Pathophysiological mechanisms leading to muscle loss in chronic kidney disease
Loss of muscle proteins is a deleterious consequence of chronic kidney disease (CKD) that causes a decrease in muscle strength and function, and can lead to a reduction in quality of life and increased risk of morbidity and mortality. The effectiveness of current treatment strategies in preventing o...
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Veröffentlicht in: | Nature reviews. Nephrology 2022-03, Vol.18 (3), p.138-152 |
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description | Loss of muscle proteins is a deleterious consequence of chronic kidney disease (CKD) that causes a decrease in muscle strength and function, and can lead to a reduction in quality of life and increased risk of morbidity and mortality. The effectiveness of current treatment strategies in preventing or reversing muscle protein losses is limited. The limitations largely stem from the systemic nature of diseases such as CKD, which stimulate skeletal muscle protein degradation pathways while simultaneously activating mechanisms that impair muscle protein synthesis and repair. Stimuli that initiate muscle protein loss include metabolic acidosis, insulin and IGF1 resistance, changes in hormones, cytokines, inflammatory processes and decreased appetite. A growing body of evidence suggests that signalling molecules secreted from muscle can enter the circulation and subsequently interact with recipient organs, including the kidneys, while conversely, pathological events in the kidney can adversely influence protein metabolism in skeletal muscle, demonstrating the existence of crosstalk between kidney and muscle. Together, these signals, whether direct or indirect, induce changes in the levels of regulatory and effector proteins via alterations in mRNAs, microRNAs and chromatin epigenetic responses. Advances in our understanding of the signals and processes that mediate muscle loss in CKD and other muscle wasting conditions will support the future development of therapeutic strategies to reduce muscle loss.
Loss of muscle protein is a deleterious consequence of chronic kidney disease (CKD) that results in decreased muscle strength and function. This Review summarizes the cellular mechanisms that lead to reductions in muscle protein in patients with CKD and highlights commonalities with other catabolic conditions such as cancer and diabetes.
Key points
Loss of muscle mass in patients with chronic kidney disease (CKD) leads to frailty and is associated with reduced quality of life and increased risks of morbidity and mortality.
In healthy individuals, muscle mass is maintained by a balance of processes — including protein synthesis, protein degradation, energy production and utilization — that support muscle growth and turnover.
In patients with CKD and other wasting conditions, pathophysiological changes at the cellular and organ system levels disrupt muscle proteostasis and cellular bioenergetics processes, suppress muscle repair and protein synthesis pathways, and i |
doi_str_mv | 10.1038/s41581-021-00498-0 |
format | Article |
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Loss of muscle protein is a deleterious consequence of chronic kidney disease (CKD) that results in decreased muscle strength and function. This Review summarizes the cellular mechanisms that lead to reductions in muscle protein in patients with CKD and highlights commonalities with other catabolic conditions such as cancer and diabetes.
Key points
Loss of muscle mass in patients with chronic kidney disease (CKD) leads to frailty and is associated with reduced quality of life and increased risks of morbidity and mortality.
In healthy individuals, muscle mass is maintained by a balance of processes — including protein synthesis, protein degradation, energy production and utilization — that support muscle growth and turnover.
In patients with CKD and other wasting conditions, pathophysiological changes at the cellular and organ system levels disrupt muscle proteostasis and cellular bioenergetics processes, suppress muscle repair and protein synthesis pathways, and increase protein degradation.
To date, efforts to develop effective treatments that counter the pathophysiological changes in CKD and ameliorate loss of muscle mass and function have met with limited success.
Skeletal muscles can secrete a variety of signalling molecules that circulate and interact with recipient organs, including the kidneys; conversely, pathological events in the kidney can adversely influence protein metabolism in skeletal muscle, highlighting the importance of crosstalk between kidney and muscle.
