{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:06:40Z","timestamp":1790204800439,"version":"4.1.0"},"reference-count":103,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Genoa","award":["Finanziamento di Ateneo 2019"],"award-info":[{"award-number":["Finanziamento di Ateneo 2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Protein energy wasting (PEW) is a common complication both in chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Of note, PEW is one of the stronger predictors of morbidity and mortality in this patient population. The pathogenesis of PEW involves several mechanisms, including anorexia, insulin resistance, acidosis and low-grade inflammation. In addition, \u201csterile\u201d muscle inflammation contributes to PEW at an advanced CKD stage. Both immune and resident muscle cells can activate innate immunity; thus, they have critical roles in triggering \u201csterile\u201d tissue inflammation. Toll-like receptor 4 (TLR4) can detect endogenous danger-associated molecular patterns generated or retained in blood in uremia and induce a sterile muscle inflammatory response via NF-\u03baB in myocytes. In addition, TLR4, though the activation of the NLRP3 inflammasome, links the sensing of metabolic uremic stress in muscle to the activation of pro-inflammatory cascades, which lead to the production of IL-1\u03b2 and IL-18. Finally, uremia-induced accelerated cell senescence is associated with a secretory phenotype that favors fibrosis in muscle. Targeting these innate immune pathways could lead to novel therapies for CKD-related PEW.<\/jats:p>","DOI":"10.3390\/nu15132832","type":"journal-article","created":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T02:09:17Z","timestamp":1687399757000},"page":"2832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Contribution of Muscle Innate Immunity to Uremic Cachexia"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-5586","authenticated-orcid":false,"given":"Pasquale","family":"Esposito","sequence":"first","affiliation":[{"name":"Division of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"},{"name":"Department of Internal Medicine, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Verzola","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Saio","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Picciotto","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Frascio","sequence":"additional","affiliation":[{"name":"Division of Surgery, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"},{"name":"Department of Surgical Sciences and Integrated Diagnostics, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Laudon","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Ospedale Santa Chiara, 38122 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Zanetti","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"},{"name":"Department of Internal Medicine, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliano","family":"Brunori","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Ospedale Santa Chiara, 38122 Trento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6432-2429","authenticated-orcid":false,"given":"Giacomo","family":"Garibotto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4219-7043","authenticated-orcid":false,"given":"Francesca","family":"Viazzi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Dialysis and Transplantation, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"},{"name":"Department of Internal Medicine, University of Genova, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1053\/j.jrn.2018.08.006","article-title":"Global Prevalence of Protein-Energy Wasting in Kidney Disease: A Meta-analysis of Contemporary Observational Studies from the International Society of Renal Nutrition and Metabolism","volume":"28","author":"Carrero","year":"2018","journal-title":"J. Ren. Nutr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S83","DOI":"10.1681\/ASN.2004110972","article-title":"Inflammation markers, adhesion molecules, and all-cause and cardiovascular mortality in patients with ESRD: Searching for the best risk marker by multivariate modeling","volume":"16","author":"Tripepi","year":"2005","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.nut.2009.07.009","article-title":"Serum Protein and Mortality in Adults on Long-Term Hemodialysis: Exhaustive Review and Meta-Analysis","volume":"26","author":"Herselman","year":"2010","journal-title":"Nutrition"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1159\/000504240","article-title":"Practical Approach to Nutrition, Protein-Energy Wasting, Sarcopenia, and Cachexia in Patients with Chronic Kidney Disease","volume":"49","author":"Hanna","year":"2020","journal-title":"Blood Purif."