scholarly journals Effects of Exercise on Acute Kidney Injury Biomarkers and the Potential Influence of Fluid Intake

2021 ◽  
pp. 1-7
Author(s):  
Loris Allan Juett ◽  
Lewis J. James ◽  
Stephen Andrew Mears
Keyword(s):  
Acute Kidney Injury ◽  
Muscle Damage ◽  
Fluid Intake ◽  
Kidney Injury ◽  
Strenuous Exercise ◽  
Physical Work ◽  
Tubular Injury ◽  
Potential Influence ◽  
Water Ingestion ◽  
Renal Tubular

Acute kidney injury (AKI) incidence (diagnosed by changes in serum creatinine [Cr]) following prolonged endurance events has been reported to be anywhere from 4 to 85%, and hypohydration may contribute to this. Whilst an increase in serum Cr indicates impaired kidney function, this might be influenced by muscle damage. Therefore, the use of other AKI biomarkers which can detect renal tubular injury may be more appropriate. The long-term consequences of AKI are not well understood, but there are some potential concerns of an increased subsequent risk of chronic kidney disease (CKD). Therefore, this brief review explores the effects of exercise training/competition on novel AKI biomarkers and the potential influence of fluid intake. The increase in novel AKI biomarkers following prolonged endurance events suggests renal tubular injury. This is likely due to the long duration and relatively high exercise intensity, producing increased sympathetic tone, body temperature, hypohydration, and muscle damage. Whilst muscle damage appears to be an important factor in the pathophysiology of exercise-associated AKI, it may require coexisting hypohydration. Fluid intake seems to play a role in exercise-associated AKI, as maintaining euhydration with water ingestion during simulated physical work in the heat appears to attenuate rises in AKI biomarkers. The composition of fluid intake may also be important, as high-fructose drinks have been shown to exacerbate AKI biomarkers. However, it is yet to be seen if these findings are applicable to athletes performing strenuous exercise in a temperate environment. Additionally, further work should examine the effects of repeated bouts of strenuous exercise on novel AKI biomarkers.

scholarly journals Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model

2019 ◽  
Vol 317 (2) ◽  
pp. F264-F274 ◽  
Author(s):  
Satoshi Tanimura ◽  
Katsuyuki Tanabe ◽  
Hiromasa Miyake ◽  
Kana Masuda ◽  
Keigo Tsushida ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Endothelial Cells ◽  
Kidney Injury ◽  
Protective Effects ◽  
Tubular Injury ◽  
Injury Model ◽  
Peritubular Capillaries ◽  
Renal Tubular ◽  
And Function ◽  
Hospital Acquired

Acute kidney injury (AKI) is frequently encountered in clinical practice, particularly secondarily to cardiovascular surgery and administration of nephrotoxic agents, and is increasingly recognized for initiating a transition to chronic kidney disease. Clarifying the pathogenesis of AKI could facilitate the development of novel preventive strategies, because the occurrence of hospital-acquired AKI is often anticipated. Vasohibin-1 (VASH1) was initially identified as an antiangiogenic factor derived from endothelial cells. VASH1 expression in endothelial cells has subsequently been reported to enhance cellular stress tolerance. Considering the importance of maintaining peritubular capillaries in preventing the progression of AKI, the present study aimed to examine whether VASH1 deletion is involved in the pathogenesis of cisplatin-induced AKI. For this, we injected male C57BL/6J wild-type (WT) and VASH1 heterozygous knockout (VASH1+/−) mice intraperitoneally with either 20 mg/kg cisplatin or vehicle solution. Seventy-two hours after cisplatin injection, increased serum creatinine concentrations and renal tubular injury accompanied by apoptosis and oxidative stress were more prominent in VASH1+/− mice than in WT mice. Cisplatin-induced peritubular capillary loss was also accelerated by VASH1 deficiency. Moreover, the increased expression of ICAM-1 in the peritubular capillaries of cisplatin-treated VASH1+/− mice was associated with a more marked infiltration of macrophages into the kidney. Taken together, VASH1 expression could have protective effects on cisplatin-induced AKI probably by maintaining the number and function of peritubular capillaries.

scholarly journals Inhibition of Mitochondrial Complex I Aggravates Folic Acid-Induced Acute Kidney Injury

2019 ◽  
Vol 44 (5) ◽  
pp. 1002-1013 ◽  
Author(s):  
Wen Zhang ◽  
Yunwen Yang ◽  
Huiping Gao ◽  
Yue Zhang ◽  
Zhanjun Jia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Folic Acid ◽  
Mitochondrial Dysfunction ◽  
Complex I ◽  
Kidney Injury ◽  
Mitochondrial Complex I ◽  
Tubular Injury ◽  
Mitochondrial Complex ◽  
Renal Tubular

