scholarly journals A regulatory miRNA–mRNA network is associated with transplantation response in acute kidney injury

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Duan Guo ◽  
Yu Fan ◽  
Ji-Rong Yue ◽  
Tao Lin

Abstract Background Acute kidney injury (AKI) is a life-threatening complication characterized by rapid decline in renal function, which frequently occurs after transplantation surgery. However, the molecular mechanism underlying the development of post-transplant (post-Tx) AKI still remains unknown. An increasing number of studies have demonstrated that certain microRNAs (miRNAs) exert crucial functions in AKI. The present study sought to elucidate the molecular mechanisms in post-Tx AKI by constructing a regulatory miRNA–mRNA network. Results Based on two datasets (GSE53771 and GSE53769), three key modules, which contained 55 mRNAs, 76 mRNAs, and 151 miRNAs, were identified by performing weighted gene co-expression network analysis (WGCNA). The miRDIP v4.1 was applied to predict the interactions of key module mRNAs and miRNAs, and the miRNA–mRNA pairs with confidence of more than 0.2 were selected to construct a regulatory miRNA–mRNA network by Cytoscape. The miRNA–mRNA network consisted of 82 nodes (48 mRNAs and 34 miRNAs) and 125 edges. Two miRNAs (miR-203a-3p and miR-205-5p) and ERBB4 with higher node degrees compared with other nodes might play a central role in post-Tx AKI. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that this network was mainly involved in kidney-/renal-related functions and PI3K–Akt/HIF-1/Ras/MAPK signaling pathways. Conclusion We constructed a regulatory miRNA–mRNA network to provide novel insights into post-Tx AKI development, which might help discover new biomarkers or therapeutic drugs for enhancing the ability for early prediction and intervention and decreasing mortality rate of AKI after transplantation.

2021 ◽  
Vol 12 ◽  
Author(s):  
Xue Li ◽  
Yu Zou ◽  
Yuan-Yuan Fu ◽  
Jia Xing ◽  
Kai-Yue Wang ◽  
...  

Folic acid (FA)-induced renal tubule damage, which is characterized by extensive inflammation, is a common model of acute kidney injury (AKI). Pyroptosis, a pro-inflammatory form of cell death due to the activation of inflammatory caspases, is involved in AKI progression. Ibudilast, a TLR4 antagonist, has been used in the clinic to exert an anti-inflammatory effect on asthma. However, researchers have not explored whether ibudilast exerts a protective effect on AKI by inhibiting inflammation. In the present study, ibudilast reversed FA-induced AKI in mice, as indicated by the reduced serum creatinine and urea nitrogen levels, and improved renal pathology, as well as the downregulation of kidney injury marker-1. In addition, ibudilast significantly increased the production of the anti-inflammatory factor IL-10 while suppressing the secretion of the pro-inflammatory cytokine TNF-α and macrophage infiltration. Moreover, in the injured kidney, ibudilast reduced the levels of both inflammasome markers (NLRP3) and pyroptosis-related proteins (caspase-1, IL1-β, IL-18, and GSDMD cleavage), and decreased the number of TUNEL-positive cells. Further mechanistic studies showed that ibudilast administration inhibited the FA-induced upregulation of TLR4, blocked NF-κB nuclear translocation, and reduced the phosphorylation of NF-κB and IκBα, p38, ERK, and JNK. Thus, this study substantiates the protective effect of ibudilast on FA-induced AKI in mice and suggests that protection might be achieved by reducing pyroptosis and inflammation, likely through the inhibition of TLR4-mediated NF-κB and MAPK signaling pathways.


Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 338 ◽  
Author(s):  
Ying Wang ◽  
Juan Cai ◽  
Chengyuan Tang ◽  
Zheng Dong

Acute kidney injury (AKI) is a major kidney disease characterized by rapid decline of renal function. Besides its acute consequence of high mortality, AKI has recently been recognized as an independent risk factor for chronic kidney disease (CKD). Maladaptive or incomplete repair of renal tubules after severe or episodic AKI leads to renal fibrosis and, eventually, CKD. Recent studies highlight a key role of mitochondrial pathology in AKI development and abnormal kidney repair after AKI. As such, timely elimination of damaged mitochondria in renal tubular cells represents an important quality control mechanism for cell homeostasis and survival during kidney injury and repair. Mitophagy is a selective form of autophagy that selectively removes redundant or damaged mitochondria. Here, we summarize our recent understanding on the molecular mechanisms of mitophagy, discuss the role of mitophagy in AKI development and kidney repair after AKI, and present future research directions and therapeutic potential.