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Price, S.R., Mitch, W.E., and Garibotto, G. (2022). Muscle Atrophy in CKD: A Historical Perspective of Advancements in Its Understanding. J. Ren. Nutr., S1051\u2013S2276.","DOI":"10.1053\/j.jrn.2022.09.009"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"318","DOI":"10.2215\/CJN.04470413","article-title":"Clinical Predictors of Decline in Nutritional Parameters over Time in ESRD","volume":"9","author":"Bots","year":"2014","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1546","DOI":"10.2215\/CJN.13121215","article-title":"Inflammation and progression of CKD: The CRIC Study","volume":"11","author":"Amdur","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1056\/NEJMoa041031","article-title":"Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization","volume":"351","author":"Go","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1056\/NEJM199704033361401","article-title":"Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men","volume":"336","author":"Ridker","year":"1997","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1046\/j.1523-1755.1999.00422.x","article-title":"Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure","volume":"55","author":"Stenvinkel","year":"1999","journal-title":"Kidney Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1111\/j.1525-139X.2005.00074.x","article-title":"Recent advances in understanding the malnutrition-inflammation-cachexia syndrome in chronic kidney disease patients: What is next?","volume":"18","year":"2005","journal-title":"Semin. Dial."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1001\/jamacardio.2021.3079","article-title":"Interleukin 6 and cardiovascular outcomes in patients with chronic kidney disease and chronic coronary syndrome","volume":"6","author":"Batra","year":"2021","journal-title":"JAMA Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.2215\/CJN.10441015","article-title":"Biomarkers of cardiovascular disease and mortality risk in patients with advanced CKD","volume":"11","author":"Sun","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1161\/CIRCULATIONAHA.121.053547","article-title":"Interleukin-1\u03b1 is a central regulator of leukocyte-endothelial adhesion in myocardial infarction and in chronic kidney disease","volume":"144","author":"Schunk","year":"2021","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.1093\/eurheartj\/ehac444","article-title":"Inflammation drives residual risk in chronic kidney disease: A CANTOS substudy","volume":"43","author":"Ridker","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1002\/jcsm.12459","article-title":"Signal regulatory protein alpha initiates cachexia through muscle to adipose tissue crosstalk","volume":"10","author":"Wu","year":"2019","journal-title":"J. Cachex.-Sarcopenia Muscle"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.cmet.2013.07.012","article-title":"Stat3 activation links a C\/EBP\u03b4 to myostatin pathway to stimulate loss of muscle mass","volume":"18","author":"Zhang","year":"2013","journal-title":"Cell Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/sj.ki.5001570","article-title":"Peripheral tissue release of interleukin-6 in patients with chronic kidney diseases: Effects of end-stage renal disease and microinflammatory state","volume":"70","author":"Garibotto","year":"2006","journal-title":"Kidney Int."},{"key":"ref_19","first-page":"e95185","article-title":"Systemic inflammation is associated with exaggerated skeletal muscle protein catabolism in maintenance hemodialysis patients","volume":"2","author":"Deger","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Torres, F.G., Molina, M., Soler-Majoral, J., Romero-Gonz\u00e1lez, G., Chitiva, N.R., Troya-Saborido, M., Rullan, G.S., Burgos, E., Mart\u00ednez, J.P., and Jou, M.U. (2022). Evolving Concepts on Inflammatory Biomarkers and Malnutrition in Chronic Kidney Disease. Nutrients, 14.","DOI":"10.3390\/nu14204297"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1523-1755.2005.00200.x","article-title":"IL-10, IL-6, and TNF-alpha: Central factors in the altered cytokine network of uremia--the good, the bad, and the ugly","volume":"67","author":"Stenvinkel","year":"2005","journal-title":"Kidney Int."},{"key":"ref_22","unstructured":"Gbd 2015 Mortality and Causes of Death Collaborators (2016). Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: A systematic analysis for the global burden of disease study 2015. Lancet, 388, 1459\u20131544."