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sepsis-induced acute kidney injury

Yizi Xia, Ying Chen, Luming Tang, Zheng Wang, Yu Zheng
Acute kidney injury (AKI) is a severe complication of sepsis with a high mortality and morbidity. Pterostilbene (Pte) has been suggested to confer anti-apoptotic and anti-inflammatory effects. In the current study, the effects of Pte on AKI were evaluated in septic mice. Cecal ligation and puncture surgery was performed to induce sepsis. The results suggested that Pte administration significantly decreased the levels of serum urea nitrogen and creatinine, and improved the survival rate of septic mice. Additionally, the renal injury induced by sepsis was attenuated by pterostilbene treatment...
April 2018: Experimental and Therapeutic Medicine
Naif O Al-Harbi, Ahmed Nadeem, Sheikh F Ahmad, Moureq R Alotaibi, Abdullah F AlAsmari, Wael A Alanazi, Mohammad M Al-Harbi, Ahmad M El-Sherbeeny, Khalid E Ibrahim
Sepsis affects millions of people worldwide and is associated with acute kidney injury (AKI). Innate and adaptive immune cells have been shown to play an important role in AKI through release of various inflammatory mediators which include reactive oxidant species (ROS). Acetate, a short chain fatty acid produced by gut bacteria has anti-inflammatory properties and has also been shown to modulate oxidative stress in different immune cells. Effects of acetate have been shown to be both GPR43 dependent and independent in different cells/tissues...
March 12, 2018: International Immunopharmacology
Xiaoyan Wen, Liyan Cui, Seth Morrisroe, Donald Maberry, David R Emlet, Simon C Watkins, Neil A Hukriede, John A Kellum
Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish (Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for sepsis-associated AKI research. We introduced Edwardsiella tarda (E.tarda) to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality...
March 14, 2018: American Journal of Physiology. Renal Physiology
Xinxin Chen, Huan Tong, Yu Chen, Chaosheng Chen, Jingjing Ye, Qingfei Mo, Guangju Zhao, Guangliang Hong, Chenfei Zheng, Zhongqiu Lu
Background: The role of Klotho (KL) in sepsis-induced acute kidney injury (AKI) and the potential relationship between KL and autophagy in septic AKI were investigated. Materials and methods: A murine model of sepsis-induced AKI was established by cecal ligation and puncture (CLP). Mice undergoing CLP and immortalized proximal tubular epithelial human HK-2 cells that were exposed to lipopolysaccharide (LPS) were treated with recombinant KL, autophagy stimulator rapamycin (Rap), and autophagy suppressor 3-methyladenine (3-MA)...
2018: OncoTargets and Therapy
Paolo Calzavacca, Lindsea C Booth, Yugeesh R Lankadeva, Simon R Bailey, Louise M Burrell, Michael Bailey, Rinaldo Bellomo, Clive N May
INTRODUCTION: Supra-clinical doses of clonidine appear beneficial in experimental sepsis, but there is limited understanding of the effects of clonidine at clinically relevant doses. METHODS: In conscious sheep, with implanted renal and pulmonary artery flow probes, sepsis was induced by infusion of live Escherichia coli. At 24 hours, a high clinical dose of clonidine (HCDC) [1.0 μg/kg/h], a low clinical dose of clonidine (LCDC) [0.25 μg/kg/h] or vehicle, was infused for 8 hours...
February 27, 2018: Shock
Salma Mukhtar Mir, Halley Gora Ravuri, Raj Kumar Pradhan, Sairam Narra, Jerald Mahesh Kumar, Madhusudana Kuncha, Sanjit Kanjilal, Ramakrishna Sistla
Sepsis-induced acute kidney injury (AKI) is responsible for 70-80% mortality in intensive care patients due to elevated levels of endotoxin, Lipopolysaccharide (LPS) caused by gram-negative infections. Ferulic acid (FA), a phenolic phytochemical is known for its renal protection on various induced models of nephrotoxicity. However, the curative effect of FA in LPS-induced AKI is not well studied. This study aimed to investigate the effect of FA on LPS-induced AKI in mice model and to understand the protective mechanisms involved, to provide evidence for FA in the treatment of AKI...
February 12, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Junyi Wang, Xinjing Gao, Dong Wang, Zhiyong Wang, Zhibo Li, Dong Liu, Lei Xu
OBJECTIVE: To evaluate the diagnostic value of contrast-enhanced ultrasound in acute kidney injury (AKI) caused by sepsis. METHODS: The sepsis patients admitted to intensive care unit of Tianjin Third Central Hospital from January 2015 to June 2017 were enrolled. All of the patients were completed the 6-hour Bundle treatment and the bilateral renal contrast-enhanced ultrasound within 24 hours, and the peak signal intensity (PSI), peak intensity time (PIT), wash internal rate (WIR) and renal function parameters were measured at the same time...