Vascular ◽  
2021 ◽  
pp. 170853812110125
Author(s):  
Altuğ Ösken ◽  
Ahmet Öz ◽  
Muhammed Keskin ◽  
Evliya Akdeniz ◽  
Hasan Şahan ◽  
...  

Objectives Contrast-induced acute kidney injury (CI-AKI) is a life-threatening complication that leads to comorbidities and prolonged hospital stay lengths in the setting of peripheral interventions. The presence of some CI-AKI risk factors has already been investigated. In this study, we evaluated the predictors of CI-AKI after carotid artery stenting. Methods A total of 389 patients with 50% to 99% carotid artery stenosis who underwent carotid artery stenting were included in this study. Patients were grouped according to CI-AKI status. Results CI-AKI developed in 26 (6.6%) patients. Age, baseline creatinine level, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were higher and estimated glomerular filtration rate, haemoglobin and lymphocyte count were lower in CI-AKI patients. In the multivariate regression analysis, the neutrophil-to-lymphocyte ratio triggered a 1.39- to 2.63-fold increase in the risk of CI-AKI onset ( p < 0.001). Conclusions The neutrophil-to-lymphocyte ratio may be a significant predictor of CI-AKI in patients with carotid artery stenting and higher neutrophil-to-lymphocyte ratio values may be independently associated with CI-AKI.


2015 ◽  
Vol 8 (5) ◽  
pp. 120 ◽  
Author(s):  
Syed Raza Shah ◽  
Sameer Altaf Tunio ◽  
Mohammad Hussham Arshad ◽  
Zorays Moazzam ◽  
Komal Noorani ◽  
...  

<p>Acute renal failure is defined as a rapid decrease in the glomerular filtration rate, occurring over a period of hours to days and by the inability of the kidney to regulate fluid and electrolyte homeostasis appropriately. AKI is a catastrophic, life-threatening event in critically ill patients. AKI can be divided into pre-renal injury, intrinsic kidney disease (including vascular insults) and obstructive uropathies. The prognosis of AKI is highly dependent on the underlying cause of the injury. Children who have AKI as a component of multisystem failure have a much higher mortality rate than children with intrinsic renal disease. Treatment of AKI is subjected to risk stratification and ongoing damage control measures, such as patients with sepsis, exposure to nephrotoxic agents, ischemia, bloody diarrhea, or volume loss, could be helped by optimizing the fluid administrations, antibiotics possessing least nephrotoxic potential, blood transfusion where hemoglobin is dangerously low, limiting the use of nephrotoxic agents including radio contrast use, while maximize the nutrition. Acute kidney injury remains a complex disorder with an apparent differentiation in pathology between septic and nonseptic forms of the disease. Although more studies are still required, progress in this area has been steady over the last decade with purposeful international collaboration.</p>


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Abdulmuttalip Simsek ◽  
Volkan Tugcu ◽  
Ali Ihsan Tasci

Acute kidney injury (AKI) is a common and strong problem in the diagnosis of which based on measurement of BUN and serum creatinine. These traditional methods are not sensitive and specific for the diagnosis of AKI. AKI is associated with increased morbidity and mortality in critically ill patients and a quick detection is impossible with BUN and serum creatinine. A number of serum and urinary proteins have been identified that may messenger AKI prior to a rise in BUN and serum creatinine. New biomarkers of AKI, including NGAL, KIM-1, cystatin-C, IL-18, and L-FABP, are more favourable tests than creatinine which have been identified and studied in several experimental and clinical training. This paper will discuss some of these new biomarkers and their potential as useful signs of AKI. We searched the literature using PubMed and MEDLINE with acute kidney injury, urine, and serum new biomarkers and the articles were selected only from publication types in English.


2020 ◽  
Vol 58 (228) ◽  
Author(s):  
Pukar Thapa ◽  
Sudhamshu KC ◽  
Achyut Bikram Hamal ◽  
Dilip Sharma ◽  
Sandip Khadka ◽  
...  