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.cyto.2007.02.015","article-title":"Kidney and splanchnic handling of interleukin-6 in humans","volume":"37","author":"Garibotto","year":"2007","journal-title":"Cytokine"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Dubuisson, N., Versele, R., Davis-L\u00f3pez de Carrizosa, M.A., Selvais, C.M., Brichard, S.M., and Abou-Samra, M. (2021). Walking down Skeletal Muscle Lane: From Inflammasome to Disease. Cells, 10.","DOI":"10.3390\/cells10113023"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1097\/SHK.0000000000002029","article-title":"Importance of the innate immune response in skeletal muscle to sepsis induced alterations in protein balance","volume":"59","author":"Lang","year":"2023","journal-title":"Shock"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrneph.2015.175","article-title":"Innate immunity in diabetes and diabetic nephropathy","volume":"12","author":"Wada","year":"2016","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Godkowicz, M., and Druszczy\u0144ska, M. (2022). NOD1,NOD2, and NLRC5 Receptors in Antiviral and Antimycobacterial Immunity. Vaccines, 10.","DOI":"10.3390\/vaccines10091487"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"E84","DOI":"10.2527\/jas.2007-0483","article-title":"Regulation of muscle growth by pathogen-associated molecules","volume":"86","author":"Frost","year":"2008","journal-title":"J. Anim. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"C706","DOI":"10.1152\/ajpcell.00626.2008","article-title":"Interleukin-1 stimulates catabolism in C2C12 myotubes","volume":"297","author":"Li","year":"2009","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1084\/jem.20111020","article-title":"Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis","volume":"208","author":"Braun","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"701386","DOI":"10.3389\/fnut.2021.701386","article-title":"How to overcome anabolic resistance in Dialysis-treated patients?","volume":"8","author":"Garibotto","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/s41467-020-20123-1","article-title":"Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease","volume":"12","author":"Sartori","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1002\/jcsm.12129","article-title":"Toll-like receptor 4 signalling mediates inflammation in skeletal muscle of patients with chronic kidney disease","volume":"8","author":"Verzola","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1038\/ki.2015.305","article-title":"Molecular Mechanisms of insulin resistance in chronic kidney disease","volume":"88","author":"Thomas","year":"2015","journal-title":"Kidney Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2230","DOI":"10.1016\/j.biocel.2013.06.027","article-title":"Muscle wasting from kidney failure-a model for catabolic conditions","volume":"45","author":"Wang","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4261","DOI":"10.4049\/jimmunol.1002013","article-title":"Viral inhibitory peptide of TLR4, a peptide derived from vaccinia protein A46 specifically inhibits TLR4 by directly targeting MyD88 adaptor-like and TRIF-related adaptor molecule","volume":"185","author":"Keogh","year":"2010","journal-title":"J. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1007\/s00109-004-0555-y","article-title":"Nuclear factor-kB: Its role in health and disease","volume":"82","author":"Kumar","year":"2004","journal-title":"J. Mol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1096\/fj.04-2364com","article-title":"TNF-\u03b1 acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1\/MAFbx in skeletal muscle","volume":"19","author":"Chen","year":"2005","journal-title":"FASEB J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1113\/jphysiol.2002.036673","article-title":"Mitogen-activated protein kinase [MAPK] pathway activation: Effects of age and acute exercise on human skeletal muscle","volume":"547","author":"Williamson","year":"2003","journal-title":"J. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1007\/s00125-003-1196-3","article-title":"Aberrant p38 mitogen-activated protein kinase signaling in skeletal muscle from Type 2 diabetic patients","volume":"46","author":"Koistinen","year":"2003","journal-title":"Diabetologia"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"C391","DOI":"10.1152\/ajpcell.00478.2002","article-title":"Temporal alterations in protein signaling cascades during recovery from muscle atrophy","volume":"285","author":"Childs","year":"2003","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/ana.10811","article-title":"Constitutive activation of MAPK cascade in acute quadriplegic myopathy","volume":"55","author":"Molon","year":"2004","journal-title":"Ann. Neurol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3048","DOI":"10.1002\/jcsm.13062","article-title":"The NLRP3 inflammasome contributes to inflammation-induced morphological and metabolic alterations in skeletal muscle","volume":"13","author":"Eggelbusch","year":"2022","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.cmet.2013.09.010","article-title":"Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging","volume":"18","author":"Youm","year":"2013","journal-title":"Cell Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40635-016-0115-0","article-title":"Deletion of Nlrp3 protects from inflammation-induced skeletal muscle atrophy","volume":"5","author":"Huang","year":"2017","journal-title":"Intensive Care Med. Exp."