scholarly journals Epigenetic Modification Drives Acute Kidney Injury-to-Chronic Kidney Disease Progression

Nephron ◽  
2021 ◽  
pp. 1-11
Author(s):  
Zhenzhen Li ◽  
Ningning Li
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Structural Damage ◽  
Epigenetic Modification ◽  
Kidney Injury ◽  
Epigenetic Modifications ◽  
High Morbidity ◽  
Inflammatory Factor

Acute kidney injury (AKI) is a common clinical critical disease. Due to its high morbidity, increasing risk of complications, high mortality rate, and high medical costs, it has become a global concern for human health problems. Initially, researchers believed that kidneys have a strong ability to regenerate and repair, but studies over the past 20 years have found that kidneys damaged by AKI are often incomplete or even unable to repair. Even when serum creatinine returns to baseline levels, renal structural damage persists for a long time, leading to the development of chronic kidney disease (CKD). The mechanism of AKI-to-CKD transition has not been fully elucidated. As an important regulator of gene expression, epigenetic modifications, such as histone modification, DNA methylation, and noncoding RNAs, may play an important role in this process. Alterations in epigenetic modification are induced by hypoxia, thus promoting the expression of inflammatory factor-related genes and collagen secretion. This review elaborated the role of epigenetic modifications in AKI-to-CKD progression, the diagnostic value of epigenetic modifications biomarkers in AKI chronic outcome, and the potential role of targeting epigenetic modifications in the prevention and treatment of AKI to CKD, in order to provide ideas for the subsequent establishment of targeted therapeutic strategies to prevent the progression of renal tubular-interstitial fibrosis.

scholarly journals Role of SIK1 in the transition of acute kidney injury into chronic kidney disease

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jinxiu Hu ◽  
Jiao Qiao ◽  
Qun Yu ◽  
Bing Liu ◽  
Junhui Zhen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Transcription Factor ◽  
Kidney Disease ◽  
Kidney Injury ◽  
High Morbidity ◽  
Mesenchymal Transition ◽  
Immunohistochemistry Staining ◽  
Hk2 Cells

Abstract Background Acute kidney injury (AKI), with a high morbidity and mortality, is recognized as a risk factor for chronic kidney disease (CKD). AKI-CKD transition has been regarded as one of the most pressing unmet needs in renal diseases. Recently, studies have showed that salt inducible kinase 1 (SIK1) plays a role in epithelial-mesenchymal transition (EMT) and inflammation, which are the hallmarks of AKI-CKD transition. However, whether SIK1 is involved in AKI-CKD transition and by what mechanism it regulates AKI-CKD transition remains unknown. Methods We firstly detected the expression of SIK1 in kidney tissues of AKI patients and AKI mice by immunohistochemistry staining, and then we established Aristolochic acid (AA)-induced AKI-CKD transition model in C57BL/6 mice and HK2 cells. Subsequently, we performed immunohistochemistry staining, ELISA, real-time PCR, Western blot, immunofluorescence staining and Transwell assay to explore the role and underlying mechanism of SIK1 on AKI-CKD transition. Results The expression of SIK1 was down-regulated in AKI patients, AKI mice, AA-induced AKI-CKD transition mice, and HK2 cells. Functional analysis revealed that overexpression of SIK1 alleviated AA-induced AKI-CKD transition and HK2 cells injury in vivo and in vitro. Mechanistically, we demonstrated that SIK1 mediated AA-induced AKI-CKD transition by regulating WNT/β-catenin signaling, the canonical pathway involved in EMT, inflammation and renal fibrosis. In addition, we discovered that inhibition of WNT/β-catenin pathway and its downstream transcription factor Twist1 ameliorated HK2 cells injury, delaying the progression of AKI-CKD transition. Conclusions Our study demonstrated, for the first time, a protective role of SIK1 in AKI-CKD transition by regulating WNT/β-catenin signaling pathway and its downstream transcription factor Twist1, which will provide novel insights into the prevention and treatment AKI-CKD transition in the future.

scholarly journals Role of Parathyroid Hormone Assay and Bedside Ultrasound in the Emergency Department in Differentiating Acute Kidney Injury from Chronic Kidney Disease: A Systematic Review

