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Sepsis induced acute kidney injury

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https://www.readbyqxmd.com/read/28090081/metabolic-reprogramming-and-tolerance-during-sepsis-induced-aki
#1
REVIEW
Hernando Gómez, John A Kellum, Claudio Ronco
The host defence against infection is an adaptive response in which several mechanisms are deployed to decrease the pathogen load, limit tissue injury and restore homeostasis. In the past few years new evidence has suggested that the ability of the immune system to limit the microbial burden - termed resistance - might not be the only defence mechanism. In fact, the capacity of the host to decrease its own susceptibility to inflammation- induced tissue damage - termed tolerance - might be as important as resistance in determining the outcome of the infection...
January 16, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28063928/mir-107-induces-tnf-%C3%AE-secretion-in-endothelial-cells-causing-tubular-cell-injury-in-patients-with-septic-acute-kidney-injury
#2
Shanshan Wang, Zengdi Zhang, Jun Wang, Hongjun Miao
Activation of endothelial cells plays a key role in septic acute kidney injury (AKI). This study investigated the role of miRNA in endothelial-induced tubular cell injury in sepsis. Circulating endothelial cells (CECs) from septic AKI, non-septic AKI, septic non-AKI patients and healthy volunteers were isolated and cultured, and HK2 cells were exposed to CEC-conditioned medium. CEC-conditioned medium prepared from septic AKI patients led to cell shrinkage, decreased E-cadherin, the release of NAG and cell apoptosis in HK2 cells...
January 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28061889/urinary-exosomal-activating-transcriptional-factor-3-as-the-early-diagnostic-biomarker-for-sepsis-induced-acute-kidney-injury
#3
Tanaporn Panich, Wiwat Chancharoenthana, Poorichaya Somparn, Jiraphorn Issara-Amphorn, Nattiya Hirankarn, Asada Leelahavanichkul
BACKGROUND: An early sepsis-induced acute kidney injury (sepsis-AKI) biomarker is currently in needed. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a candidate of sepsis-AKI biomarker but with different cut-point values. Urinary exosomal activating transcriptional factor 3 (uATF3) has been mentioned as an interesting biomarker. METHODS: We conducted experiments in mice and a prospective, multicenter study in patients as a proof of concept that urine exosome is an interesting biomarker...
January 7, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28052874/inhibition-of-hdac6-protects-against-rhabdomyolysis-induced-acute-kidney-injury
#4
Shi Yingfeng, Xu Liuqing, Tang Jinhua, Fang Lu, Ma Shuchen, Ma Xiaoyan, Nie Jing, Pi Xiaoling, Qiu Andong, Zhuang Shougang, Liu Na
Histone deacetylase 6 (HDAC6) inhibition has been reported to protect against ischemic stroke and prolong survival after sepsis in animal models. However, it remains unknown whether HDAC6 inhibition offers a renoprotective effect after acute kidney injury (AKI). In this study, we examined the therapeutic effect of tubastatin A (TA), a highly selective inhibitor of HDAC6, on AKI in a murine model of glycerol (GL) injection-induced rhabdomyolysis. Following GL injection, the mice developed severe acute tubular injury as indicated by renal dysfunction, expression of neutrophil gelatinase-associated lipocalin (NGAL), an injury marker of renal tubules and increase of TUNEL positive tubular cells...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28029146/protective-effects-of-luteolin-on-lipopolysaccharide-induced-acute-renal-injury-in-mice
#5
Shao-Bin Xin, Hao Yan, Jing Ma, Qiang Sun, Li Shen
BACKGROUND Sepsis can cause serious acute kidney injury in bacterium-infected patients, especially in intensive care patients. Luteolin, a bioactive flavonoid, has renal protection and anti-inflammatory effects. This study aimed to investigate the effect and underlying mechanism of luteolin in attenuating lipopolysaccharide (LPS)-induced renal injury. MATERIAL AND METHODS ICR mice were treated with LPS (25 mg/kg) with or without luteolin pre-treatment (40 mg/kg for three days). The renal function, histological changes, degree of oxidative stress, and tubular apoptosis in these mice were examined...