Introduction: Acute kidney injury is a common and life-threatening event in patients with liver cirrhosis occurring in approximately 20-50% of hospitalized patients of liver cirrhosis. Pre-renal acute kidney injury, the hepatorenal syndrome type of acute kidney injury and acute tubular necrosis represent the common causes. The aim of this study was to study the profile of acute kidney injury in patients with liver cirrhosis. Methods: Consecutive patients of liver cirrhosis admitted in Liver unit of Bir Hospital were studied to see the presence of acute kidney injury in this hospital based descriptive cross-sectional study. Clinical and laboratory parameters along with various clinical outcome were compared between different groups categorized by the severity of liver disease and renal dysfunction. Results: Out of 302 liver cirrhosis patients, 56 (18.5%) had acute kidney injury among which 23 (46%) were found to have pre-renal acute kidney injury, 15 (30%) with hepatorenal syndrome– acute kidney injury and 12 (24%) with intrinsic renal disease. Patients with higher stages of acute kidney injury had longer duration of hospital stay and hepatorenal syndrome-acute kidney injury was seen in patients with higher grade of ascites and with hyponatremia. Conclusions: Acute kidney injury is a common occurrence in patients with advanced liver cirrhosis with pre-renal acute kidney injury being the commonest cause. Median hospital stay is directly affected by the severity of acute kidney injury and hepatorenal syndrome–acute kidney injury was seen in patients with higher grade of ascites and hyponatremia. Early identification of patients at high risk for acute kidney injury may help to reduce mortality and contain costs.  


Nephron ◽  
2021 ◽  
pp. 1-7
Author(s):  
Marlies Ostermann ◽  
Emma Karsten ◽  
Nuttha Lumlertgul

New biomarkers for acute kidney injury (AKI) have improved our understanding of the etiology and pathogenesis of AKI. Depending on their origin, function, and kinetic profile, biomarkers have a role in screening, diagnosis, prognostication, and monitoring of AKI. This offers opportunities to improve the management of AKI, but concerns and limitations remain. In this review, we summarize the current role of new AKI biomarkers in the management of AKI and outline some of the ongoing limitations and challenges.


2021 ◽  
Vol 5 (1) ◽  
pp. 6-13
Author(s):  
Charles E. Middleton IV ◽  
William Daley ◽  
Neha Varshney

The clinical features of corona virus disease 2019 (COVID-19) are variable, but the majority of patients experience mild flu-like symptoms. The cases of severe disease include complications such as progressive pneumonia, acute kidney injury, multi-organ failure, and even death. This paper explores the association between COVID-19 and its effect on multiple organ systems and how the subsequent treatment of this disease can itself lead to morbidity and mortality. We present a case which emphasizes the life threatening gastrointestinal complications associated with treatment of acute kidney injury (AKI) in a patient with COVID-19. We conclude that the patients whose treatment regimens utilize medical resins should be closely monitored for gastrointestinal complications so as to mitigate the known adverse effects associated with these drugs, such as colonic mucosal ulceration, perforation, or even death.


2021 ◽  
Vol 8 (2) ◽  
pp. 300
Author(s):  
Medo M. Kuotsu ◽  
N. Biplab Singh ◽  
Nyamnyei Konyak ◽  
Vikie-o Khruomo ◽  
Senjele Kath ◽  
...  

N, N’-dimethyl-4, 4’-bipyridinium dichloride (paraquat) is a herbicide commonly used in India that leads to fatal outcome on ingestion. Paraquat interferes in the intracellular electron transfer systems inhibiting the reduction of NADP to NADPH resulting in accumulation of superoxide radical causing lipid cell membranes destruction leading to various organ damage. Life threatening effects such as acute kidney injury as paraquat elimination is mainly by kidney, acute respiratory distress syndrome and multi-organ failure are the causes of mortality in paraquat poisoning. There is no specific antidotes for paraquat poisoning so prevention and aggressive decontamination remains the mainstay of management in case of exposure or ingestion. Paraquat poisoning presentation may vary in cases depending on the amount of paraquat consumed and thus the outcome. Here we report a case of a 17 years old male who presented with acute kidney injury following ingestion of paraquat in a suicidal attempt. In our case, induced vomiting of the stomach content readily after ingestion of the poison, early haemodialysis, use of immunosuppression such as methylprednisolone, cyclophosphamide and antioxidants such as acetylcysteine, Vitamin C and Vitamin E as free radical scavenging agent , supportive measures such as adequate hydration and antibiotics might have helped in the patient’s survival. The case fatality remains very high in paraquat poisoning till date owing to lack of effective treatment options.


Sign in / Sign up

Export Citation Format

Share Document