scholarly journals Skeletal Muscle Atrophy in Chronic Kidney Disease (CKD)

2020 ◽  
Vol 3 ◽  
Author(s):  
Javier Perez ◽  
Sharon Moe ◽  
Neal Chen ◽  
Keith Avin
Keyword(s):  
Skeletal Muscle ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Atrophy ◽  
Meta Analysis ◽  
Skeletal Muscle Atrophy ◽  
Muscle Dysfunction ◽  
Activity Levels ◽  
Western Blots ◽  
Pyruvate Oxidation

Background:   Skeletal muscle atrophy and dysfunction occur with chronic kidney disease (CKD) progression leading to morbidity, mortality, and falls. Skeletal muscle dysfunction may be due to impaired fatty acid (FA) oxidation and enhanced pyruvate oxidation as demonstrated in preliminary metabolomic data. We performed multiple techniques to assess the extent of muscle dysfunction and associated pathways, including: systematic review and meta-analysis,  assays of disease progression and FA metabolism, expression of markers associated with skeletal muscle FA metabolism and pyruvate oxidation.     Methods:   Meta-analysis: Multiple databases were used to identify relevant studies of muscle atrophy in preclinical and clinical models.   Experimental Study: 1)CKD rats and 2)Normal littermates (N=12/gr) at 35 weeks. Extensor digitorum longus (EDL) and soleus were harvested at sacrifice. Serum Biochemistry: Plasma BUN, calcium and phosphorus were analyzed using colorimetric assays. Carnitine Assay: Plasma carnitine levels was measured using ELISA kit. Protein Expression: Western blots with the lysate of EDL and soleus to determine the activity levels of PDH and PDK4.    Results:    A total of 4685 studies were screened in the meta-analysis, of which 646 were relevant. Subsequent steps are to perform full text review and data extraction. Animal studies: BUN and phosphorus were significantly increased in CKD compared to normal. Carnitine levels were significantly decreased in CKD rats compared to normal. PDH was not significantly different in the EDL or soleus. PDK4 is yet to be performed.     Conclusions:   The extent to which muscle atrophy occurs will be identified in the meta-analysis. Elevated BUN confirmed disease and carnitine assay confirmed low carnitine levels in CKD. Identifying low carnitine has led to an interventional study of carnitine supplementation to determine if there was improved FA oxidation. Testing of PDK4 is needed to determine significance of pyruvate regulation. Reviewing the literature and understanding the mechanism of skeletal muscle atrophy in CKD will allow future targeted therapeutics. 

The Effect of Iron on Skeletal Muscle Atrophy in Chronic Kidney Disease

2017 ◽  
Vol 112 ◽  
pp. 204-205
Author(s):  
Yuya Horinouchi ◽  
Yasumasa Ikeda ◽  
Hirofumi Hamano ◽  
Masaki Imanishi ◽  
Yuki Izawa-Ishizawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy

scholarly journals Hyperphosphatemia Contributes to Skeletal Muscle Atrophy in Chronic Kidney Disease

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Kylie Heitman ◽  
Brian Czaya ◽  
Beatrice Richter ◽  
Isaac Campos ◽  
Christopher Yanucil ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy

scholarly journals Hydrogen sulfide alleviates hyperhomocysteinemia-mediated skeletal muscle atrophy via mitigation of oxidative and endoplasmic reticulum stress injury

2018 ◽  
Vol 315 (5) ◽  
pp. C609-C622 ◽  
Author(s):  
Avisek Majumder ◽  
Mahavir Singh ◽  
Jyotirmaya Behera ◽  
Nicholas T. Theilen ◽  
Akash K. George ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Endoplasmic Reticulum ◽  
Hydrogen Sulfide ◽  
Er Stress ◽  
Muscle Atrophy ◽  
C2c12 Cells ◽  
Skeletal Muscle Atrophy ◽  
Stress Injury ◽  
Western Blots

Although hyperhomocysteinemia (HHcy) occurs because of the deficiency in cystathionine-β-synthase (CBS) causing skeletal muscle dysfunction, it is still unclear whether this effect is mediated through oxidative stress, endoplasmic reticulum (ER) stress, or both. Nevertheless, there is no treatment option available to improve HHcy-mediated muscle injury. Hydrogen sulfide (H2S) is an antioxidant compound, and patients with CBS mutation do not produce H2S. In this study, we hypothesized that H2S mitigates HHcy-induced redox imbalance/ER stress during skeletal muscle atrophy via JNK phosphorylation. We used CBS+/−mice to study HHcy-mediated muscle atrophy, and treated them with sodium hydrogen sulfide (NaHS; an H2S donor). Proteins and mRNAs were examined by Western blots and quantitative PCR. Proinflammatory cytokines were also measured. Muscle mass and strength were studied via fatigue susceptibility test. Our data revealed that HHcy was detrimental to skeletal mass, particularly gastrocnemius and quadriceps muscle weight. We noticed that oxidative stress was reversed by NaHS in homocysteine (Hcy)-treated C2C12 cells. Interestingly, ER stress markers (GRP78, ATF6, pIRE1α, and pJNK) were elevated in vivo and in vitro, and NaHS mitigated these effects. Additionally, we observed that JNK phosphorylation was upregulated in C2C12 after Hcy treatment, but NaHS could not reduce this effect. Furthermore, inflammatory cytokines IL-6 and TNF-α were higher in plasma from CBS as compared with wild-type mice. FOXO1-mediated Atrogin-1 and MuRF-1 upregulation were attenuated by NaHS. Functional studies revealed that NaHS administration improved muscle fatigability in CBS+/−mice. In conclusion, our work provides evidence that NaHS is beneficial in mitigating HHcy-mediated skeletal injury incited by oxidative/ER stress responses.

