
Source: American Journal of Physiology. Renal Physiology - July 19, 2020 Category: Physiology Authors: Sun H, Sun Z, Varghese Z, Guo Y, Moohread JF, Unwin RJ, Ruan XZ Tags: Am J Physiol Renal Physiol Source Type: research

ANO1 in urethral SMCs contributes to sex differences in urethral spontaneous tone.
Abstract Stress urinary incontinence (SUI) is more common in women than in men, and gender differences in anatomical structure and physiology have been suggested; however, the cellular and molecular mechanisms involved remain unclear. Spontaneous tone of urethra was proved to take the fundamental effect in preventing occurrence of SUI. We investigated whether the urethral spontaneous tone exhibited gender differences. Here, we isolated the urethral smooth muscle and detected the spontaneous tones in female mouse and women. No spontaneous tone was found in male mouse and men. Furthermore, caffeine excited more cont...
Source: American Journal of Physiology. Renal Physiology - July 19, 2020 Category: Physiology Authors: Chen D, Meng W, Shu L, Liu S, Gu Y, Wang X, Feng M Tags: Am J Physiol Renal Physiol Source Type: research

Therapeutic potential of muscle growth promoters in a stress urinary incontinence model.
In conclusion, bimagrumab was the most effective for increasing urethral pressure and continence by promoting injured EUS and pelvic floor muscle recovery. PMID: 32686522 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - July 19, 2020 Category: Physiology Authors: Yang J, Balog BM, Deng K, Hanzlicek B, Rietsch A, Kuang M, Hatakeyama S, Lach-Trifilieff E, Zhu H, Damaser MS Tags: Am J Physiol Renal Physiol Source Type: research

IL-10 treatment decreases blood pressure in male, but not female, spontaneously hypertensive rats.
In conclusion, despite male SHR having less IL-10 and IL-10 receptor expression in the kidney compared to females, exogenous IL-10 selectively decreased BP only in males. Furthermore, our data suggests that exogenous IL-10-induced decreases in BP in male SHR are not dependent on upregulating renal NOS activity. PMID: 32686523 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - July 19, 2020 Category: Physiology Authors: Gillis EE, Musall JB, Baban B, Sullivan JC Tags: Am J Physiol Renal Physiol Source Type: research

Phosphorylation of key podocyte proteins and the association with proteinuric kidney disease.
Abstract Podocyte dysfunction contributes to proteinuric chronic kidney disease. A number of key proteins are essential for podocyte function, including nephrin, podocin, CD2-associated protein (CD2AP), synaptopodin, and a-actinin-4 (ACTN4). Although most of these proteins were first identified through genetic studies associated with human kidney disease, subsequent studies have identified phosphorylation of these proteins as an important post-translational event that regulates their function. In this review, a brief overview of the function of these key podocyte proteins is provided. Second, the role of phosphory...
Source: American Journal of Physiology. Renal Physiology - July 19, 2020 Category: Physiology Authors: Feng D Tags: Am J Physiol Renal Physiol Source Type: research

Mitochondrial Transplantation by Intra-Arterial Injection for Acute Kidney Injury.
In this study, the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal ischemia-reperfusion injury (IRI) was investigated. Female Yorkshire pigs underwent percutaneous bilateral temporary occlusion of the renal arteries with balloon-catheters. Following 60 minutes ischemia, the balloon catheters were deflated and the animals received either autologous mitochondria suspended in vehicle or vehicle alone, delivered as a single bolus to the renal arteries. The injected mitochondria were rapidly taken up by the kidney and were distr...
Source: American Journal of Physiology. Renal Physiology - July 19, 2020 Category: Physiology Authors: Doulamis IP, Guariento A, Duignan T, Kido T, Orfany A, Saeed MY, Weixler VH, Blitzer D, Shin B, Snay ER, Inkster JAH, Packard AB, Zurakowski D, Rousselle T, Bajwa A, Parikh SM, Stillman IE, Del Nido PJ, McCully JD Tags: Am J Physiol Renal Physiol Source Type: research

Role of SIRT1 in HIV-associated kidney disease.
Abstract HIV infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We previously showed that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3 were increased in HIVAN kidneys. Here, we demonstrate the key role of SIRT1 deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in...
Source: American Journal of Physiology. Renal Physiology - July 12, 2020 Category: Physiology Authors: Wang X, Liu R, Zhang W, Hyink DP, Das GC, Das B, Li Z, Wang A, Yuan W, Klotman PE, Lee K, He JC Tags: Am J Physiol Renal Physiol Source Type: research

