scholarly journals The Key Role of Epithelial to Mesenchymal Transition (EMT) in Hypertensive Kidney Disease

2019 ◽  
Vol 20 (14) ◽  
pp. 3567 ◽  
Author(s):  
Teresa Seccia ◽  
Brasilina Caroccia ◽  
Maria Piazza ◽  
Gian Paolo Rossi

Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT), originally described as a key process for organ development and metastasis budding in cancer, plays a key role in the development of renal fibrosis in several diseases, including hypertensive nephroangiosclerosis. We herein reviewed the concept of EMT and its role in renal diseases, with particular focus on hypertensive kidney disease, the second leading cause of end-stage renal disease after diabetes mellitus. After discussing the pathophysiology of hypertensive nephropathy, the ‘classic’ view of hypertensive nephrosclerosis entailing hyalinization, and sclerosis of interlobular and afferent arterioles, we examined the changes occurring in the glomerulus and tubulo-interstitium and the studies that investigated the role of EMT and its molecular mechanisms in hypertensive kidney disease. Finally, we examined the reasons why some studies failed to provide solid evidence for renal EMT in hypertension.

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jantina A. Manning ◽  
Sonia S. Shah ◽  
Andrej Nikolic ◽  
Tanya L. Henshall ◽  
Yeesim Khew-Goodall ◽  
...  

AbstractKidney disease progression can be affected by Na+ abundance. A key regulator of Na+ homeostasis is the ubiquitin ligase NEDD4-2 and its deficiency leads to increased Na+ transport activity and salt-sensitive progressive kidney damage. However, the mechanisms responsible for high Na+ induced damage remain poorly understood. Here we show that a high Na+ diet compromised kidney function in Nedd4-2-deficient mice, indicative of progression toward end-stage renal disease. Injury was characterized by enhanced tubule dilation and extracellular matrix accumulation, together with sustained activation of both Wnt/β-catenin and TGF-β signaling. Nedd4-2 knockout in cortical collecting duct cells also activated these pathways and led to epithelial–mesenchymal transition. Furthermore, low dietary Na+ rescued kidney disease in Nedd4-2-deficient mice and silenced Wnt/β-catenin and TGF-β signaling. Our study reveals the important role of NEDD4-2-dependent ubiquitination in Na+ homeostasis and protecting against aberrant Wnt/β-catenin/TGF-β signaling in progressive kidney disease.


2016 ◽  
Vol 21 (4) ◽  
pp. 344-352 ◽  
Author(s):  
Yusuke Sata ◽  
Markus P. Schlaich

Sympathetic activation is a hallmark of chronic and end-stage renal disease and adversely affects cardiovascular prognosis. Hypertension is present in the vast majority of these patients and plays a key role in the progressive deterioration of renal function and the high rate of cardiovascular events in this patient cohort. Augmentation of renin release, tubular sodium reabsorption, and renal vascular resistance are direct consequences of efferent renal sympathetic nerve stimulation and the major components of neural regulation of renal function. Renal afferent nerve activity directly influences sympathetic outflow to the kidneys and other highly innervated organs involved in blood pressure control via hypothalamic integration. Renal denervation of the kidney has been shown to reduce blood pressure in many experimental models of hypertension. Targeting the renal nerves directly may therefore be specifically useful in patients with chronic and end-stage renal disease. In this review, we will discuss the potential role of catheter-based renal denervation in patients with impaired kidney function and also reflect on the potential impact on other cardiovascular conditions commonly associated with chronic kidney disease such as heart failure and arrhythmias.


PEDIATRICS ◽  
1983 ◽  
Vol 72 (6) ◽  
pp. 840-846
Author(s):  
Alan M. Krensky ◽  
Joseph M. Reddish ◽  
Rita Littlewood Teele

Review of 2,700 abdominal ultrasonic examinations revealed 56 patients whose kidneys showed increased echogenicity. Echogenic kidneys were associated with medical renal disease in 94% of cases (30% glomerular, 48% tubulointerstitial, 16% end-stage) and with no detectable renal disease in 6% (three patients). Patterns of increased echogenicity and renal size were evaluated. Specific patterns occurred in end-stage renal disease and polycystic kidney disease. Other medical renal diseases had overlapping ultrasonographic features. Some generalizations could be made although increased echogenicity was often nonspecific.


2021 ◽  
pp. 353-382
Author(s):  
Gopesh K. Modi ◽  
Vivekanand Jha

Assessing renal function, Urinalysis, Proteinuria, Hematuria, Chyluria, Imaging in renal disease, Kidney biopsy, Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), Diabetic Nephropathy, End Stage Renal Disease and Dialysis, Kidney Transplantation, Glomerular diseases, Acute glomerulonephritis, Urinary schistosomiasis (bilharzia), Infections and Kidney Disease, Rapidly Progressive glomerulonephritis, Tubulointerstitial Disease, Urinary Tract Infection, Vesico-ureteric reflux, Renal Stones, Renal Disease in Pregnancy, Renal Artery Stenosis, Renal Mass, Inherited Renal Diseases


2018 ◽  
Vol 13 (5) ◽  
pp. 659-668 ◽  
Author(s):  
Sara Lovisa ◽  
Giannicola Genovese ◽  
Silvio Danese