Background: Some researches revealed that mitochondrial dysfunction is associated with various kidney injury. However, the role of mitochondrial dysfunction in the pathogenesis of acute kidney injury (AKI) still needs evidence. Methods: We evaluated the effect of mitochondrial complex I inhibitor rotenone on folic acid (FA)-induced AKI in mice. Results: Strikingly, the mice pretreated with rotenone at a dose of 200 ppm in food showed exacerbated kidney injury as shown by higher levels of blood urea nitrogen and creatinine compared with FA alone group. Meanwhile, both renal tubular injury score and the expression of renal tubular injury marker neutrophil gelatinase-associated lipocalin were further elevated in rotenone-pretreated mice, suggesting the deteriorated renal tubular injury. Moreover, the decrements of mitochondrial DNA copy number and the expressions of mitochondrial Cytochrome c oxidase subunit 1, mitochondrial NADH dehydrogenase subunit 1, and mitochondria-specific superoxide dismutase (SOD2) in the kidneys of FA-treated mice were further reduced in rotenone-pretreated mice, indicating the aggravated mitochondrial damage. In parallel with the SOD2 reduction, the oxidative stress markers of malondialdehyde and HO-1 displayed greater increment in AKI mice with rotenone pretreatment in line with the deteriorated apoptotic response and inflammation. Conclusion: Our results suggested that the inhibition of mitochondrial complex I activity aggravated renal tubular injury, mitochondrial damage, oxidative stress, cell apoptosis, and inflammation in FA-induced AKI.

scholarly journals Lack of significant renal tubular injury despite acute kidney injury in acute decompensated heart failure

2012 ◽  
Vol 14 (6) ◽  
pp. 597-604 ◽  
Author(s):  
Matthias Dupont ◽  
Kevin Shrestha ◽  
Dhssraj Singh ◽  
Adiveh Awad ◽  
Cynthia Kovach ◽  
...  
Keyword(s):  
Heart Failure ◽  
Acute Kidney Injury ◽  
Acute Decompensated Heart Failure ◽  
Kidney Injury ◽  
Decompensated Heart Failure ◽  
Tubular Injury ◽  
Renal Tubular

scholarly journals Isoliquiritigenin attenuates LPS-induced acute kidney injury through suppression of HMGB1 pathway in renal tubular against ferritinophagy

2020 ◽  
Author(s):  
Yun Tang ◽  
Yanmei Wang ◽  
Chan Wang ◽  
Meidie Yu ◽  
Li Li ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Dysfunction ◽  
Kidney Injury ◽  
Tubular Injury ◽  
Renal Tubular Cells ◽  
Septic Acute Kidney Injury ◽  
Life Threatening ◽  
Renal Tubular

Abstract Septic acute kidney injury (AKI) mainly results in life-threatening renal dysfunction involving renal tubular injury to bring heavy burden to patients in intensive care unit (ICU). However, there is still a lack of therapy to prevent septic AKI effectively and inexpensive. To observe the role and novel mechanism of isoliquiritigenin (ISL) which isolated from the roots of licorice in septic AKI, we used LPS to induce renal tubular injury upon septic AKI both in vitro and in vivo. 50mg/kg ISL and 5 mg/kg Ferrostatin-1 were once given to the male C57BL/6 mice one hour before 1 mg/kg LPS i.p injection. 50 μM and 100 μM ISL respectively pre-treat the human renal tubular cells 5 hrs before 2 μg/ml LPS stimulation. We found ISL pretreatment apparently reversed LPS-induced renal dysfunction and ameliorated murine renal tubular injury by suppression HMGB1 pathway. Furthermore, we observed that LPS induced autophagy and ferroptosis in renal tubular, whereas ISL pretreatment significantly suppress autophagy and ferroptosis of renal tubular both in vitro and in vivo. Mechanically, autophagy activated ferroptosis via NCOA4-mediated ferritinophagy. Moreover, HMGB1 is required for ferritinophagy in renal tubular. ISL treatment inhibited the expression of HMGB1. Taken together, these results suggest that ISL protects LPS-induced acute kidney injury through suppression of HMGB1 pathway in renal tubular against ferritinophagy.

scholarly journals Impact of Ciprofloxacin With Autophagy on Acute Kidney Injury

2021 ◽  
Author(s):  
Woo Yeong Park ◽  
Sun-Ha Lim ◽  
Yaerim Kim ◽  
Jin Hyuk Paek ◽  
Kyubok Jin ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Caspase 3 ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
Beclin 1 ◽  
Control Group ◽  
Renal Tubules ◽  
Tubular Injury ◽  
Renal Tubular Cells ◽  
Renal Tubular