Emerging therapies, including microRNA therapeutics and approaches to target specific pathways involved in kidney–muscle crosstalk, have potential to induce positive changes in muscle cell signalling to maintain muscle homeostasis while simultaneously improving kidney bioenergetics and kidney function.</description><identifier>ISSN: 1759-5061</identifier><identifier>EISSN: 1759-507X</identifier><identifier>DOI: 10.1038/s41581-021-00498-0</identifier><identifier>PMID: 34750550</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/4022 ; 692/4022/1585/104 ; Amino acids ; Atrophy ; Body composition ; Chronic illnesses ; Humans ; Insulin ; Kidney diseases ; Medicine ; Medicine & Public Health ; Metabolism ; MicroRNAs - metabolism ; Morbidity ; Mortality ; Muscle contraction ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - pathology ; Muscular Atrophy ; Musculoskeletal system ; Nephrology ; Protein synthesis ; Proteins ; Quality of Life ; Renal Insufficiency, Chronic - complications ; Renal Insufficiency, Chronic - metabolism ; Review Article</subject><ispartof>Nature reviews. Nephrology, 2022-03, Vol.18 (3), p.138-152</ispartof><rights>Springer Nature Limited 2021</rights><rights>2021. Springer Nature Limited.</rights><rights>Springer Nature Limited 2021.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-8163e63249a2ab59d48aac6bc74083642697de23279b49f49042d5b456a3244b3</citedby><cites>FETCH-LOGICAL-c375t-8163e63249a2ab59d48aac6bc74083642697de23279b49f49042d5b456a3244b3</cites><orcidid>0000-0003-0893-0723</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34750550$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Xiaonan H.</creatorcontrib><creatorcontrib>Mitch, William E.</creatorcontrib><creatorcontrib>Price, S. Russ</creatorcontrib><title>Pathophysiological mechanisms leading to muscle loss in chronic kidney disease</title><title>Nature reviews. Nephrology</title><addtitle>Nat Rev Nephrol</addtitle><addtitle>Nat Rev Nephrol</addtitle><description>Loss of muscle proteins is a deleterious consequence of chronic kidney disease (CKD) that causes a decrease in muscle strength and function, and can lead to a reduction in quality of life and increased risk of morbidity and mortality. The effectiveness of current treatment strategies in preventing or reversing muscle protein losses is limited. The limitations largely stem from the systemic nature of diseases such as CKD, which stimulate skeletal muscle protein degradation pathways while simultaneously activating mechanisms that impair muscle protein synthesis and repair. Stimuli that initiate muscle protein loss include metabolic acidosis, insulin and IGF1 resistance, changes in hormones, cytokines, inflammatory processes and decreased appetite. A growing body of evidence suggests that signalling molecules secreted from muscle can enter the circulation and subsequently interact with recipient organs, including the kidneys, while conversely, pathological events in the kidney can adversely influence protein metabolism in skeletal muscle, demonstrating the existence of crosstalk between kidney and muscle. Together, these signals, whether direct or indirect, induce changes in the levels of regulatory and effector proteins via alterations in mRNAs, microRNAs and chromatin epigenetic responses. Advances in our understanding of the signals and processes that mediate muscle loss in CKD and other muscle wasting conditions will support the future development of therapeutic strategies to reduce muscle loss.
Loss of muscle protein is a deleterious consequence of chronic kidney disease (CKD) that results in decreased muscle strength and function. This Review summarizes the cellular mechanisms that lead to reductions in muscle protein in patients with CKD and highlights commonalities with other catabolic conditions such as cancer and diabetes.
Key points
Loss of muscle mass in patients with chronic kidney disease (CKD) leads to frailty and is associated with reduced quality of life and increased risks of morbidity and mortality.
In healthy individuals, muscle mass is maintained by a balance of processes — including protein synthesis, protein degradation, energy production and utilization — that support muscle growth and turnover.
In patients with CKD and other wasting conditions, pathophysiological changes at the cellular and organ system levels disrupt muscle proteostasis and cellular bioenergetics processes, suppress muscle repair and protein synthesis pathways, and increase protein degradation.