December 28, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28012971/effects-of-a-human-recombinant-alkaline-phosphatase-during-impaired-mitochondrial-function-in-human-renal-proximal-tubule-epithelial-cells
#6
Esther Peters, Tom Schirris, Alexander H van Asbeck, Jelle Gerretsen, Jennifer Eymael, Angel Ashikov, Merel J W Adjobo-Hermans, Frans Russel, Peter Pickkers, Rosalinde Masereeuw
Sepsis-associated acute kidney injury is a multifactorial syndrome in which inflammation and renal microcirculatory dysfunction play a profound role. Subsequently, renal tubule mitochondria reprioritize cellular functions to prevent further damage. Here, we investigated the putative protective effects of human recombinant alkaline phosphatase (recAP) during inhibition of mitochondrial respiration in conditionally immortalized human proximal tubule epithelial cells (ciPTEC). Full inhibition of mitochondrial oxygen consumption was obtained after 24h antimycin A treatment, which did not affect cell viability...
December 22, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27993148/blood-transfusion-improves-renal-oxygenation-and-renal-function-in-sepsis-induced-acute-kidney-injury-in-rats
#7
Lara Zafrani, Bulent Ergin, Aysegul Kapucu, Can Ince
BACKGROUND: The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. METHODS: Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7)...
December 20, 2016: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/27918369/preadministration-of-hydrogen-rich-water-protects-against-lipopolysaccharide-induced-sepsis-and-attenuates-liver-injury
#8
Masumi Iketani, Jumi Ohshiro, Takuya Urushibara, Mayumi Takahashi, Tomio Arai, Hideo Kawaguchi, Ikuroh Ohsawa
Despite significant advances in antibiotic therapy and intensive care, sepsis remains the most common cause of death in intensive care units. We previously reported that molecular hydrogen (H2) acts as a therapeutic and preventive antioxidant. Here, we show that preadministration of H2-dissolved water (HW) suppresses lipopolysaccharide (LPS)-induced endotoxin shock in mice. Drinking HW for 3 days before LPS injection prolonged survival in a mouse model of sepsis. The H2 concentration immediately increased in the liver but not in the kidney after drinking HW...
December 1, 2016: Shock
https://www.readbyqxmd.com/read/27902475/osthole-protects-sepsis-induced-acute-kidney-injury-via-down-regulating-nf-%C3%AE%C2%BAb-signal-pathway
#9
Chen Yu, Peng Li, Dong Qi, Lei Wang, Hong-Lin Qu, Yue-Juan Zhang, Xue-Kai Wang, Hua-Ying Fan
BACKGROUND AND PURPOSE: As a natural coumarin derivative from the Cnidium monnieri(L)Cusson fruit, osthole consists of 7-methoxy-8-isopentenoxy-coumarin. The purpose of this research is to study the mechanism and effect of osthole on sepsis-induced acute kidney injury. EXPERIMENTAL APPROACH: The protective effect of osthole on mouse macrophage RAW 264.7 and HK-2 cells induced by LPS in vitro and on acute kidney injury model induced by sepsis and established by puncture and cecal ligation (CLP) in vivo were tested...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27813491/hyperin-protects-against-lps-induced-acute-kidney-injury-by-inhibiting-tlr4-and-nlrp3-signaling-pathways
#10
Gong Chunzhi, Li Zunfeng, Qin Chengwei, Bu Xiangmei, Yu Jingui
Hyperin is a flavonoid compound derived from Ericaceae, Guttifera, and Celastraceae that has been shown to have various biological effects, such as anti-inflammatory and anti-oxidant effects. However, there is no evidence to show the protective effects of hyperin on lipopolysaccharide (LPS)-induced acute kidney injury (AKI). Therefore, we investigated the protective effects and mechanism of hyperin on LPS-induced AKI in mice. The levels of TNF-α, IL-6, and IL-1β were tested by ELISA. The effects of hyperin on blood urea nitrogen (BUN) and serum creatinine were also detected...
November 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27767365/early-septic-insult-in-neonatal-pigs-increases-serum-and-urinary-soluble-fas-ligand-and-decreases-kidney-function-without-inducing-significant-renal-apoptosis
#11
Hitesh Soni, Adebowale Adebiyi
Apoptosis of renal tubular and glomerular cells during kidney disease involves activation of Fas ligand (FasL)-dependent death pathway. The significance of FasL in neonates with septic acute kidney injury (AKI) is unresolved, but an increase in renal FasL production, and/or infiltration of circulating FasL into the kidneys may occur following initial septic insult. Here, we examined whether soluble Fas ligand (sFasL) levels are altered during early phase of septic AKI in neonates. Six hours of polymicrobial sepsis elicited by cecal ligation and puncture (CLP) elevated serum C-reactive protein (CRP) (a bacteremia and sepsis marker) concentration in anesthetized and mechanically ventilated neonatal pigs...