scholarly journals Sarcopenia in chronic kidney disease – A brief review

2021 ◽  
Vol 35 (2) ◽  
Author(s):  
Beatriz Donato ◽  
◽  
Catarina Teixeira ◽  
Sónia Velho ◽  
Edgar Almeida ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Mass ◽  
Physical Performance ◽  
Functional Independence ◽  
Muscle Dysfunction ◽  
Skeletal Muscle Dysfunction ◽  
Age Related ◽  
The Impact

Sarcopenia is a progressive age -related loss of muscle mass associated with a decline in muscle function and physical performance. Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. Indeed, with the progression of chronic kidney disease, skeletal muscle dysfunction contributes to mobility limitation, loss of functional independence, and vulnerability to disease complications. There is a lack of robust data on the negative effect of the impact of kidney disease on skeletal muscle dysfunction, as well as on screening and treatment strategies that can be used in clinical practice to prevent functional decline and disability. Therefore, sarcopenia may be an underestimated condition with major implications for people with chronic kidney disease, even before the start of dialysis, which makes research into this topic necessary. The purpose of this review is to expand on some fundamental topics of sarcopenia, with an emphasis on the setting of chronic kidney disease patients.

scholarly journals Prevention of Doxorubicin-Induced Autophagy Attenuates Oxidative Stress and Skeletal Muscle Dysfunction

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 263 ◽  
Author(s):  
Vivian Doerr ◽  
Ryan N. Montalvo ◽  
Oh Sung Kwon ◽  
Erin E. Talbert ◽  
Brian A. Hain ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Dominant Negative ◽  
Skeletal Muscle Atrophy ◽  
Muscle Dysfunction ◽  
Related Factor ◽  
Skeletal Muscle Dysfunction ◽  
Dominant Negative Mutation

Clinical use of the chemotherapeutic doxorubicin (DOX) promotes skeletal muscle atrophy and weakness, adversely affecting patient mobility and strength. Although the mechanisms responsible for DOX-induced skeletal muscle dysfunction remain unclear, studies implicate the significant production of reactive oxygen species (ROS) in this pathology. Supraphysiological ROS levels can enhance protein degradation via autophagy, and it is established that DOX upregulates autophagic signaling in skeletal muscle. To determine the precise contribution of accelerated autophagy to DOX-induced skeletal muscle dysfunction, we inhibited autophagy in the soleus via transduction of a dominant negative mutation of the autophagy related 5 (ATG5) protein. Targeted inhibition of autophagy prevented soleus muscle atrophy and contractile dysfunction acutely following DOX administration, which was associated with a reduction in mitochondrial ROS and maintenance of mitochondrial respiratory capacity. These beneficial modifications were potentially the result of enhanced transcription of antioxidant response element-related genes and increased antioxidant capacity. Specifically, our results showed significant upregulation of peroxisome proliferator-activated receptor gamma co-activator 1-alpha, nuclear respiratory factor-1, nuclear factor erythroid-2-related factor-2, nicotinamide-adenine dinucleotide phosphate quinone dehydrogenase-1, and catalase in the soleus with DOX treatment when autophagy was inhibited. These findings establish a significant role of autophagy in the development of oxidative stress and skeletal muscle weakness following DOX administration.

scholarly journals Skeletal muscle wasting in chronic kidney disease: the emerging role of microRNAs

2019 ◽  
Vol 35 (9) ◽  
pp. 1469-1478 ◽  
Author(s):  
Kate A Robinson ◽  
Luke A Baker ◽  
Matthew P M Graham-Brown ◽  
Emma L Watson
Keyword(s):  
Skeletal Muscle ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Muscle Wasting ◽  
Muscle Growth ◽  
Exciting Field ◽  
Skeletal Muscle Wasting ◽  
And Function

Abstract Skeletal muscle wasting is a common complication of chronic kidney disease (CKD), characterized by the loss of muscle mass, strength and function, which significantly increases the risk of morbidity and mortality in this population. Numerous complications associated with declining renal function and lifestyle activate catabolic pathways and impair muscle regeneration, resulting in substantial protein wasting. Evidence suggests that increasing skeletal muscle mass improves outcomes in CKD, making this a clinically important research focus. Despite extensive research, the pathogenesis of skeletal muscle wasting is not completely understood. It is widely recognized that microRNAs (miRNAs), a family of short non-coding RNAs, are pivotal in the regulation of skeletal muscle homoeostasis, with significant roles in regulating muscle growth, regeneration and metabolism. The abnormal expression of miRNAs in skeletal muscle during disease has been well described in cellular and animal models of muscle atrophy, and in recent years, the involvement of miRNAs in the regulation of muscle atrophy in CKD has been demonstrated. As this exciting field evolves, there is emerging evidence for the involvement of miRNAs in a beneficial crosstalk system between skeletal muscle and other organs that may potentially limit the progression of CKD. In this article, we describe the pathophysiological mechanisms of muscle wasting and explore the contribution of miRNAs to the development of muscle wasting in CKD. We also discuss advances in our understanding of miRNAs in muscle–organ crosstalk and summarize miRNA-based therapeutics currently in clinical trials.

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