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Deepali Junnarkar Roy ◽  
Shrikant Digambarrao Pande ◽  
Zhong Hong Liew ◽  
Debajyoti Roy
Keyword(s):  
Systematic Review ◽  
Chronic Kidney Disease ◽  
Emergency Department ◽  
Acute Kidney Injury ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Kidney Injury ◽  
Bedside Ultrasound ◽  
Ipth Level

Introduction. It is not uncommon for patients without preceding history of kidney disease to present to the Emergency department with renal failure. The absence of prior medical records or renal imaging presents a diagnostic challenge. Elevated parathyroid hormone levels or echogenic contracted kidneys on ultrasound are known to point to a diagnosis of chronic kidney disease. The literature in this regard is surprisingly limited. The objective of this study is to assess the role of intact parathyroid (iPTH) blood level and bedside ultrasound in differentiating acute kidney injury from chronic kidney disease. Methods. A systematic review which included a literature search of 3 databases, PubMed, Embase, and Cinahl (R) as also secondary sources, was done. The inclusion criteria evaluated studies which evaluated iPTH or bedside ultrasound in differentiating acute kidney injury from chronic kidney disease. We excluded studies which used other laboratory biomarkers like neutrophil gelatin associated lipocalin (NGAL) or carbamylated haemoglobin. A total of 2256 articles were identified. After screening, the relevant articles were reviewed, and an assessment of their methodological quality was made based on the CASP: Critical Appraisals Skill Programme. Results. Of the 2256 articles identified, after screening, only 5 were identified as relevant. Conclusions. An elevated parathyroid hormone level and echogenic contracted kidneys on bedside ultrasound in the Emergency department can help differentiate acute kidney injury from chronic kidney disease. This differentiation helps decide need for admission as well as further management. Although iPTH level may also rise in acute kidney injury, the value (2.5 times normal) can discriminate it from chronic kidney disease.

scholarly journals Lymphocytes: Versatile Participants in Acute Kidney Injury and Progression to Chronic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Chujin Cao ◽  
Ying Yao ◽  
Rui Zeng
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Injury ◽  
Renal Fibrosis ◽  
Kidney Injury ◽  
Renal Parenchyma ◽  
Health Concern ◽  
High Morbidity ◽  
Parenchyma Cells

Background: Acute kidney injury (AKI) remains a major global public health concern due to its high morbidity and mortality. The progression from AKI to chronic kidney disease (CKD) makes it a scientific problem to be solved. However, it is with lack of effective treatments.Summary: Both innate and adaptive immune systems participate in the inflammatory process during AKI, and excessive or dysregulated immune responses play a pathogenic role in renal fibrosis, which is an important hallmark of CKD. Studies on the pathogenesis of AKI and CKD have clarified that renal injury induces the production of various chemokines by renal parenchyma cells or resident immune cells, which recruits multiple-subtype lymphocytes in circulation. Some infiltrated lymphocytes exacerbate injury by proinflammatory cytokine production, cytotoxicity, and interaction with renal resident cells, which constructs the inflammatory environment and induces further injury, even death of renal parenchyma cells. Others promote tissue repair by producing protective cytokines. In this review, we outline the diversity of these lymphocytes and their mechanisms to regulate the whole pathogenic stages of AKI and CKD; discuss the chronological responses and the plasticity of lymphocytes related to AKI and CKD progression; and introduce the potential therapies targeting lymphocytes of AKI and CKD, including the interventions of chemokines, cytokines, and lymphocyte frequency regulation in vivo, adaptive transfer of ex-expanded lymphocytes, and the treatments of gut microbiota or metabolite regulations based on gut-kidney axis.Key Message: In the process of AKI and CKD, T helper (Th) cells, innate, and innate-like lymphocytes exert mainly pathogenic roles, while double-negative T (DNT) cells and regulatory T cells (Tregs) are confirmed to be protective. Understanding the mechanisms by which lymphocytes mediate renal injury and renal fibrosis is necessary to promote the development of specific therapeutic strategies to protect from AKI and prevent the progression of CKD.

scholarly journals Acute kidney injury pathology and pathophysiology: a retrospective review

2020 ◽  
Author(s):  
Joseph P Gaut ◽  
Helen Liapis
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Biopsy ◽  
Retrospective Review ◽  
Patient Management ◽  
Kidney Injury ◽  
High Morbidity ◽  
Underlying Pathology

