scholarly journals P1808INHIBITION OF MIR-155 IMPROVES PROGNOSIS IN AN EXPERIMENTAL FSGS MOUSE MODEL BY REGULATING AUTOPHAGY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yu Zhang ◽  
Jie Wang ◽  
Jianhua Zhou
Keyword(s):  
Glomerular Diseases ◽  
Protein Excretion ◽  
Podocyte Loss ◽  
Associated Proteins ◽  
Methenamine Silver ◽  
Stage Renal Disease ◽  
End Stage ◽  
Masson Trichrome Staining ◽  
Insight Into

Abstract Background and Aims Focal segmental glomerulosclerosis (FSGS), a podocytopathy, is one of the most common primary glomerular diseases causing end-stage renal disease in children. Its mechanisms remain unclear and the effective treatment lacks. MiR-155 is a typical multifunctional miRNA, which serves a crucial role in the regulation of numerous vessel cells. The present study aimed to investigate the role of miR-155 in the pathogenesis of FSGS. Method A FSGS model was establishe by injection of adriamycin in miR-155 knockout mice. Renal pathological changes were observed by Periodic Schiff-Methenamine Silver staining and Masson trichrome staining. Podocyte morphology and autophagosomes were examined with electron microscopy. Podocyte density was estimated by the Weibel-Gomez method. Expression of autophagy markers and apoptosis-associated proteins were analyzed by Western blotting analysis. Results Silencing of miR-155 significantly decreased urinary protein excretion and ameliorated glomerulosclerosis in adriamycin-induced FSGS mice. We found that adriamycin treatment led to fusion of podocyte foot processes, swelling of the podocyte body, dilated mitochondria, and podocyte loss. Inhibition of miR-155 improved podocyte depletion and the above cytopathies induced by adriamycin. In addition, the results also demonstrated that in miR-155 KO mice, the expression of LC3 and ATG5 was increased and the expression of P62 was decreased. Conclusion These suggest that modulated miR-155 can prevent podocyte damage, by regulating the level of autophagy. The present study provides a novel insight into microRNAs as potential therapeutics for the treatment of podocytopathy.

Potential role of extracellular vesicles in the pathophysiology of glomerular diseases

2020 ◽  
Vol 134 (20) ◽  
pp. 2741-2754
Author(s):  
Xia-Qing Li ◽  
Lilach O. Lerman ◽  
Yu Meng
Keyword(s):  
Extracellular Vesicles ◽  
Biological Fluids ◽  
Management Strategies ◽  
Renal Diseases ◽  
Future Research ◽  
Target Cells ◽  
Glomerular Diseases ◽  
Stage Renal Disease ◽  
End Stage

Abstract Extracellular vesicles (EVs) are membrane-bound vesicles released by most cells and are found in diverse biological fluids. The release of EVs provides a new mechanism for intercellular communication, allowing cells to transfer their functional cargoes to target cells. Glomerular diseases account for a large proportion of end-stage renal disease (ESRD) worldwide. In recent years, an increasing number of research groups have focused their effort on identifying the functional role of EVs in renal diseases. However, the involvement of EVs in the pathophysiology of glomerular diseases has not been comprehensively described and discussed. In this review, we first briefly introduce the characteristics of EVs. Then, we describe the involvement of EVs in the mechanisms underlying glomerular diseases, including immunological and fibrotic processes. We also discuss what functions EVs derived from different kidney cells have in glomerular diseases and how EVs exert their effects through different signaling pathways. Furthermore, we summarize recent advances in the knowledge of EV involvement in the pathogenesis of various glomerular diseases. Finally, we propose future research directions for identifying better management strategies for glomerular diseases.

scholarly journals Inherited podocytopathies

2008 ◽  
Vol 136 (Suppl. 4) ◽  
pp. 327-339
Author(s):  
Radovan Bogdanovic
Keyword(s):  
Congenital Nephrotic Syndrome ◽  
Structural Studies ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Glomerular Epithelial Cells ◽  
Causes Of Disease ◽  
Stage Renal Disease ◽  
End Stage ◽  
Made In

Podocytes, the visceral glomerular epithelial cells, are the postmythotic cells that line the outer aspects of the glomerular basement membrane. A number of advances have been made in recent years, linked to the discovery of singlegene defects in hereditary glomerular disease, which highlight the role of these cells in preventing proteinuria. Despite the rarity of hereditary proteinuric syndromes, genetic, biochemical, and structural studies of these diseases have made important contributions to our knowledge of how the normal glomerular filter works and the mechanism of proteinuria. The course of these diseases can vary; some patients present with severe proteinuria and congenital nephrotic syndrome, whereas others have only moderate proteinuria and focal segmental glomerulosclerosis. Regardless of its cause, the disease often progresses to end-stage renal disease. There can be overlap between the diseases: mutations in the same gene can lead to different renal phenotypes. It is important to know that some hereditary podocytopathies respond to therapy, whereas majority does not. For this reason, genetic testing, which is available for some hereditary podocytopathies should be performed whenever possible. This review summarizes recent progress in the eludication of genetic causes of disease and discusses their implication for the understanding of the pathogenic mechanisms which can lead to disruption of the glomerular filtration barrier.

