MOLECULAR ASPECTS OF SARCOPENIA PATHOGENESIS IN CHRONOC KIDNEY DISEASE: INTEGRATED ROLE OF mTOR

2018 ◽  
Vol 22 (5) ◽  
pp. 9-16 ◽  
Author(s):  
M. Z. Gasanov
Keyword(s):  
Kidney Disease ◽  
Muscle Mass ◽  
Protein Metabolism ◽  
Mammalian Target Of Rapamycin ◽  
Healthy Person ◽  
Scientific Review ◽  
Cytoskeleton Organization ◽  
Molecular Aspects ◽  
End Stage

In recent decades, the main pathogenetic mechanisms for maintaining muscle mass and strength have been discovered. Most of the scientific papers on the molecular aspects of the  pathogenesis of sarcopenia were focused on the Akt-signaling  pathway. The subject of the study were people of elderly and senile  age, immobilized patients, patients with CKD 1-4 stages, animals. However, recently more attention has been paid to the role  of protein – the mammalian target of rapamycin mTOR. It seems to be a key link in the control of muscle mass and is a promising  marker in understanding the mechanisms of the pathogenesis of  sarcopenia. Its importance in protein metabolism in patients with  end stage kidney disease is not studied and requires further research. The presented scientific review contains  information on the role of mTOR and its components – mTORC1 and mTORC2 in maintaining muscle mass and strength in a healthy  person and in the formation of sarcopenia in patients with CKD. The  general aid of mTORC1 complex is regulation of protein production  which is necessary for cell growth and differentiation. mTORC2  complex functions are not enough studied. It is established that it  plays important role in such biological processes as cytoskeleton  organization, intracellular homeostasis maintaining, so it provides  cell resistance and cell survivability in negative external and internal  impulses. mTOR protein can be considered as promising molecular  marker in diagnostics of protein metabolism early disturbances in  patients with CKD and also as additory factor of sarcopenia severity assessment.

scholarly journals Optimal Protein Intake in Pre-Dialysis Chronic Kidney Disease Patients with Sarcopenia: An Overview

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1205
Author(s):  
Yoshitaka Isaka
Keyword(s):  
Chronic Kidney Disease ◽  
High Risk ◽  
Kidney Disease ◽  
Muscle Mass ◽  
Exercise Therapy ◽  
Protein Intake ◽  
Renin Angiotensin System ◽  
Protein Restriction ◽  
Ckd Stage ◽  
End Stage

Multi-factors, such as anorexia, activation of renin-angiotensin system, inflammation, and metabolic acidosis, contribute to malnutrition in chronic kidney disease (CKD) patients. Most of these factors, contributing to the progression of malnutrition, worsen as CKD progresses. Protein restriction, used as a treatment for CKD, can reduce the risk of CKD progression, but may worsen the sarcopenia, a syndrome characterized by a progressive and systemic loss of muscle mass and strength. The concomitant rate of sarcopenia is higher in CKD patients than in the general population. Sarcopenia is also associated with mortality risk in CKD patients. Thus, it is important to determine whether protein restriction should be continued or loosened in CKD patients with sarcopenia. We may prioritize protein restriction in CKD patients with a high risk of end-stage kidney disease (ESKD), classified to stage G4 to G5, but may loosen protein restriction in ESKD-low risk CKD stage G3 patients with proteinuria <0.5 g/day, and rate of eGFR decline <3.0 mL/min/1.73 m2/year. However, the effect of increasing protein intake alone without exercise therapy may be limited in CKD patients with sarcopenia. The combination of exercise therapy and increased protein intake is effective in improving muscle mass and strength in CKD patients with sarcopenia. In the case of loosening protein restriction, it is safe to avoid protein intake of more than 1.5 g/kgBW/day. In CKD patients with high risk in ESKD, 0.8 g/kgBW/day may be a critical point of protein intake.

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 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
Keyword(s):  
Kidney Disease ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Renal Diseases ◽  
Hypertensive Nephropathy ◽  
Mesenchymal Transition ◽  
Afferent Arterioles ◽  
Stage Renal Disease ◽  
End Stage

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.

scholarly journals Advocacy for renal replacement therapy: the role of renal registries

2020 ◽  
Vol 13 (5) ◽  
pp. 742-744
Author(s):  
Cecile Couchoud ◽  
Mohamed Benghanem Gharbi
Keyword(s):  
Renal Replacement Therapy ◽  
Kidney Disease ◽  
Replacement Therapy ◽  
South African ◽  
Limited Resource ◽  
Service Planning ◽  
End Stage Kidney Disease ◽  
End Stage ◽  
Resource Environment

Abstract The paper by Jardine et al. reporting results from the South African Renal Registry describes a 2-fold success. First, even in a limited-resource environment, survival of patients on renal replacement therapy (RRT) is favourable. Secondly, this information is available because a few years ago, South African nephrologists started a renal registry. These successes cannot conceal, however, that numerous patients are not offered RRT. Robust health information systems make it possible to define chronic kidney disease and end-stage kidney disease (ESKD) burdens, guide resource allocation, inform service planning and enable policy. Registries can highlight inequitable RRT access and help support advocacy in favour of additional resources for ESKD care.

scholarly journals P0921ROLE OF UREMIC TOXIN, INDOXYL SULFATE IN SARCOPENIA OF NONDIALYSIS DEPENDENT-CHRONIC KIDNEY DISEASE PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Jun Chul Kim ◽  
Seok Hui Kang ◽  
Miyeun Han ◽  
Su-Hyun Kim ◽  
Ran-Hui Cha ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Mass ◽  
Bioelectrical Impedance ◽  
Impedance Analysis ◽  
Indoxyl Sulfate ◽  
High Rate ◽  
Uremic Toxin ◽  
Inverse Association