Abstract Intestinal fibrosis is an inevitable complication in patients with inflammatory bowel disease [IBD], occurring in its two major clinical manifestations: ulcerative colitis and Crohn’s disease. Fibrosis represents the final outcome of the host reaction to persistent inflammation, which triggers a prolonged wound healing response resulting in the excessive deposition of extracellular matrix, eventually leading to intestinal dysfunction. The process of epithelial-to-mesenchymal transition [EMT] represents an embryonic program relaunched during wound healing, fibrosis and cancer. Here we discuss the initial observations and the most recent findings highlighting the role of EMT in IBD-associated intestinal fibrosis and fistulae formation. In addition, we briefly review knowledge on the cognate process of endothelial-to-mesenchymal transition [EndMT]. Understanding EMT functionality and the molecular mechanisms underlying the activation of this mesenchymal programme will permit designing new therapeutic strategies to halt the fibrogenic response in the intestine.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shulin Li ◽  
Fei Wang ◽  
Dong Sun

AbstractChronic kidney disease (CKD) affects 8–16% of the population worldwide and is characterized by fibrotic processes. Understanding the cellular and molecular mechanisms underpinning renal fibrosis is critical to the development of new therapeutics. Microvascular injury is considered an important contributor to renal progressive diseases. Vascular endothelium plays a significant role in responding to physical and chemical signals by generating factors that help maintain normal vascular tone, inhibit leukocyte adhesion and platelet aggregation, and suppress smooth muscle cell proliferation. Loss of the rich capillary network results in endothelial dysfunction, hypoxia, and inflammatory and oxidative effects and further leads to the imbalance of pro- and antiangiogenic factors, endothelial cell apoptosis and endothelial-mesenchymal transition. New techniques, including both invasive and noninvasive techniques, offer multiple methods to observe and monitor renal microcirculation and guide targeted therapeutic strategies. A better understanding of the role of endothelium in CKD will help in the development of effective interventions for renal microcirculation improvement. This review focuses on the role of microvascular injury in CKD, the methods to detect microvessels and the novel treatments to ameliorate renal fibrosis.


KYAMC Journal ◽  
2013 ◽  
Vol 2 (2) ◽  
pp. 182-186
Author(s):  
ST Ahmed ◽  
MA Rahim ◽  
Z Ali ◽  
MM Iqbal

Background: Chronic Kidney Disease (CKD) is the third most common non-communicable disease throughout the world. Studies have shown that kidney patients suffer much from hypertension, diabetes than glomerulonephritis. Many of these CKD patients ultimately terminate to End Stage Renal Disease (ESRD) when life is not sustainable unless hemodialysis is initiated. Aim: The aim of this study was to identify primary renal disease leading to ESRD requiring hemodialysis and associated co-morbidities. Material and methods: Data was collected purposively from selected six hemodialysis centers. Patients were selected purposively who were available at the time of interview. Data was collected on working days at three shifts After taking informed consent from patients the pre-tested questionnaire was filled up by taking general history, family history, socioeconomic condition, drug history and available records were reviewed for collecting previous biochemical parameters. All entered data were analyzed by using SPSS program version 13.0. Result: Among total 393 subjects, male was 247(63%) and female 146 (37%). Majority were middle aged. Glomerulonephritis were found to be the leading cause of End Stage Renal Disease (ESRD) (50.4%), followed by diabetes in 31.1%, Poly Cystic Kidney Disease (PKD) 5.3%, Renal Stone in 3.7% and rest other. Among the study population hypertension was the most common co morbidity disease (63%) followed by ischemic heart disease and Cerebrovascular accidents. Conclusion: Glomerulonephritis was found to be the leading cause of End Stage Renal Disease (ESRD) and diabetic nephropathy was the second common cause. Hypertension was the most common associated co morbid disease. To evaluate the actual disease pattern a large scale study is required to find the outcome of haemodialysis patients.DOI: http://dx.doi.org/10.3329/kyamcj.v2i2.13262KYAMC Journal Vol.2(2) January 2012, 182-186


2019 ◽  
Vol 20 (14) ◽  
pp. 3393 ◽  
Author(s):  
Keiichiro Matoba ◽  
Yusuke Takeda ◽  
Yosuke Nagai ◽  
Daiji Kawanami ◽  
Kazunori Utsunomiya ◽  
...  

Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease (ESRD) and is therefore a major burden on the healthcare system. Patients with DKD are highly susceptible to developing cardiovascular disease, which contributes to increased morbidity and mortality rates. While progress has been made to inhibit the acceleration of DKD, current standards of care reduce but do not eliminate the risk of DKD. There is growing appreciation for the role of inflammation in modulating the process of DKD. The focus of this review is on providing an overview of the current status of knowledge regarding the pathologic roles of inflammation in the development of DKD. Finally, we summarize recent therapeutic advances to prevent DKD, with a focus on the anti-inflammatory effects of newly developed agents.


2019 ◽  
Vol 20 (15) ◽  
pp. 3668 ◽  
Author(s):  
Elena Oliva-Damaso ◽  
Nestor Oliva-Damaso ◽  
Francisco Rodriguez-Esparragon ◽  
Juan Payan ◽  
Eduardo Baamonde-Laborda ◽  
...  

Asymmetric dimethylarginine (ADMA) and its enantiomer, Symmetric dimethylarginine (SDMA), are naturally occurring amino acids that were first isolated and characterized in human urine in 1970. ADMA is the most potent endogenous inhibitor of nitric oxide synthase (NOS), with higher levels in patients with end-stage renal disease (ESRD). ADMA has shown to be a significant predictor of cardiovascular outcome and mortality among dialysis patients. On the other hand, although initially SDMA was thought to be an innocuous molecule, we now know that it is an outstanding marker of renal function both in human and in animal models, with ESRD patients on dialysis showing the highest SDMA levels. Today, we know that ADMA and SDMA are not only uremic toxins but also independent risk markers for mortality and cardiovascular disease (CVD). In this review, we summarize the role of both ADMA and SDMA in chronic kidney disease along with other cardiovascular risk factors.


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