February 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Luis Toro, Víctor Barrientos, Pablo León, Macarena Rojas, Magdalena Gonzalez, Alvaro González-Ibáñez, Sebastián Illanes, Keigo Sugikawa, Néstor Abarzúa, César Bascuñán, Katherine Arcos, Carlos Fuentealba, Ana María Tong, Alvaro A Elorza, María Eugenia Pinto, Rodrigo Alzamora, Carlos Romero, Luis Michea
It is accepted that osteoblasts/osteocytes are the major source for circulating fibroblast growth factor 23 (FGF23). However, erythropoietic cells of bone marrow also express FGF23. The modulation of FGF23 expression in bone marrow and potential contribution to circulating FGF23 has not been well studied. Moreover, recent studies show that plasma FGF23 may increase early during acute kidney injury (AKI). Erythropoietin, a kidney-derived hormone that targets erythropoietic cells, increases in AKI. Here we tested whether an acute increase of plasma erythropoietin induces FGF23 expression in erythropoietic cells of bone marrow thereby contributing to the increase of circulating FGF23 in AKI...
January 27, 2018: Kidney International
Xiuhua Li, Yusheng Li, Kan Shen, Hongqiang Li, Jianwen Bai
Platelets are traditionally considered to be essential components of primary hemostasis. Recent investigations have revealed that platelets can be activated in patients with sepsis and are implicated in the development of sepsis and sepsis-induced-acute kidney injury (SAKI). In the present study, ticagrelor was used to induce a mouse model of SAKI by cecal ligation and puncture. It was found that ticagrelor could inhibit platelet activity, decrease the levels of interleukin-1β and serum creatinine, reduce infiltration of neutrophils in renal tissue, and attenuate cell apoptosis in the kidney...
January 25, 2018: Platelets
Zuowang Cheng, Ruixia Qi, Liqun Li, Qiang Liu, Wenqian Zhang, Xia Zhou, Dongmei Xu, Thaddeus D Allen, Silin Pan, Ju Liu
Sepsis, the systemic inflammatory responses after infection, remains a serious cause of morbidity and mortality in critically ill patients. The anti-malarial agent dihydroartemisinin (DHA) has been shown to be anti-inflammatory. In this study, we examined the effects of DHA on sepsis-induced acute kidney injury (AKI) and explored the mechanism underlying its mode of action in AKI. In a lipopolysaccharide (LPS)-induced mouse model, we observed that DHA treatment ameliorated glomerular injury, and relieved elevation of the urine albumin to creatinine ratio (UACR) and serum creatinine...
January 17, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Satoshi Sunahara, Eizo Watanabe, Masahiko Hatano, Paul E Swanson, Takehiko Oami, Lisa Fujimura, Youichi Teratake, Takashi Shimazui, Chiwei Lee, Shigeto Oda
The role of autophagy in the maintenance of renal homeostasis during sepsis is not well understood. We therefore aimed to determine the influence of autophagy on kidney during sepsis using a murine sepsis model, i.e. cecal ligation and puncture (CLP). In CLP treated animals, the number of autolysosomes observed by electron microscopy increased over time. The number of autophagosomes in CLP animals decreased relative sham operated controls at 24 hrs after CLP, indicating that autophagy flux is already diminishing by that time...
January 18, 2018: Scientific Reports
Sabiha Sahin, Dilek Burukoglu Donmez
BACKGROUND Acute kidney injury (AKI) secondary to sepsis is a major cause of morbidity and mortality in the human intensive care unit (ICU). Kidney function and the histological findings of AKI were investigated in an experimental rat model with sepsis induced by cecal ligation and puncture (CLP) and compared with and without treatment with carnosine (beta-alanyl-L-histidine). MATERIAL AND METHODS Twenty-four Sprague-Dawley rats were randomly divided into three groups consisting eight rats in each: Group 1 - control; Group 2 - septic shock; and Group 3 - septic shock treated with carnosine...
January 15, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Jun Zhou, Hongtao Chen, Youling Fan
Acute kidney injury (AKI) is a common and serious disease characterized by a rapid decline in renal function and has an unacceptably high mortality rate with no effective treatment beyond supportive care. AKI can be induced by many factors such as ischemia/reperfusion (IR), sepsis, and drug-induced nephrotoxicity. However, the molecular mechanisms of AKI are poorly understood. A non-coding RNA (ncRNA) is a RNA molecule that is not translated into a protein. NcRNAs play multiple roles in cellular processes, and mutations or imbalances of these molecules within the body can cause a variety of diseases...