Regulation of TRPV5 and TRPV6 by associated proteins

2006 ◽  
Vol 290 (6) ◽  
pp. F1295-F1302 ◽  
Author(s):  
Stan F. J. van de Graaf ◽  
Joost G. J. Hoenderop ◽  
René J. M. Bindels
Keyword(s):  
Molecular Mechanisms ◽  
Hormonal Control ◽  
Trp Channel ◽  
Intestinal Lumen ◽  
Blood Compartment ◽  
Associated Proteins ◽  
The Relationship ◽  
Insight Into ◽  
Prime Target

The epithelial Ca2+ channels TRPV5 and TRPV6 are the most Ca2+-selective members of the TRP channel superfamily. These channels are the prime target for hormonal control of the active Ca2+ flux from the urine space or intestinal lumen to the blood compartment. Insight into their regulation is, therefore, pivotal in our understanding of the (patho)physiology of Ca2+ homeostasis. The recent elucidation of TRPV5/6-associated proteins has provided new insight into the molecular mechanisms underlying the regulation of these channels. In this review, we describe the various means of TRPV5/6 regulation, the role of channel-associated proteins herein, and the relationship between both processes.

The Potential Role of Catheter-Based Renal Sympathetic Denervation in Chronic and End-Stage Kidney Disease

2016 ◽  
Vol 21 (4) ◽  
pp. 344-352 ◽  
Author(s):  
Yusuke Sata ◽  
Markus P. Schlaich
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Kidney Disease ◽  
End Stage Renal Disease ◽  
Renal Denervation ◽  
Potential Role ◽  
Stage Renal Disease ◽  
End Stage ◽  
Renal Sympathetic

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.

scholarly journals Successful multiple-exchange peritoneal dialysis in a patient with severe hematological toxicity by methotrexate: case report and literature review

2019 ◽  
Vol 41 (3) ◽  
pp. 427-432 ◽  
Author(s):  
Arbey Aristizabal-Alzate ◽  
John Fredy Nieto-Rios ◽  
Catalina Ocampo-Kohn ◽  
Lina Maria Serna-Higuita ◽  
Diana Carolina Bello-Marquez ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Therapeutic Option ◽  
Supportive Therapy ◽  
Hematological Toxicity ◽  
High Morbidity ◽  
Multiple Exchange ◽  
Severe Pancytopenia ◽  
Stage Renal Disease ◽  
End Stage

Abstract Methotrexate is an effective medication to control several diseases; however, it can be very toxic, being myelosuppression one of its main adverse effects, which increases in severity and frequency in patients with renal failure. We present the case of a 68-year-old man with chronic, end-stage renal disease associated with ANCA vasculitis, under treatment with peritoneal dialysis, who received the medication at a low dose, indicated by disease activity, which presented as a complication with severe pancytopenia with mucositis that improved with support measures and multiple-exchange peritoneal dialysis. We reviewed 20 cases published to date of pancytopenia associated with methotrexate in patients on dialysis and found high morbidity and mortality, which is why its use in this type of patient is not recommended. However, when this complication occurs, a therapeutic option could be the use of multiple-exchange peritoneal dialysis in addition to supportive therapy for drug-related toxicity, although it is recognized that studies are required to show the role of multiple-exchange peritoneal dialysis in the removal of this medication.

Recent Advances in the Management of the Infant, Child, and Adolescent With Chronic Renal Failure

1990 ◽  
Vol 11 (9) ◽  
pp. 277-282
Author(s):  
Richard N. Fine
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Quarter Century ◽  
Irreversible Reduction ◽  
Age Limits ◽  
Stage Renal Disease ◽  
End Stage

The prognosis of the infant, child, or adolescent with chronic renal failure, defined as an irreversible reduction in glomerular filtration rate, has improved during the past quarter century because of the use of dialysis and renal transplantation. These have prolonged lives in previously fatal situations. Because the potential not only to sustain life but also to effect full rehabilitation exists with the introduction of these treatments, it is now imperative that the multisystem consequences of uremia be either minimized or totally avoided in the pediatric patient with chronic renal failure. The role of the pediatrician in managing the infant, child, or adolescent with chronic renal failure should be directed toward minimizing the potentially devastating consequences of uremia so that the patient is in optimal clinical condition when end stage renal disease occurs. INCIDENCE It is difficult to know the incidence and prevalence of chronic renal failure and end stage renal disease in children. Surveys in Europe and North America have been conducted to obtain precise information regarding these issues; not only have the definitions included in these surveys differed, but the upper and lower age limits defining pediatric patients have not been uniform. The available data suggest a prevalence of chronic renal failure of 18.5 per 1 million child population and an incidence of end stage renal disease of from 3 to 6 children per 1 million total population.

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