A novel distal convoluted tubule-specific Cre-recombinase driven by the NaCl cotransporter gene.
Abstract Cre-lox technology has revolutionized research in renal physiology by allowing site-specific genetic recombination in individual nephron segments. The distal convoluted tubule (DCT), consisting of distinct early (DCT1) and late (DCT2) segments, plays a central role in Na+ and K+ homeostasis. The only established Cre line targeting the DCT is Pvalb-Cre, which is limited by non-inducibility, activity along DCT1 only, and activity in neurons. Here, we report the characterization of the first Cre line specific to the entire DCT. CRISPR/Cas9 targeting was used to introduce a tamoxifen-inducible IRES-Cre-ERT2 c...
Source: American Journal of Physiology. Renal Physiology - July 12, 2020 Category: Physiology Authors: Cornelius RJ, Sharma A, Su XT, Guo JJ, McMahon JA, Ellison DH, McMahon AP, McCormick JA Tags: Am J Physiol Renal Physiol Source Type: research

Acetazolamide Causes Renal HCO3 ‾ Wasting but Inhibits Ammoniagenesis and Prevents the Correction of Metabolic Acidosis by the Kidney.
Acetazolamide Causes Renal HCO3‾ Wasting but Inhibits Ammoniagenesis and Prevents the Correction of Metabolic Acidosis by the Kidney. Am J Physiol Renal Physiol. 2020 Jul 13;: Authors: Alam P, Amlal S, Thakar CV, Amlal H Abstract Carbonic anhydrase (CAII) binds to the basolateral Na+: HCO3‾ cotransporter (NBCe1) and facilitates HCO3‾ reabsorption across the proximal tubule. However, whether the inhibition of CAII with acetazolamide (ACTZ) alters NBCe1 activity and interferes with ammoniagenesis pathway remains elusive. To address this issue, we compared the renal adaptation of rats t...
Source: American Journal of Physiology. Renal Physiology - July 12, 2020 Category: Physiology Authors: Alam P, Amlal S, Thakar CV, Amlal H Tags: Am J Physiol Renal Physiol Source Type: research

Hypertensive Female Sprague Dawley rats require an intact nitric oxide synthase system for compensatory increases in renal T regulatory cells.
This study provides insight into the mechanisms regulating renal Tregs and supports that an intact NOS system is crucial for female rats to have BP-related increases in renal Tregs. PMID: 32597687 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - June 28, 2020 Category: Physiology Authors: Ramirez LA, Gillis EE, Musall JB, Mohamed R, Snyder E, El-Marakby AA, Sullivan JC Tags: Am J Physiol Renal Physiol Source Type: research

Novel Catheter Design Enables Transurethral Catheterization of Male Mice.
Abstract The male mouse is underrepresented in research of the urinary tract due to the difficulty of transurethral catheterization. As a result, there is a lack of analysis of gender differences in urinary tract research. Here, we present a novel catheter design and technique that enables urethral catheterization of male mice. Our catheterization technique uses the resistance met at the level of the external urinary sphincter and prostate to guide the retraction, positioning, and advancement of the catheter into the urinary bladder. We have shown that this method can be used to reproducibly catheterize 12 male mi...
Source: American Journal of Physiology. Renal Physiology - May 27, 2020 Category: Physiology Authors: Lamanna OK, Hsieh MH, Forster CS Tags: Am J Physiol Renal Physiol Source Type: research

14-3-3 gamma, a novel regulator of the large-conductance Ca2+-activated K+ channels.
Abstract 14-3-3 gamma (γ) is a small protein regulating the target proteins through binding to the phosphorylated serine/threonine residues. Sequence analysis of large-conductance Ca2+-activated K+ (BK) channel revealed a putative 14-3-3 binding site in the C-terminal region. Our previous data showed that 14-3-3γ is widely expressed in the mouse kidney. We, therefore, hypothesized that 14-3-3γ has a novel role in the regulation of BK channel activity and protein expression. We first demonstrated the interaction of 14-3-3γ with BKα by co-immunoprecipitation. In HEK293 cells stably expr...
Source: American Journal of Physiology. Renal Physiology - May 27, 2020 Category: Physiology Authors: Chen S, Feng X, Chen X, Zhuang Z, Xiao J, Fu H, Klein JD, Wang XH, Hoover RS, Eaton DC, Cai H Tags: Am J Physiol Renal Physiol Source Type: research