Abstract Acute kidney injury (AKI) is the clinical term used for decline or loss of renal function. It is associated with chronic kidney disease (CKD) and high morbidity and mortality. However, not all causes of AKI lead to severe consequences and some are reversible. The underlying pathology can be a guide for treatment and assessment of prognosis. The Kidney Disease: Improving Global Outcomes guidelines recommend that the cause of AKI should be identified if possible. Renal biopsy can distinguish specific AKI entities and assist in patient management. This review aims to show the pathology of AKI, including glomerular and tubular diseases.

scholarly journals Acute kidney injury: a springboard for progression in chronic kidney disease

2010 ◽  
Vol 298 (5) ◽  
pp. F1078-F1094 ◽  
Author(s):  
Manjeri A. Venkatachalam ◽  
Karen A. Griffin ◽  
Rongpei Lan ◽  
Hui Geng ◽  
Pothana Saikumar ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Disease ◽  
Structural Damage ◽  
Kidney Injury ◽  
Tubulointerstitial Fibrosis ◽  
Outcome Analysis ◽  
Renal Disease Progression ◽  
Proximate Cause

Recently published epidemiological and outcome analysis studies have brought to our attention the important role played by acute kidney injury (AKI) in the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). AKI accelerates progression in patients with CKD; conversely, CKD predisposes patients to AKI. This research gives credence to older, well-thought-out wisdom that recovery from AKI is often not complete and is marked by residual structural damage. It also mirrors older experimental observations showing that unilateral nephrectomy, a surrogate for loss of nephrons by disease, compromises structural recovery and worsens tubulointerstitial fibrosis after ischemic AKI. Moreover, review of a substantial body of work on the relationships among reduced renal mass, hypertension, and pathology associated with these conditions suggests that impaired myogenic autoregulation of blood flow in the setting of hypertension, the arteriolosclerosis that results, and associated recurrent ischemic AKI in microscopic foci play important roles in the development of progressively increasing tubulointerstitial fibrosis. How nutrition, an additional factor that profoundly affects renal disease progression, influences these events needs reevaluation in light of information on the effects of calories vs. protein and animal vs. vegetable protein on injury and progression. Considerations based on published and emerging data suggest that a pathology that develops in regenerating tubules after AKI characterized by failure of differentiation and persistently high signaling activity is the proximate cause that drives downstream events in the interstitium: inflammation, capillary rarefaction, and fibroblast proliferation. In light of this information, we advance a comprehensive hypothesis regarding the pathophysiology of AKI as it relates to the progression of kidney disease. We discuss the implications of this pathophysiology for developing efficient therapeutic strategies to delay progression and avert ESRD.

scholarly journals Toll-Like Receptors in Acute Kidney Injury

2021 ◽  
Vol 22 (2) ◽  
pp. 816
Author(s):  
Cristina Vázquez-Carballo ◽  
Melania Guerrero-Hue ◽  
Cristina García-Caballero ◽  
Sandra Rayego-Mateos ◽  
Lucas Opazo-Ríos ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Pathological Condition ◽  
Kidney Injury ◽  
Preclinical Studies ◽  
Toll Like Receptors ◽  
Middle Income ◽  
Increased Risk

Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological condition.

scholarly journals Deprivation and kidney disease—a predictor of poor outcomes

2019 ◽  
Vol 13 (2) ◽  
pp. 128-132
Author(s):  
Greg D Guthrie ◽  
Samira Bell
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Renal Disease ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Confounding Factors ◽  
Growing Body ◽  
Poor Outcomes

Abstract There is a growing body of evidence for the role of deprivation in a broad spectrum of diseases including renal disease. Deprivation has been demonstrated to be associated with poorer outcomes across a range of renal diseases including acute kidney injury (AKI), chronic kidney disease and transplantation. In this issue of Clinical Kidney Journal, Hounkpatin et al. describe the association of socioeconomic deprivation with incidence, mortality and resolution of AKI in a large UK cohort. Investigating deprivation as a factor influencing either incidence or outcome of disease is challenging due to variations in measures of deprivation used and other confounding factors that may be contributing to the observed differences. In this editorial, we review the current literature examining the role of deprivation in renal disease.

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