November 21, 2017: Oncotarget
Fabienne Venet, Guillaume Monneret
Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis can induce acute kidney injury and multiple organ failures and represents the most common cause of death in the intensive care unit. Sepsis initiates a complex immune response that varies over time, with the concomitant occurrence of both pro-inflammatory and anti-inflammatory mechanisms. As a result, most patients with sepsis rapidly display signs of profound immunosuppression, which is associated with deleterious consequences...
February 2018: Nature Reviews. Nephrology
Yan Xu, Yan Jiang, Wentao Gai, Botao Yu
Acute kidney injury (AKI) is a severe complication of sepsis, which largely contributes to the associated high mortality rate. Tenuigenin (TNG) is a natural product isolated from Polygala tenuifolia root, which possesses anti-inflammatory and anti-oxidant properties. The present study investigated the effects of TNG on sepsis-associated AKI in mice subjected to cecal ligation and puncture (CLP). TNG was demonstrated to alleviate sepsis-induced AKI by reducing pathological changes and significantly decreasing the levels of blood urea nitrogen, serum creatinine and kidney coefficient...
November 2017: Experimental and Therapeutic Medicine
Demet Alaygut, Meral Torun Bayram, Belde Kasap, Alper Soylu, Mehmet Türkmen, Salih Kavukcu
AIM: To investigate different etiologies and management of the rhabdomyolysis in children. METHODS: Eight pediatric rhabdomyolysis cases who applied to the Dokuz Eylul University Faculty of Medicine Department of Pediatric Nephrology with different etiologies between January 2004 and January 2012 were evaluated in terms of age, gender, admission symptoms, physical examination findings, factors provoking rhabdomyolysis, number of rhabdomyolysis attacks, laboratory results, family history and the final diagnosis received after the treatment...
November 8, 2017: World Journal of Clinical Pediatrics
Grazia Maria Virzì, Anna Clementi, Alessandra Brocca, Claudio Ronco
Gram-negative sepsis is a major cause of morbidity and mortality in critical ill patients. Recent findings in molecular biology and in signaling pathways have enhanced our understanding of its pathogenesis and opened up opportunities of innovative therapeutic approaches. Endotoxin plays a pivotal role in the pathogenesis of multi-organ dysfunction in the setting of gram-negative sepsis. Indeed, heart and kidney impairments seem to be induced by the release of circulating pro-inflammatory and pro-apoptotic mediators triggered by endotoxin interaction with immune cells...
November 22, 2017: Blood Purification
Qiu Yang, Dongshan Zhang, Ya Li, Yongquan Li, Yinpeng Li
Excessive inflammatory response and apoptosis play an important role in the sepsis-induced liver injury. Paclitaxel, a diterpene alkaloid of Taxus brevifolia, is widely used as an anti-tumor drug and shows protective effects on acute lung and kidney injury. However, whether it has a protective effect against sepsis-induced liver injury has not been reported. The objective of this study was to investigate the protective effects of paclitaxel in septic liver injury in mice and associated molecular mechanisms...
November 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
A T Press, M J Butans, T P Haider, C Weber, S Neugebauer, M Kiehntopf, U S Schubert, M G Clemens, M Bauer, A Kortgen
Simultaneous assessment of excretory liver and kidney function is still an unmet need in experimental stress models as well as in critical care. The aim of the study was to characterize two polymethine-dyes potentially suitable for this purpose in vivo. Plasma disappearance rate and elimination measurements of simultaneously injected fluorescent dyes DY-780 (hepato-biliary elimination) and DY-654(renal elimination) were conducted using catheter techniques and intravital microscopy in animals subjected to different organ injuries, i...
November 13, 2017: Scientific Reports
Jonathan M Street, Erik H Koritzinsky, Tiffany R Bellomo, Xuzhen Hu, Peter S T Yuen, Robert A Star
Sepsis and acute kidney injury (AKI) synergistically increase morbidity and mortality in the ICU. How sepsis reduces GFR and causes AKI is poorly understood; one proposed mechanism includes tubuloglomerular feedback (TGF). When sodium reabsorption by the proximal tubules is reduced in normal animals, the macula densa senses increased luminal sodium chloride, then adenosine 1a receptor (A1aR) signaling triggers tubuloglomerular feedback, reducing GFR through afferent arteriole vasoconstriction. We measured GFR and systemic hemodynamics early during cecal ligation and puncture-induced sepsis in wild-type and A1aR knockout mice...
November 8, 2017: American Journal of Physiology. Renal Physiology
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