The differential effects of low dose sacubitril and/or valsartan on renal disease in salt-sensitive hypertension.
Abstract Diuretics and renin-angiotensin system (RAAS) blockers are often insufficient to control the blood pressure (BP) in salt-sensitive (SS) subjects. Abundant data support the proposal that level of Atrial Natriuretic Peptide (ANP) may correlate with pathogenesis of SS hypertension. We hypothesized here that increasing ANP level with sacubitril, combined with RAAS blockage by valsartan, can be beneficial for alleviation of renal damage in a model of SS hypertension, the Dahl SS rat. To induce a BP increase, the rats were challenged with a high salt 4% NaCl diet for 21 days, and chronic administration of vehic...
Source: American Journal of Physiology. Renal Physiology - May 27, 2020 Category: Physiology Authors: Polina I, Domondon M, Fox R, Sudarikova A, Troncoso M, Vasileva V, Kashyrina Y, Beck Gooz M, Schibalski R, DeLeon-Pennell KY, Fitzgibbon WR, Ilatovskaya DV Tags: Am J Physiol Renal Physiol Source Type: research

NF- κB blockade during short-term L-NAME and salt overload strongly attenuates the late development of chronic kidney disease.
NF-κB blockade during short-term L-NAME and salt overload strongly attenuates the late development of chronic kidney disease. Am J Physiol Renal Physiol. 2020 May 28;: Authors: Carneiro Oliveira K, Fregnan Zambom FF, Albino AH, Costa Alarcon Arias S, Ferreira Ávila V, Dias Faustino V, Avancini Costa Malheiros DM, Olsen Saraiva Camara N, Kazue Fujihara C, Zatz R Abstract NO synthase inhibition by L-NAME plus high-salt diet (HS) is a model of Chronic Kidney Disease (CKD) characterized by marked hypertension and renal injury. With cessation of treatment, most of these changes subside, but pr...
Source: American Journal of Physiology. Renal Physiology - May 27, 2020 Category: Physiology Authors: Carneiro Oliveira K, Fregnan Zambom FF, Albino AH, Costa Alarcon Arias S, Ferreira Ávila V, Dias Faustino V, Avancini Costa Malheiros DM, Olsen Saraiva Camara N, Kazue Fujihara C, Zatz R Tags: Am J Physiol Renal Physiol Source Type: research

Renal ischemia alters expression of mitochondria-related genes and impairs mitochondrial structure and function in swine scattered tubular-like cells.
Abstract Scattered tubular-like cells (STCs) are dedifferentiated surviving tubular epithelial cells that repair neighboring injured cells. Experimental renal artery stenosis (RAS) impairs STC reparative potency by inducing mitochondrial injury, but the exact mechanisms of mitochondrial damage remains unknown. We hypothesized that RAS alters expression of mitochondria-related genes, contributing to mitochondrial structural damage and dysfunction in swine STCs. CD24+/CD133+ STCs were isolated from pig kidneys after 10 weeks of RAS or sham (n=3 each). mRNA sequencing was performed and nuclear-DNA (nDNA) encoded mito...
Source: American Journal of Physiology. Renal Physiology - May 27, 2020 Category: Physiology Authors: Farahani RA, Zhu XY, Tang H, Jordan KL, Lerman LO, Eirin A Tags: Am J Physiol Renal Physiol Source Type: research

Normal range urine albumin excretion associates with blood pressure and renal electrolyte handling in pregnancy.
CONCLUSIONS: At gestational week 29, urinary albumin excretion in the normal range associated with blood pressure and renal electrolyte handling independent of potential confounders. PMID: 32463729 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Renal Physiology)
Source: American Journal of Physiology. Renal Physiology - May 27, 2020 Category: Physiology Authors: Birukov A, Andersen MS, Jørgensen JS, Kitlen G, Rakova N, Nielsen JH, Andersen LB, Dechend R, Jensen BL Tags: Am J Physiol Renal Physiol Source Type: research

Monophosphoryl lipid A pretreatment suppresses sepsis- and LPS-induced proinflammatory cytokine production in medullary thick ascending limb.
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. Treatment with LPS for 3 h in vitro also increased MTAL TNF-α production. Sepsis and LPS increased MTAL TNF-α expression through activation of an MyD88-IRAK-1-ERK signaling pathway. Pretreatment with monophosphoryl lipid A (MPLA), a nontoxic immunomodulator that protects against bacterial infection, eliminated the sepsis- and LPS-induced increases in MTAL TNF-α production. The suppressive effect of MPLA on TNF-α was mediated through act...
Source: American Journal of Physiology. Renal Physiology - May 17, 2020 Category: Physiology Authors: Watts BA, Tamayo EH, Sherwood ER, Good DW Tags: Am J Physiol Renal Physiol Source Type: research