scholarly journals The Potential for Renal Injury Elicited by Physical Work in the Heat

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2087 ◽  
Author(s):  
Zachary J. Schlader ◽  
David Hostler ◽  
Mark D. Parker ◽  
Riana R. Pryor ◽  
James W. Lohr ◽  
...  
Keyword(s):  
Blood Flow ◽  
Heat Exposure ◽  
Kidney Injury ◽  
Atp Depletion ◽  
Physical Work ◽  
Sodium Reabsorption ◽  
Renal Tubular Cells ◽  
Intrarenal Blood Flow ◽  
Renal Tubular ◽  
Hot Environments

An epidemic of chronic kidney disease (CKD) is occurring in laborers who undertake physical work in hot conditions. Rodent data indicate that heat exposure causes kidney injury, and when this injury is regularly repeated it can elicit CKD. Studies in humans demonstrate that a single bout of exercise in the heat increases biomarkers of acute kidney injury (AKI). Elevations in AKI biomarkers in this context likely reflect an increased susceptibility of the kidneys to AKI. Data largely derived from animal models indicate that the mechanism(s) by which exercise in the heat may increase the risk of AKI is multifactorial. For instance, heat-related reductions in renal blood flow may provoke heterogenous intrarenal blood flow. This can promote localized ischemia, hypoxemia and ATP depletion in renal tubular cells, which could be exacerbated by increased sodium reabsorption. Heightened fructokinase pathway activity likely exacerbates ATP depletion occurring secondary to intrarenal fructose production and hyperuricemia. Collectively, these responses can promote inflammation and oxidative stress, thereby increasing the risk of AKI. Equivalent mechanistic evidence in humans is lacking. Such an understanding could inform the development of countermeasures to safeguard the renal health of laborers who regularly engage in physical work in hot environments.

scholarly journals HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular cells

2017 ◽  
Vol 313 (4) ◽  
pp. F906-F913 ◽  
Author(s):  
Wei Zhang ◽  
Xiangjun Zhou ◽  
Qisheng Yao ◽  
Yutao Liu ◽  
Hao Zhang ◽  
...  
Keyword(s):  
Cell Injury ◽  
Hypoxia Inducible Factor ◽  
Atp Depletion ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Dependent Manner ◽  
Protective Effects ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

Exosomes are nano-sized vesicles produced and secreted by cells to mediate intercellular communication. The production and function of exosomes in kidney tissues and cells remain largely unclear. Hypoxia is a common pathophysiological condition in kidneys. This study was designed to characterize exosome production during hypoxia of rat renal proximal tubular cells (RPTCs), investigate the regulation by hypoxia-inducible factor-1 (HIF-1), and determine the effect of the exosomes on ATP-depletion-induced tubular cell injury. Hypoxia did not change the average sizes of exosomes secreted by RPTCs, but it significantly increased exosome production in a time-dependent manner. HIF-1 induction with dimethyloxalylglycine also promoted exosome secretion, whereas pharmacological and genetic suppression of HIF-1 abrogated the increase of exosome secretion under hypoxia. The exosomes from hypoxic RPTCs had inhibitory effects on apoptosis of RPTCs following ATP depletion. The protective effects were lost in the exosomes from HIF-1α knockdown cells. It is concluded that hypoxia stimulates exosome production and secretion in renal tubular cells. The exosomes from hypoxic cells are protective against renal tubular cell injury. HIF-1 mediates exosome production during hypoxia and contributes to the cytoprotective effect of the exosomes.

Urinary TCP1-eta: A Cortical Damage Marker for the Pathophysiological Diagnosis and Prognosis of Acute Kidney Injury

2019 ◽  
Vol 174 (1) ◽  
pp. 3-15 ◽  
Author(s):  
Sandra M Sancho-Martínez ◽  
Fernando Sánchez-Juanes ◽  
Víctor Blanco-Gozalo ◽  
Miguel Fontecha-Barriuso ◽  
Laura Prieto-García ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Cortical Damage ◽  
Renal Tubular Cells ◽  
Tubular Necrosis ◽  
Diagnosis And Prognosis ◽  
A Cell ◽  
Renal Tubular ◽  
Dextran Solution