October 21, 2016: Renal Failure
https://www.readbyqxmd.com/read/27760529/the-effect-of-continuous-venovenous-hemofiltration-on-neutrophil-gelatinase-associated-lipocalin-plasma-levels-in-patients-with-septic-acute-kidney-injury
#12
Xingui Dai, Tao Li, Zhenhua Zeng, Chunlai Fu, Shengbiao Wang, Yeping Cai, Zhongqing Chen
BACKGROUND: It is known that continuous venonenous hemofiltration (CVVH) does not affect the plasma level of neutrophil gelatinase-associated lipocalin (pNGAL) in acute kidney injury (AKI) patients. However, because of the unique pathophysiology underlying AKI caused by sepsis, the effect of CVVH on pNGAL in this clinical setting is less certain. The purpose of this study was to determine the effect of CVVH on pNGAL in sepsis-induced AKI patients. METHODS: Between August 1, 2014, and December 31, 2014, 42 patients with sepsis-induced AKI underwent CVVH in the general intensive care unit of our institution and were consecutively enrolled in this study...
October 19, 2016: BMC Nephrology
https://www.readbyqxmd.com/read/27760303/effects-of-a-human-recombinant-alkaline-phosphatase-on-renal-hemodynamics-oxygenation-and-inflammation-in-two-models-of-acute-kidney-injury
#13
Esther Peters, Bülent Ergin, Asli Kandil, Ebru Gurel-Gurevin, Andrea van Elsas, Rosalinde Masereeuw, Peter Pickkers, Can Ince
Two small clinical trials indicated that administration of bovine intestinal alkaline phosphatase (AP) improves renal function in critically ill patients with sepsis-associated acute kidney injury (AKI), for which the mechanism of action is not completely understood. Here, we investigated the effects of a newly developed human recombinant AP (recAP) on renal oxygenation and hemodynamics and prevention of kidney damage and inflammation in two in vivo AKI models. To induce AKI, male Wistar rats (n=18) were subjected to renal ischemia (30min) and reperfusion (I/R), or sham-operated...
December 15, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27754216/os-32-01-atrial-natriuretic-peptide-improves-urine-flow-at-proximal-tubules-in-septic-acute-kidney-injury
#14
Hiroaki Kitamura, Daisuke Nakano, Zhang Yifan, Akira Nishiyama
OBJECTIVE: Carperitide, alpha-human atrial natriuretic peptide, is used in expectation of protecting the kidney during sepsis in internal care unit; however, the detailed mechanism of action has not been clarified yet. As septic acute kidney injury (AKI) does not induce characteristic histological damage, we aimed assess the effects of carperitide treatment on the decline of renal function during lipopolysaccharide-induced AKI by using real-time intravital imaging technique. DESIGN AND METHOD: The renal function was analyzed by the bolus-shot FITC-inulin kinetics method that visualizes the tubular flow after free filtration from glomeruli...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27671340/effects-of-n-acetylcysteine-nac-supplementation-in-resuscitation-fluids-on-renal-microcirculatory-oxygenation-inflammation-and-function-in-a-rat-model-of-endotoxemia
#15
Bulent Ergin, Philippe Guerci, Lara Zafrani, Frank Nocken, Asli Kandil, Ebru Gurel-Gurevin, Cihan Demirci-Tansel, Can Ince
BACKGROUND: Modulation of inflammation and oxidative stress appears to limit sepsis-induced damage in experimental models. The kidney is one of the most sensitive organs to injury during septic shock. In this study, we evaluated the effect of N-acetylcysteine (NAC) administration in conjunction with fluid resuscitation on renal oxygenation and function. We hypothesized that reducing inflammation would improve the microcirculatory oxygenation in the kidney and limit the onset of acute kidney injury (AKI)...