To date, efforts to develop effective treatments that counter the pathophysiological changes in CKD and ameliorate loss of muscle mass and function have met with limited success.
Skeletal muscles can secrete a variety of signalling molecules that circulate and interact with recipient organs, including the kidneys; conversely, pathological events in the kidney can adversely influence protein metabolism in skeletal muscle, highlighting the importance of crosstalk between kidney and muscle.
Emerging therapies, including microRNA therapeutics and approaches to target specific pathways involved in kidney–muscle crosstalk, have potential to induce positive changes in muscle cell signalling to maintain muscle homeostasis while simultaneously improving kidney bioenergetics and kidney function.</description><subject>692/4022</subject><subject>692/4022/1585/104</subject><subject>Amino acids</subject><subject>Atrophy</subject><subject>Body composition</subject><subject>Chronic illnesses</subject><subject>Humans</subject><subject>Insulin</subject><subject>Kidney diseases</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolism</subject><subject>MicroRNAs - metabolism</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Muscle contraction</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - pathology</subject><subject>Muscular Atrophy</subject><subject>Musculoskeletal system</subject><subject>Nephrology</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Quality of Life</subject><subject>Renal Insufficiency, Chronic - complications</subject><subject>Renal Insufficiency, Chronic - metabolism</subject><subject>Review Article</subject><issn>1759-5061</issn><issn>1759-507X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kE1LwzAch4Mobk6_gAcJePFSzXubowzfYKgHBW8hTbMts21m0h727Y12TvDgIfwDeX6_JA8ApxhdYkSLq8gwL3CGSFqIySJDe2CMcy4zjvK3_d1e4BE4inGFkBAs54dgRNNAnKMxeHzW3dKvl5vofO0XzugaNtYsdetiE2FtdeXaBew8bPpoagtrHyN0LTTL4Ftn4LurWruBlYtWR3sMDua6jvZkOyfg9fbmZXqfzZ7uHqbXs8zQnHdZgQW1ghImNdEllxUrtDaiNDlDBRWMCJlXllCSy5LJOZOIkYqXjAudQqykE3Ax9K6D_-ht7FTjorF1rVvr-6gIl5wLiZlI6PkfdOX70KbXKSIopgXLGU8UGSgT0geDnat1cI0OG4WR-rKtBtsq2VbfthVKobNtdV82ttpFfvQmgA5ATEftwobfu_-p_QT5jokw</recordid><startdate>20220301</startdate><enddate>20220301</enddate><creator>Wang, Xiaonan H.</creator><creator>Mitch, William E.</creator><creator>Price, S. Russ</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-0893-0723</orcidid></search><sort><creationdate>20220301</creationdate><title>Pathophysiological mechanisms leading to muscle loss in chronic kidney disease</title><author>Wang, Xiaonan H. ; Mitch, William E. ; Price, S. Russ</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-8163e63249a2ab59d48aac6bc74083642697de23279b49f49042d5b456a3244b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>692/4022</topic><topic>692/4022/1585/104</topic><topic>Amino acids</topic><topic>Atrophy</topic><topic>Body composition</topic><topic>Chronic illnesses</topic><topic>Humans</topic><topic>Insulin</topic><topic>Kidney diseases</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolism</topic><topic>MicroRNAs - metabolism</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Muscle contraction</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - pathology</topic><topic>Muscular Atrophy</topic><topic>Musculoskeletal system</topic><topic>Nephrology</topic><topic>Protein synthesis</topic><topic>Proteins</topic><topic>Quality of Life</topic><topic>Renal Insufficiency, Chronic - complications</topic><topic>Renal Insufficiency, Chronic - metabolism</topic><topic>Review Article</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Xiaonan H.</creatorcontrib><creatorcontrib>Mitch, William E.</creatorcontrib><creatorcontrib>Price, S. Russ</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Nature reviews. Nephrology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Xiaonan H.</au><au>Mitch, William E.