Abstract Acute kidney injury (AKI) is a serious syndrome with increasing incidence and health consequences, and high mortality rate among critically ill patients. Acute kidney injury lacks a unified definition, has ambiguous semantic boundaries, and relies on defective diagnosis. This, in part, is due to the absence of biomarkers substratifying AKI patients into pathophysiological categories based on which prognosis can be assigned and clinical treatment differentiated. For instance, AKI involving acute tubular necrosis (ATN) is expected to have a worse prognosis than prerenal, purely hemodynamic AKI. However, no biomarker has been unambiguously associated with tubular cell death or is able to provide etiological distinction. We used a cell-based system to identify TCP1-eta in the culture medium as a noninvasive marker of damaged renal tubular cells. In rat models of AKI, TCP1-eta was increased in the urine co-relating with renal cortical tubule damage. When kidneys from ATN rats were perfused in situ with Krebs-dextran solution, a portion of the urinary TCP1-eta protein content excreted into urine disappeared, and another portion remained within the urine. These results indicated that TCP1-eta was secreted by tubule cells and was not fully reabsorbed by the damaged tubules, both effects contributing to the increased urinary excretion. Urinary TCP1-eta is found in many etiologically heterogeneous AKI patients, and is statistically higher in patients partially recovered from severe AKI. In conclusion, urinary TCP1-eta poses a potential, substratifying biomarker of renal cortical damage associated with bad prognosis.

scholarly journals Fibrinogen β–derived Bβ15-42 peptide protects against kidney ischemia/ reperfusion injury

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1934-1942 ◽  
Author(s):  
Aparna Krishnamoorthy ◽  
Amrendra Kumar Ajay ◽  
Dana Hoffmann ◽  
Tae-Min Kim ◽  
Victoria Ramirez ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
High Sensitivity ◽  
Kidney Damage ◽  
Therapeutic Interventions ◽  
Mrna Levels ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Injury And Repair

AbstractIschemia/reperfusion (I/R) injury in the kidney is a major cause of acute kidney injury (AKI) in humans and is associated with significantly high mortality. To identify genes that modulate kidney injury and repair, we conducted genome-wide expression analysis in the rat kidneys after I/R and found that the mRNA levels of fibrinogen (Fg)α, Fgβ, and Fgγ chains significantly increase in the kidney and remain elevated throughout the regeneration process. Cellular characterization of Fgα and Fgγ chain immunoreactive proteins shows a predominant expression in renal tubular cells and the localization of immunoreactive Fgβ chain protein is primarily in the renal interstitium in healthy and regenerating kidney. We also show that urinary excretion of Fg is massively increased after kidney damage and is capable of distinguishing human patients with acute or chronic kidney injury (n = 25) from healthy volunteers (n = 25) with high sensitivity and specificity (area under the receiver operating characteristic of 0.98). Furthermore, we demonstrate that Fgβ-derived Bβ15-42 peptide administration protects mice from I/R-induced kidney injury by aiding in epithelial cell proliferation and tissue repair. Given that kidney regeneration is a major determinant of outcome for patients with kidney damage, these results provide new opportunities for the use of Fg in diagnosis, prevention, and therapeutic interventions in kidney disease.

scholarly journals Indirect effects of severe acute respiratory syndrome coronavirus 2 on the kidney in coronavirus disease patients

2020 ◽  
Vol 13 (3) ◽  
pp. 347-353 ◽  
Author(s):  
Aymeric Couturier ◽  
Sophie Ferlicot ◽  
Kévin Chevalier ◽  
Matthieu Guillet ◽  
Marie Essig ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Renal Tubular Cells ◽  
Collapsing Glomerulopathy ◽  
Tubulointerstitial Lesions ◽  
Polymerase Chain ◽  
Renal Tubular ◽  
Novel Coronavirus ◽  
Kidney Lesions

Abstract Among patients hospitalized for novel coronavirus disease (COVID-19), between 10 and 14% develop an acute kidney injury and around half display marked proteinuria and haematuria. Post-mortem analyses of COVID-19 kidney tissue suggest that renal tubular cells and podocytes are affected. Here we report two cases of collapsing glomerulopathy and tubulointerstitial lesions in living COVID-19 patients. Despite our use of sensitive reverse transcription polymerase chain reaction techniques in this study, we failed to detect the virus in blood, urine and kidney tissues. Our observations suggest that these kidney lesions are probably not due to direct infection of the kidney by severe acute respiratory syndrome coronavirus 2.

scholarly journals Small Heat Shock Protein Beta-1 (HSPB1) Is Upregulated and Regulates Autophagy and Apoptosis of Renal Tubular Cells in Acute Kidney Injury

PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0126229 ◽  
Author(s):  
Tatsuki Matsumoto ◽  
Madoka Urushido ◽  
Haruna Ide ◽  
Masayuki Ishihara ◽  
Kazu Hamada-Ode ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Kidney Injury ◽  
Small Heat Shock Protein ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

scholarly journals Exenatide Attenuates Obesity-Induced Mitochondrial Dysfunction by Activating SIRT1 in Renal Tubular Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Yao Wang ◽  
Wei He ◽  
Wei Wei ◽  
Xiaoxue Mei ◽  
Ming Yang ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Kidney Injury ◽  
Protective Effects ◽  
Mitochondrial Apoptosis ◽  
Renal Tubular Cells ◽  
Mitochondrial Ros ◽  
Glucagon Like Peptide 1 ◽  
Treatment Of Obesity ◽  
Underlying Mechanisms ◽  
Renal Tubular