Abstract Renal tubular injury caused by oxidative stress and inflammation results in acute kidney injury. Recent research reported that antibiotics may restore deteriorated renal tubules, but the underlying mechanism remains unclear. Therefore, we investigated the efficacy and mechanism of action of antibiotics against renal tubular injury. We screened ciprofloxacin, ceftizoxime, minocycline, and netilmicin and selected ciprofloxacin to examine further because of its low toxicity towards renal tubular cells. We evaluated the effect of ciprofloxacin on cell survival by analyzing apoptosis and autophagy. TUNEL assay results showed that the ciprofloxacin group had less apoptotic cells than the control group. The ratio of cleaved caspase 3 to caspase 3, the final effector in the apoptosis process, was decreased, but the ratio of Bax to Bcl-2 located upstream of caspase 3 was not decreased in the ciprofloxacin group. Therefore, apoptosis inhibition does not occur via Bax/Bcl-2. Conversely, the levels of phosphorylated Bcl-2, and Beclin-1, an autophagy marker, were increased, and that of caspase-3 was decreased in the ciprofloxacin group. This indicates that ciprofloxacin enhanced autophagy, increasing the amount of free Beclin-1 via phosphorylated Bcl-2, and inhibited caspase activity. Therefore, ciprofloxacin might increase renal cell viability through the autophagy activation in acute kidney injury.

Abstract P544: Osteopontin Deficiency Decreases Autophagy and Exacerbates Tubular Injury in Acute Kidney Injury Induced by Folic Acid

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Tomoaki Nagao ◽  
Takafumi Okura ◽  
Akiko Tanino ◽  
Ken-ichi Miyoshi ◽  
Masayoshi Kukida ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Folic Acid ◽  
Kidney Injury ◽  
Immunohistochemical Analysis ◽  
Tubular Injury ◽  
Histological Changes ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

Osteopontin (OPN), a secreted glycosylated phosphoprotein and pro-inflammatory cytokine, has been implicated in the pathology of several renal conditions, especially renal fibrosis in chronic kidney disease. OPN is slightly expressed in renal tubular cells in normal condition, but after acute tubular injury, OPN is highly induced in these cells. However, the role of induced OPN is still unclear. The aim of this study was to clarify the roles of OPN in acute kidney injury (AKI). AKI was induced in wild type (WT) and OPN knockout (KO) mice by using folic acid (FA) injection (0.35mg/kg). After 2days of injection, 34% of WT mice died, whereas 54% of KO died from renal failure. Kidneys from survived mice were removed and the renal histological changes, protein expression were examined. BUN and Creatinine levels were markedly elevated in WT-AKI and KO-AKI mice (BUN: WT-sham; 25.7±4.7mg/dl, WT-AKI; 315.0±173.2mg/dl, KO-AKI; 337.7±163.7mg/dl, Creatinine: WT-sham; 0.08±0.03 mg/dl, WT-AKI; 1.60±0.87 mg/dl, KO-AKI; 1.80±0.94 mg/dl). Renal OPN mRNA expression was increased in WT-AKI mice compared to WT-sham mice (p<0.05). High levels of OPN expression in renal tubular cells were induced in WT-AKI mice. TUNEL positive tubular cells were increased in KO-AKI mice compared to WT-AKI mice. In immunohistochemical analysis, Kidney injury molecules 1 (Kim-1) positive tubular cells were also highly increased in KO-AKI mice compared to WT-AKI mice. In contrast, LC3B (autophagy related protein) positive tubular cells were decreased in KO-AKI mice compared to WT-AKI mice. These results indicate that OPN deficiency exacerbates tubular injury via through the inhibiting autophagy in folic acid induced AKI mice.

Renal tubular injury as an uncommon presentation of Wilson’s disease

2021 ◽  
Vol 2 (3) ◽  
Author(s):  
Hadar Mudrik-Zohar ◽  
◽  
Keren Cohen-Hagai ◽  
Danny Alon ◽  
◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Wilson’S Disease ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
Wilson's Disease ◽  
Tubular Dysfunction ◽  
Tubular Injury ◽  
Uncommon Presentation ◽  
Renal Tubular

Wilson's disease is an autosomal recessive disorder caused by a mutant ATP7B gene on chromosome 13. This mutation causes a reduction in hepatic copper excretion, which accumulates in hepatocytes and deposits in other tissues and organs (brain, cornea, kidney, etc.) as the disease progresses. Wilson's disease was described worldwide, with estimated prevalence of one case per 30,000 live births. Age of presentation is usually 4-60 years; however, the disease may present at any age. Clinical manifestations are predominantly hepatic, neurologic and psychiatric. Renal involvement is less common and characterized by proximal tubular dysfunction, Glomerular Filtration Rate (GFR) decline, renal tubular acidosis, aminoaciduria and nephrolithiasis. Herein, we aimed to report a case which describes an uncommon path to the diagnosis of this rare, yet well-known disease. The diagnosis resulted from an investigation of acute kidney injury in a 48-year-old man. Keywords: Wilson’s disease; Acute kidney injury; Renal tubular injury.