</au><au>Price, S. Russ</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pathophysiological mechanisms leading to muscle loss in chronic kidney disease</atitle><jtitle>Nature reviews. Nephrology</jtitle><stitle>Nat Rev Nephrol</stitle><addtitle>Nat Rev Nephrol</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>18</volume><issue>3</issue><spage>138</spage><epage>152</epage><pages>138-152</pages><issn>1759-5061</issn><eissn>1759-507X</eissn><abstract>Loss of muscle proteins is a deleterious consequence of chronic kidney disease (CKD) that causes a decrease in muscle strength and function, and can lead to a reduction in quality of life and increased risk of morbidity and mortality. The effectiveness of current treatment strategies in preventing or reversing muscle protein losses is limited. The limitations largely stem from the systemic nature of diseases such as CKD, which stimulate skeletal muscle protein degradation pathways while simultaneously activating mechanisms that impair muscle protein synthesis and repair. Stimuli that initiate muscle protein loss include metabolic acidosis, insulin and IGF1 resistance, changes in hormones, cytokines, inflammatory processes and decreased appetite. A growing body of evidence suggests that signalling molecules secreted from muscle can enter the circulation and subsequently interact with recipient organs, including the kidneys, while conversely, pathological events in the kidney can adversely influence protein metabolism in skeletal muscle, demonstrating the existence of crosstalk between kidney and muscle. Together, these signals, whether direct or indirect, induce changes in the levels of regulatory and effector proteins via alterations in mRNAs, microRNAs and chromatin epigenetic responses. Advances in our understanding of the signals and processes that mediate muscle loss in CKD and other muscle wasting conditions will support the future development of therapeutic strategies to reduce muscle loss.
Loss of muscle protein is a deleterious consequence of chronic kidney disease (CKD) that results in decreased muscle strength and function. This Review summarizes the cellular mechanisms that lead to reductions in muscle protein in patients with CKD and highlights commonalities with other catabolic conditions such as cancer and diabetes.
Key points
Loss of muscle mass in patients with chronic kidney disease (CKD) leads to frailty and is associated with reduced quality of life and increased risks of morbidity and mortality.
In healthy individuals, muscle mass is maintained by a balance of processes — including protein synthesis, protein degradation, energy production and utilization — that support muscle growth and turnover.
In patients with CKD and other wasting conditions, pathophysiological changes at the cellular and organ system levels disrupt muscle proteostasis and cellular bioenergetics processes, suppress muscle repair and protein synthesis pathways, and increase protein degradation.
To date, efforts to develop effective treatments that counter the pathophysiological changes in CKD and ameliorate loss of muscle mass and function have met with limited success.
Skeletal muscles can secrete a variety of signalling molecules that circulate and interact with recipient organs, including the kidneys; conversely, pathological events in the kidney can adversely influence protein metabolism in skeletal muscle, highlighting the importance of crosstalk between kidney and muscle.
Emerging therapies, including microRNA therapeutics and approaches to target specific pathways involved in kidney–muscle crosstalk, have potential to induce positive changes in muscle cell signalling to maintain muscle homeostasis while simultaneously improving kidney bioenergetics and kidney function.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34750550</pmid><doi>10.1038/s41581-021-00498-0</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-0893-0723</orcidid></addata></record> |
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subjects | 692/4022 692/4022/1585/104 Amino acids Atrophy Body composition Chronic illnesses Humans Insulin Kidney diseases Medicine Medicine & Public Health Metabolism MicroRNAs - metabolism Morbidity Mortality Muscle contraction Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Muscular Atrophy Musculoskeletal system Nephrology Protein synthesis Proteins Quality of Life Renal Insufficiency, Chronic - complications Renal Insufficiency, Chronic - metabolism Review Article |
title | Pathophysiological mechanisms leading to muscle loss in chronic kidney disease |
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