December 2016: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/27661757/sepsis-induced-acute-kidney-injury
#16
Hernando Gómez, John A Kellum
PURPOSE OF REVIEW: Sepsis is a common and frequently fatal condition in which mortality has been consistently linked to increasing organ dysfunction. For example, acute kidney injury (AKI) occurs in 40-50% of septic patients and increases mortality six to eight-fold. However, the mechanisms by which sepsis causes organ dysfunction are not well understood and hence current therapy remains reactive and nonspecific. RECENT FINDINGS: Recent studies have challenged the previous notion that organ dysfunction is solely secondary to hypoperfusion, by showing, for example, that AKI occurs in the setting of normal or increased renal blood flow; and that it is characterized not by acute tubular necrosis or apoptosis, but rather by heterogeneous areas of colocalized sluggish peritubular blood flow and tubular epithelial cell oxidative stress...
December 2016: Current Opinion in Critical Care
https://www.readbyqxmd.com/read/27643176/os-32-01-atrial-natriuretic-peptide-improves-urine-flow-at-proximal-tubules-in-septic-acute-kidney-injury
#17
Hiroaki Kitamura, Daisuke Nakano, Zhang Yifan, Akira Nishiyama
OBJECTIVE: Carperitide, alpha-human atrial natriuretic peptide, is used in expectation of protecting the kidney during sepsis in internal care unit; however, the detailed mechanism of action has not been clarified yet. As septic acute kidney injury (AKI) does not induce characteristic histological damage, we aimed assess the effects of carperitide treatment on the decline of renal function during lipopolysaccharide-induced AKI by using real-time intravital imaging technique. DESIGN AND METHOD: The renal function was analyzed by the bolus-shot FITC-inulin kinetics method that visualizes the tubular flow after free filtration from glomeruli...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27620507/protective-effects-of-sirtuin-3-in-a-murine-model-of-sepsis-induced-acute-kidney-injury
#18
Wen-Yu Zhao, Lei Zhang, Ming-Xing Sui, You-Hua Zhu, Li Zeng
Acute kidney injury (AKI) is a rapid loss of kidney function characterized by damage to renal tubular cells driven by mitochondrial dysregulation and oxidative stress. Here, we used a murine caecal ligation and puncture (CLP) model of sepsis-induced AKI to study the role of sirtuin 3 (SIRT3), a NAD(+) dependent deacetylase critical for the maintenance of mitochondrial viability, in AKI-related renal tubular cell damage and explored the underlying mechanisms. CLP induced alterations in kidney function and morphology were associated with SIRT3 downregulation, and SIRT3 deletion exacerbated CLP-induced kidney dysfunction, renal tubular cell injury and apoptosis, mitochondrial alterations, and ROS production in a knockout mouse model...
September 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27613897/protective-effect-of-nicotine-on-sepsis-induced-oxidative-multi-organ-damage-role-of-neutrophils
#19
Zarife Nigâr Özdemir-Kumral, Dilek Özbeyli, Ahmet Faruk Özdemir, M Buğra Karaaslan, Kübra Kaytaz, Mustafa F Kara, Olgu Enis Tok, Feriha Ercan, Berrak Ç Yeğen
INTRODUCTION: Despite its adverse health consequences, tobacco smoking is associated with lower incidence of several neurodegenerative and inflammatory diseases. The present study is aimed to show the effects of nicotine, major tobacco constituent, on five organs targeted by sepsis. METHODS: Male Wistar albino rats received tap water with (5 mg/kg) or without nicotine for 14 days. Under ketamine anesthesia, sepsis (n=50) was induced by ligation and punction of the cecum, while sham group (n=8) had only laparotomy...
August 3, 2016: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
https://www.readbyqxmd.com/read/27602552/physiological-aspects-of-toll-like-receptor-4-activation-in-sepsis-induced-acute-kidney-injury
#20
REVIEW
S B Anderberg, T Luther, R Frithiof
Sepsis-induced acute kidney injury (SI-AKI) is common and associated with high mortality. Survivors are at increased risk of chronic kidney disease. The precise mechanism underlying SI-AKI is unknown, and no curative treatment exists. Toll-like receptor 4 (TLR4) activates the innate immune system in response to exogenous microbial products. The result is an inflammatory reaction aimed at clearing a potential infection. However, the consequence may also be organ dysfunction as the immune response can cause collateral damage to host tissue...
September 7, 2016: Acta Physiologica
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