Abstract Background and Aims Sarcopenia in patients with chronic kidney disease (CKD) is highly prevalent and leads to high rate of morbidity and mortality. The role of indoxyl sulfate (IS) to develop muscle wasting has been researched and proved in several animal model studies. However, there is no human data showing this relationship in CKD population. The aim of the present study was to evaluate the association between serum IS levels and each component of sarcopenia in nondialysis dependent-CKD (NDD-CKD) patients. Method We enrolled 150 NDD-CKD adult patients from 6 medical centers and collected data of demographics, blood chemistry such as indoxyl sulfate, interleukin (IL)-6, and estimated glomerular filtration rate using MDRD equation (eGFR), and body mass index (BMI, kg/m2). We also measured hand-grip strength (HGS, kg), walking speed (WS, m/s), skeletal muscle mass (SMM, kg) by bioelectrical impedance analysis (BIA). Results The numbers of male sex was 97 (64.7%). Mean age was 63.7±10.8 years old. The numbers of patients with diabetes mellitus was 77 (52.0%). Charlson comorbidity index (CCI) score was 3.9 ± 1.9. The stage of CKD ranged from 3 to 5 (eGFR=33.7±12.0 ml/min/1.73m2, mean±SD). Correlation coefficients with indoxyl sulfate levels were 0.211 for serum IL-6 level (P = 0.010), -0.212 for HGS (P = 0.009), -0.188 for WS (P = 0.021), -0.237 for SMM (P = 0.004), and -0.168 for BMI (P = 0.041), respectively. Correlation analysis showed that indoxyl sulfate levels had inverse association significantly with HGS, WS, SMM, and BMI and were positively associated with serum IL-6 levels. Conclusion Our study shows that higher serum indoxyl sulfate level was significantly associated with lower levels of muscle mass, strength, and physical performance function and higher inflammation status in non-dialysis dependent CKD patients. We suggest that the role of AST120 in prevention or treatment of sarcopenia be studied in this CKD population.

scholarly journals Role of Epigallocatechin Gallate in Glucose, Lipid, and Protein Metabolism and L-Theanine in the Metabolism-Regulatory Effects of Epigallocatechin Gallate

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4120
Author(s):  
Ling Lin ◽  
Li Zeng ◽  
An Liu ◽  
Dongyin Yuan ◽  
Yingqi Peng ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Insulin Receptor ◽  
Protein Metabolism ◽  
Glycogen Synthase ◽  
Mammalian Target Of Rapamycin ◽  
Epigallocatechin Gallate ◽  
Control Group ◽  
Nutrient Metabolism ◽  
Regulatory Effects

Epigallocatechin gallate (EGCG) and L-theanine (LTA) are important bioactive components in tea that have shown promising effects on nutrient metabolism. However, whether EGCG alone or combined with LTA can regulate the glucose, lipid, and protein metabolism of healthy rats remains unclear. Therefore, we treated healthy rats with EGCG or the combination of EGCG and LTA (EGCG+LTA) to investigate the effects of EGCG on nutrient metabolism and the role of LTA in the metabolism-regulatory effects of EGCG. The results showed that compared with the control group, EGCG activated insulin and AMP-activated protein kinase (AMPK) signals, thus regulating glucose, lipid, and protein metabolism. Compared with EGCG, EGCG+LTA enhanced hepatic and muscle glycogen levels and suppressed phosphorylation of AMPK, glycogen synthase 2, mammalian target of rapamycin, and ribosomal protein S6 kinase. In addition, EGCG+LTA inhibited the expression of liver kinase B1, insulin receptor and insulin receptor substrate, and promoted the phosphorylation level of acetyl-CoA carboxylase. Furthermore, both EGCG and EGCG+LTA were harmless for young rats. In conclusion, EGCG activated AMPK and insulin pathways, thereby promoting glycolysis, glycogen, and protein synthesis and inhibiting fatty acid (FA) and cholesterol synthesis. However, LTA cooperated with EGCG to promote glycogen metabolism and suppressed the effect EGCG on FA and protein synthesis via AMPK signals.

scholarly journals The role of psychological factors in fatigue among end-stage kidney disease patients: a critical review

2016 ◽  
pp. sfw113 ◽  
Author(s):  
Federica Picariello ◽  
Rona Moss-Morris ◽  
Iain C. Macdougall ◽  
Joseph Chilcot
Keyword(s):  
Kidney Disease ◽  
Critical Review ◽  
Psychological Factors ◽  
End Stage Kidney Disease ◽  
End Stage

scholarly journals Unraveling the Role of Inflammation in the Pathogenesis of Diabetic Kidney Disease

2019 ◽  
Vol 20 (14) ◽  
pp. 3393 ◽  
Author(s):  
Keiichiro Matoba ◽  
Yusuke Takeda ◽  
Yosuke Nagai ◽  
Daiji Kawanami ◽  
Kazunori Utsunomiya ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Mortality Rates ◽  
Standards Of Care ◽  
Current Status ◽  
Diabetic Kidney ◽  
Stage Renal Disease ◽  
End Stage ◽  
Current Standards

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.

scholarly journals Asymmetric (ADMA) and Symmetric (SDMA) Dimethylarginines in Chronic Kidney Disease: A Clinical Approach

2019 ◽  
Vol 20 (15) ◽  
pp. 3668 ◽  
Author(s):  
Elena Oliva-Damaso ◽  
Nestor Oliva-Damaso ◽  
Francisco Rodriguez-Esparragon ◽  
Juan Payan ◽  
Eduardo Baamonde-Laborda ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Clinical Approach ◽  
Risk Markers ◽  
Naturally Occurring ◽  
Stage Renal Disease ◽  
End Stage ◽  
Oxide Synthase ◽  
Esrd Patients

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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