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Boursereau, R., Abou-Samra, M., Lecompte, S., Noel, L., and Brichard, S. (2018). Downregulation of the NLRP3 inflammasome by adiponectin rescues Duchenne muscular dystrophy. BMC Biol., 16.","DOI":"10.1186\/s12915-018-0501-z"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"514","DOI":"10.3892\/mmr.2021.12153","article-title":"NLRP3 inflammasome in sepsis","volume":"24","author":"Hi","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1161\/CIRCRESAHA.121.318908","article-title":"Deficient chaperone-mediated autophagy promotes inflammation and atherosclerosis","volume":"129","author":"Quiao","year":"2021","journal-title":"Circ. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"F938","DOI":"10.1152\/ajprenal.00256.2017","article-title":"Inflammation and premature aging in advanced chronic kidney disease","volume":"313","author":"Kooman","year":"2017","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1002\/rco2.75","article-title":"A Toll-like receptor-4\/NLRP3 inflammasome pathway promotes inflammation in skeletal muscle of chronic kidney disease patients","volume":"6","author":"Verzola","year":"2023","journal-title":"JCSM Rapid Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1053\/j.jrn.2023.01.007","article-title":"Association of Diet-dependent Systemic Acid Load, Renal Function, and Serum Albumin Concentration","volume":"3","author":"Banerjee","year":"2023","journal-title":"J. Ren. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1007\/s40620-020-00955-2","article-title":"Protein-bound uremic toxin lowering strategies in chronic kidney disease: A systematic review and metaanalysis","volume":"34","author":"Takkavatakarn","year":"2021","journal-title":"J. Nephrol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Avin, K.G., Chen, N.X., Organ, J.M., Zarse, C., O\u2019Neill, K., Conway, R.G., Konrad, R.J., Bacallao, R.L., Allen, M.R., and Moe, S.M. (2016). Skeletal muscle regeneration and oxidative stress are altered in chronic kidney disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159411"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e139826","DOI":"10.1172\/jci.insight.139826","article-title":"Impaired muscle mitochondrial energetics is associated with uremic metabolite accumulation in chronic kidney disease","volume":"6","author":"Thome","year":"2021","journal-title":"JCI Insight"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Adesso, S., Popolo, A., Bianco, G., Sorrentino, R., Pinto, A., Autore, G., and Marzocco, S. (2013). The Uremic Toxin Indoxyl Sulphate Enhances Macrophage Response to LPS. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076778"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3155","DOI":"10.3390\/toxins7083155","article-title":"Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate","volume":"7","author":"Matsuo","year":"2015","journal-title":"Toxins"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s12012-021-09718-2","article-title":"Indoxyl Sulfate Activates NLRP3 Inflammasome to Induce Cardiac Contractile Dysfunction Accompanied by Myocardial Fibrosis and Hypertrophy","volume":"22","author":"Yamaguchi","year":"2022","journal-title":"Cardiovasc. Toxicol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E150","DOI":"10.1152\/ajpendo.00161.2020","article-title":"Myostatin deficiency not only prevents muscle wasting but also improves survival in septic mice","volume":"320","author":"Kobayashi","year":"2021","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.kint.2018.10.010","article-title":"Emerging role of myostatin and its inhibition in the setting of chronic kidney disease","volume":"95","author":"Verzola","year":"2019","journal-title":"Kidney Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41581-021-00498-0","article-title":"Pathophysiological mechanisms leading to muscle loss in chronic kidney disease","volume":"18","author":"Wang","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/jcsm.13112","article-title":"The impact of senescence on muscle wasting in chronic kidney disease","volume":"14","author":"Huang","year":"2023","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1681\/ASN.2018121251","article-title":"Cellular Senescence in the Kidney","volume":"30","author":"Docherty","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.jbspin.2018.08.001","article-title":"Sarcopenia","volume":"86","author":"Tournadre","year":"2019","journal-title":"Jt. Bone Spine"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1152\/physrev.00061.2017","article-title":"Sarcopenia: Aging-Related Loss of Muscle Mass and Function","volume":"99","author":"Larsson","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1093\/jn\/nxaa002","article-title":"Mediterranean Diet Increases Endothelial Function in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"150","author":"Shannon","year":"2020","journal-title":"J. Nutr."