Saturated free fatty acid (FFA)-induced lipotoxicity plays an important role in obesity-induced kidney injury. Exenatide, a Glucagon-like peptide-1 receptor agonist(GLP-1RA), protects against high-fat diet (HFD)-induced kidney injury. The precise mechanism needs to be further explored. This study investigated whether exenatide protects against FFA-induced tubular epithelial cells (TECs) lipotoxicity and elucidated its underlying mechanisms. Here, we show that exenatide treatment reversed HFD induced TECs injuries, including TECs apoptosis and SIRT1 downregulation. The efficacy of exenatide was better than simvastatin. In palmitate (PA)-stimulated HK2 cells, exenatide treatment reversed the downregulation of SIRT1 and prevented an increase in reactive oxygen species (ROS) production, a decrease in mitochondrial membrane potential, and mitochondrial apoptosis. The renal-protective effects of exenatide on the generation of mitochondrial ROS and mitochondrial apoptosis were blocked by inhibiting SIRT1 activation. Collectively, these findings show that exenatide was superior to simvastatin in the treatment of obesity-TECs injuries, the mechanism is partially through SIRT1 restoration, which directly reverses mitochondrial dysfunction and apoptosis.

scholarly journals PTEN alleviates maladaptive repair of renal tubular epithelial cells by restoring CHMP2A-mediated phagosome closure

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Huizhen Wang ◽  
Yifan Wang ◽  
Xin Wang ◽  
Huimi Huang ◽  
Jingfu Bao ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Renal Fibrosis ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Mass Spectrometry Analysis ◽  
Acute Injury ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

AbstractPhosphatase and Tensin Homolog on chromosome Ten (PTEN) has emerged as a key protein that governs the response to kidney injury. Notably, renal adaptive repair is important for preventing acute kidney injury (AKI) to chronic kidney disease (CKD) transition. To test the role of PTEN in renal repair after acute injury, we constructed a mouse model that overexpresses PTEN in renal proximal tubular cells (RPTC) by crossing PTENfl-stop-fl mice with Ggt1-Cre mice. Mass spectrometry-based proteomics was performed after subjecting these mice to ischemia/reperfusion (I/R). We found that PTEN was downregulated in renal tubular cells in mice and cultured HK-2 cells subjected to renal maladaptive repair induced by I/R. Renal expression of PTEN negatively correlated with NGAL and fibrotic markers. RPTC-specific PTEN overexpression relieved I/R-induced maladaptive repair, as indicated by alleviative tubular cell damage, apoptosis, and subsequent renal fibrosis. Mass spectrometry analysis revealed that differentially expressed proteins in RPTC-specific PTEN overexpression mice subjected to I/R were significantly enriched in phagosome, PI3K/Akt, and HIF-1 signaling pathway and found significant upregulation of CHMP2A, an autophagy-related protein. PTEN deficiency downregulated CHMP2A and inhibited phagosome closure and autolysosome formation, which aggravated cell injury and apoptosis after I/R. PTEN overexpression had the opposite effect. Notably, the beneficial effect of PTEN overexpression on autophagy flux and cell damage was abolished when CHMP2A was silenced. Collectively, our study suggests that PTEN relieved renal maladaptive repair in terms of cell damage, apoptosis, and renal fibrosis by upregulating CHMP2A-mediated phagosome closure, suggesting that PTEN/CHMP2A may serve as a novel therapeutic target for the AKI to CKD transition.

scholarly journals The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity

2019 ◽  
Vol 20 (20) ◽  
pp. 5238 ◽  
Author(s):  
Daniela Maria Tanase ◽  
Evelina Maria Gosav ◽  
Smaranda Radu ◽  
Claudia Florida Costea ◽  
Manuela Ciocoiu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
In Vivo Studies ◽  
Renal Tubular Cells ◽  
Renal Tubular ◽  
Induced Apoptosis ◽  
Kidney Injury Molecule 1

Acute kidney injury (AKI) following platinum-based chemotherapeutics is a frequently reported serious side-effect. However, there are no approved biomarkers that can properly identify proximal tubular injury while routine assessments such as serum creatinine lack sensitivity. Kidney-injury-molecule 1 (KIM-1) is showing promise in identifying cisplatin-induced renal injury both in vitro and in vivo studies. In this review, we focus on describing the mechanisms of renal tubular cells cisplatin-induced apoptosis, the associated inflammatory response and oxidative stress and the role of KIM-1 as a possible biomarker used to predict cisplatin associated AKI.

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