scholarly journals Rhabdomyolysis-Induced AKI Was Ameliorated in NLRP3 KO Mice via Alleviation of Mitochondrial Lipid Peroxidation in Renal Tubular Cells

2020 ◽  
Vol 21 (22) ◽  
pp. 8564
Author(s):  
Seok Jong Song ◽  
Su-mi Kim ◽  
Sang-ho Lee ◽  
Ju-Young Moon ◽  
Hyeon Seok Hwang ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Acute Kidney Injury ◽  
Cell Viability ◽  
Kidney Injury ◽  
Critical Factor ◽  
Tubular Injury ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Glycerol Injection ◽  
Renal Tubular

Introduction: A recent study showed that early renal tubular injury is ameliorated in Nod-like receptor pyrin domain-containing protein 3 (NLRP3) KO mice with rhabdomyolysis-induced acute kidney injury (RIAKI). However, the precise mechanism has not been determined. Therefore, we investigated the role of NLRP3 in renal tubular cells in RIAKI. Methods: Glycerol-mediated RIAKI was induced in NLRP3 KO and wild-type (WT) mice. The mice were euthanized 24 h after glycerol injection, and both kidneys and plasma were collected. HKC-8 cells were treated with ferrous myoglobin to mimic a rhabdomyolytic environment. Results: Glycerol injection led to increase serum creatinine, aspartate aminotransferase (AST), and renal kidney injury molecule-1 (KIM-1) level; renal tubular necrosis; and apoptosis. Renal injury was attenuated in NLRP3 KO mice, while muscle damage and renal neutrophil recruitment did not differ between NLRP3 KO mice and WT mice. Following glycerin injection, increases in cleaved caspase-3, poly (ADP-ribose) polymerase (PARP), and a decrease in the glutathione peroxidase 4 (GPX-4) level were observed in the kidneys of mice with RIAKI, and these changes were alleviated in the kidneys of NLRP3 KO mice. NLRP3 was upregulated, and cell viability was suppressed in HKC-8 cells treated with ferrous myoglobin. Myoglobin-induced apoptosis and lipid peroxidation were significantly decreased in siNLRP3-treated HKC-8 cells compared to ferrous myoglobin-treated HKC-8 cells. Myoglobin reduced the mitochondrial membrane potential and increased mitochondrial fission and reactive oxygen species (ROS) and lipid peroxidation levels, which were restored to normal levels in NLRP3-depleted HKC-8 cells. Conclusions: NLRP3 depletion ameliorated renal tubular injury in a murine glycerol-induced acute kidney injury (AKI) model. A lack of NLRP3 improved tubular cell viability via attenuation of myoglobin-induced mitochondrial injury and lipid peroxidation, which might be the critical factor in protecting the kidney.

A novel STING antagonist H151 ameliorates cisplatin-induced acute kidney injury and mitochondrial dysfunction

2021 ◽  
Author(s):  
Wei Gong ◽  
Lingling Lu ◽  
Yu Zhou ◽  
Jiaye Liu ◽  
Haoyang Ma ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Mitochondrial Morphology ◽  
Tubular Injury ◽  
Mitochondrial Injury ◽  
Genes Expression ◽  
Platinum Based Chemotherapy ◽  
Kidney Morphology ◽  
Renal Tubular

Stimulator of interferon genes (STING) is an important adaptor in the cytosolic DNA sensing pathways. Recent study found that the deletion of STING ameliorated cisplatin-induced acute kidney injury (AKI), suggesting that STING could serve as a potential target for AKI therapy. Up to now, a series of small-molecule STING inhibitors/antagonists have been identified. However, none of research was performed to explore the role of human STING inhibitors in AKI. Here we investigated the effect of a newly generated covalent antagonist H151 targeting both human and murine STING, in cisplatin-induced AKI. We found that H151 treatment significantly ameliorated cisplatin-induced kidney injury as shown by the improvement of renal function, kidney morphology and renal inflammation. Besides, tubular cell apoptosis and the increased renal tubular injury marker NGAL induced by cisplatin were also effectively attenuated in H151-treated mice. Moreover, the mitochondrial injury caused by cisplatin was also reversed as evidenced by the improved mitochondrial morphology, restored mitochondrial DNA (mtDNA) content, and reversed mitochondrial genes expression. Finally, we observed enhanced mtDNA levels in the plasma of patients receiving platinum-based chemotherapy compared to the healthy controls, which could potentially activate STING signaling. Taken together, these findings suggested that H151 could be a potential therapeutic agent for treating AKI possibly through inhibiting STING-mediated inflammation and mitochondrial injury.

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