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.3390\/nu15071767","article-title":"Role of Hydroxytyrosol and Oleuropein in the Prevention of Aging and Related Disorders: Focus on Neurodegeneration, Skeletal Muscle Dysfunction and Gut Microbiota","volume":"15","author":"Micheli","year":"2023","journal-title":"Nutrients"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.2215\/CJN.12691117","article-title":"Microbiome and cardiovascular disease in CKD","volume":"13","author":"Jovanovich","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1681\/ASN.2013080905","article-title":"The gut microbiome, kidney disease, and targeted interventions","volume":"25","author":"Ramezani","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1681\/ASN.2014010042","article-title":"Randomized placebo-controlled EPPIC trials of AST-120 in CKD","volume":"26","author":"Schulman","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/oby.20072","article-title":"Effect of dietary composition of weight loss diets on high-sensitivity C-reactive protein: The randomized POUNDS LOST trial","volume":"21","author":"Nicklas","year":"2013","journal-title":"Obesity"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2181","DOI":"10.1016\/j.jacc.2020.09.535","article-title":"Dietary inflammatory potential and risk of cardiovascular disease among men and women in the US","volume":"76","author":"Li","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1056\/NEJMoa1800389","article-title":"Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts","volume":"378","author":"Estruch","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1053\/j.ajkd.2009.09.025","article-title":"Effect of intradialytic versus home-based aerobic exercise training on physical function and vascular parameters in hemodialysis patients: A randomized pilot study","volume":"55","author":"Koh","year":"2010","journal-title":"Am. J. Kidney Dis."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1053\/j.ajkd.2009.03.009","article-title":"Effects of exercise training on noninvasive cardiac measures in patients undergoing long-term hemodialysis: A randomized controlled trial","volume":"54","author":"Kouidi","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1038\/s41581-022-00675-9","article-title":"Exercise and chronic kidney disease: Potential mechanisms underlying the physiological benefits","volume":"19","author":"Bishop","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1080\/02640414.2015.1017733","article-title":"The BASES expert statement on exercise therapy for people with chronic kidney disease","volume":"33","author":"Koufaki","year":"2015","journal-title":"J. Sport. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.jsams.2013.01.005","article-title":"Exercise & Sports Science Australia [ESSA] position statement on exercise and chronic kidney disease","volume":"16","author":"Smart","year":"2013","journal-title":"J. Sci. Med. Sport"},{"key":"ref_78","unstructured":"K\/DOQI Workgroup (2012). K\/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am. J. Kidney Dis., 45, S1\u2013S153."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.ekir.2017.06.008","article-title":"Exercise training in elderly people undergoing hemodialysis: A systematic review and meta-analysis","volume":"2","author":"Matsuzawa","year":"2017","journal-title":"Kidney Int. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.ekir.2020.12.001","article-title":"An international delphi survey on exercise priorities in CKD","volume":"6","author":"Labib","year":"2020","journal-title":"Kidney Int. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.stem.2016.11.020","article-title":"Injury-Induced Senescence Enables In Vivo Reprogramming in Skeletal Muscle","volume":"20","author":"Chiche","year":"2017","journal-title":"Cell Stem Cell"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"747","DOI":"10.18632\/aging.101425","article-title":"Oxidative stress-mediated senescence in mesenchymal progenitor cells causes the loss of their fibro\/adipogenic potential and abrogates myoblast fusion","volume":"10","author":"Sugihara","year":"2018","journal-title":"Aging"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1016\/j.xkme.2021.07.010","article-title":"Marine n-3 Polyunsaturated Fatty Acids and Cellular Senescence Markers in Incident Kidney Transplant Recipients: The Omega-3 Fatty Acids in Renal Transplantation [ORENTRA] Randomized Clinical Trial","volume":"3","author":"Chan","year":"2021","journal-title":"Kidney Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.csbj.2019.06.019","article-title":"Computational Drug Screening Identifies Compounds Targeting Renal Age-associated Molecular Profiles","volume":"17","author":"Koppelstaetter","year":"2019","journal-title":"Comput. Struct Biotechnol. J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e141848","DOI":"10.1172\/JCI141848","article-title":"Age-related GSK3\u03b2 overexpression drives podocyte senescence and glomerular aging","volume":"132","author":"Fang","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1111\/dom.14503","article-title":"Sodium-glucose cotransporter-2 inhibition reduces cellular senescence in the diabetic kidney by promoting ketone body-induced NRF2 activation","volume":"23","author":"Kim","year":"2021","journal-title":"Diabetes Obes. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"955","DOI":"10.18632\/aging.101202","article-title":"New agents that target senescent cells: The flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463","volume":"9","author":"Zhu","year":"2017","journal-title":"Aging"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"17784","DOI":"10.1074\/jbc.M115.655019","article-title":"Sulforaphane Attenuates Muscle Inflammation in Dystrophin-deficient mdx Mice via NF-E2-related Factor 2 [Nrf2]-mediated Inhibition of NF-\u03baB Signaling Pathway","volume":"290","author":"Sun","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.lfs.2019.05.056","article-title":"Activation of cannabinoid type 2 receptor protects skeletal muscle from ischemia-reperfusion injury partly via Nrf2 signaling","volume":"230","author":"Zhang","year":"2019","journal-title":"Life Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"F1122","DOI":"10.1152\/ajprenal.00202.2019","article-title":"Reduced skeletal muscle expression of mitochondrial-derived peptides humanin and MOTS-C and Nrf2 in chronic kidney disease","volume":"317","author":"Liu","year":"2019","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1056\/NEJMoa1105351","article-title":"BEAM Study Investigators. Bardoxolone methyl and kidney function in CKD with type 2 diabetes","volume":"365","author":"Pergola","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1056\/NEJMoa1306033","article-title":"BEACON Trial Investigators. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease","volume":"369","author":"Akizawa","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/s41581-022-00621-9","article-title":"Targeting innate immunity-driven inflammation in CKD and cardiovascular disease","volume":"18","author":"Speer","year":"2022","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1189\/jlb.3HI0715-321R","article-title":"The Inflammasome NLRP3 Plays a Protective Role against a Viral Immunopathological Lesion","volume":"99","author":"Gimenez","year":"2016","journal-title":"J. Leukoc. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"108053","DOI":"10.1016\/j.pharmthera.2021.108053","article-title":"Targeting the NLRP3 inflammasome in cardiovascular diseases","volume":"236","author":"Toldo","year":"2022","journal-title":"Pharmacol. Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12621","article-title":"Overview of the IL-1 family in innate inflammation and acquired immunity","volume":"281","author":"Dinarello","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Benny Klimek, M.E., Sali, A., Rayavarapu, S., Van der Meulen, J.H., and Nagaraju, K. (2016). Effect of the IL-1 receptor antagonist Kineret[R] on disease phenotype in mdx mice. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155944"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1681\/ASN.2010070760","article-title":"IL-1beta receptor antagonist reduces inflammation in hemodialysis patients","volume":"22","author":"Hung","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1016\/j.kint.2022.06.022","article-title":"Hemodialysis Novel Therapies Consortium. A randomized controlled pilot trial of anakinra for hemodialysis inflammation","volume":"102","author":"Dember","year":"2022","journal-title":"Kidney Int."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"15141","DOI":"10.1038\/s41598-021-94565-y","article-title":"The role of IL-1 in adipose browning and muscle wasting in CKD-associated cachexia","volume":"11","author":"Cheung","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1124\/mol.110.068064","article-title":"TAK-242 [resatorvid], a small-molecule inhibitor of Toll-like receptor [TLR] 4 signaling, binds selectively t TLR4 and interferes with interactions betwee TLR4 and its adaptor molecules","volume":"79","author":"Matsunaga","year":"2011","journal-title":"Mol. Pharmacol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1038\/s41598-020-57714-3","article-title":"TAK-242, aspecific inhibitor of Toll-like receptor 4 signalling, prevents endotoxemia-inducedskeletal muscle wasting in mice","volume":"10","author":"Ono","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1097\/CCM.0b013e3181e7c5c9","article-title":"A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis","volume":"38","author":"Rice","year":"2010","journal-title":"Crit. Care Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/13\/2832\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:58:05Z","timestamp":1760126285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/13\/2832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,21]]},"references-count":103,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["nu15132832"],"URL":"https:\/\/doi.org\/10.3390\/nu15132832","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,21]]}}}