Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease
Mitochondria abnormalities in skeletal muscle may contribute to frailty and sarcopenia, commonly present in patients with chronic kidney disease (CKD). Dysfunctional mitochondria are also a major source of oxidative stress and may contribute to cardiovascular disease in CKD. We tested the hypothesis...
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| creator | Gamboa, Jorge L. Billings, Frederic T. Bojanowski, Matthew T. Gilliam, Laura A. Yu, Chang Roshanravan, Baback Roberts, L. Jackson Himmelfarb, Jonathan Ikizler, T. Alp Brown, Nancy J. |
| description | Mitochondria abnormalities in skeletal muscle may contribute to frailty and sarcopenia, commonly present in patients with chronic kidney disease (CKD). Dysfunctional mitochondria are also a major source of oxidative stress and may contribute to cardiovascular disease in CKD. We tested the hypothesis that mitochondrial structure and function worsens with the severity of CKD. Mitochondrial volume density, mitochondrial DNA (mtDNA) copy number, BNIP3, and PGC1α protein expression were evaluated in skeletal muscle biopsies obtained from 27 subjects (17 controls and 10 with CKD stage 5 on hemodialysis). We also measured mtDNA copy number in peripheral blood mononuclear cells (PBMCs), plasma isofurans, and plasma F2‐isoprostanes in 208 subjects divided into three groups: non‐CKD (eGFR>60 mL/min), CKD stage 3–4 (eGFR 60–15 mL/min), and CKD stage 5 (on hemodialysis). Muscle biopsies from patients with CKD stage 5 revealed lower mitochondrial volume density, lower mtDNA copy number, and higher BNIP3 content than controls. mtDNA copy number in PBMCs was decreased with increasing severity of CKD: non‐CKD (6.48, 95% CI 4.49–8.46), CKD stage 3–4 (3.30, 95% CI 0.85–5.75, P = 0.048 vs. non‐CKD), and CKD stage 5 (1.93, 95% CI 0.27–3.59, P = 0.001 vs. non‐CKD). Isofurans were higher in patients with CKD stage 5 (median 59.21 pg/mL, IQR 41.76–95.36) compared to patients with non‐CKD (median 49.95 pg/mL, IQR 27.88–83.46, P = 0.001), whereas F2‐isoprostanes did not differ among groups. Severity of CKD is associated with mitochondrial dysfunction and markers of oxidative stress. Mitochondrial abnormalities, which are common in skeletal muscle from patients with CKD stage 5, may explain the muscle dysfunction associated with frailty and sarcopenia in CKD. Further studies are required to evaluate mitochondrial function in vivo in patients with different CKD stages.
We present data showing for the very first time that the number of mitochondria is diminished in skeletal muscle biopsies from patients on maintenance hemodialysis. We also confirmed the presence of ultrastructure abnormalities in skeletal muscle mitochondria in patients on hemodialysis. We also found that markers of mitochondrial dysfunction are commonly present in patients with chronic kidney disease, and these markers can be detected in blood samples. |
| doi_str_mv | 10.14814/phy2.12780 |
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We present data showing for the very first time that the number of mitochondria is diminished in skeletal muscle biopsies from patients on maintenance hemodialysis. We also confirmed the presence of ultrastructure abnormalities in skeletal muscle mitochondria in patients on hemodialysis. We also found that markers of mitochondrial dysfunction are commonly present in patients with chronic kidney disease, and these markers can be detected in blood samples.</description><identifier>ISSN: 2051-817X</identifier><identifier>EISSN: 2051-817X</identifier><identifier>DOI: 10.14814/phy2.12780</identifier><identifier>PMID: 27162261</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>Adult ; Animals ; Biomarkers ; Biopsy ; Blood pressure ; BNIP3 ; BNIP3 protein ; Cardiovascular diseases ; chronic kidney disease ; Copy number ; Deoxyribonucleic acid ; DNA ; Epidermal growth factor receptors ; Female ; Frailty ; Heart surgery ; Hemodialysis ; Humans ; Hypotheses ; Isoprostanes ; Kidney diseases ; Leukocytes (mononuclear) ; Male ; Mice ; Mice, Inbred C57BL ; Microscopy ; Middle Aged ; Mitochondria ; Mitochondria - metabolism ; Mitochondria - pathology ; Mitochondrial DNA ; mitochondrial DNA copy number ; Morbidity ; Mortality ; Muscle, Skeletal - metabolism ; Muscle, Skeletal - pathology ; Muscular Conditions, Disorders and Treatments ; Musculoskeletal system ; Original Research ; Oxidative stress ; Oxidative Stress - physiology ; Peripheral blood mononuclear cells ; PGC1α ; Physiology ; Renal Conditions, Disorders and Treatments ; Renal Insufficiency, Chronic - diagnosis ; Renal Insufficiency, Chronic - metabolism ; Renal Insufficiency, Chronic - pathology ; Sarcopenia ; Skeletal Muscle ; Structure-function relationships ; Studies</subject><ispartof>Physiological reports, 2016-05, Vol.4 (9), p.e12780-n/a</ispartof><rights>2016 The Authors. published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.</rights><rights>2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.</rights><rights>2016. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5130-15bc36180e88392027bb2765aaff33e2454a2cd68912aa9225a57cd9decd0f93</citedby><cites>FETCH-LOGICAL-c5130-15bc36180e88392027bb2765aaff33e2454a2cd68912aa9225a57cd9decd0f93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873632/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4873632/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27162261$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gamboa, Jorge L.</creatorcontrib><creatorcontrib>Billings, Frederic T.</creatorcontrib><creatorcontrib>Bojanowski, Matthew T.</creatorcontrib><creatorcontrib>Gilliam, Laura A.</creatorcontrib><creatorcontrib>Yu, Chang</creatorcontrib><creatorcontrib>Roshanravan, Baback</creatorcontrib><creatorcontrib>Roberts, L. Jackson</creatorcontrib><creatorcontrib>Himmelfarb, Jonathan</creatorcontrib><creatorcontrib>Ikizler, T. Alp</creatorcontrib><creatorcontrib>Brown, Nancy J.</creatorcontrib><title>Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease</title><title>Physiological reports</title><addtitle>Physiol Rep</addtitle><description>Mitochondria abnormalities in skeletal muscle may contribute to frailty and sarcopenia, commonly present in patients with chronic kidney disease (CKD). Dysfunctional mitochondria are also a major source of oxidative stress and may contribute to cardiovascular disease in CKD. We tested the hypothesis that mitochondrial structure and function worsens with the severity of CKD. Mitochondrial volume density, mitochondrial DNA (mtDNA) copy number, BNIP3, and PGC1α protein expression were evaluated in skeletal muscle biopsies obtained from 27 subjects (17 controls and 10 with CKD stage 5 on hemodialysis). We also measured mtDNA copy number in peripheral blood mononuclear cells (PBMCs), plasma isofurans, and plasma F2‐isoprostanes in 208 subjects divided into three groups: non‐CKD (eGFR>60 mL/min), CKD stage 3–4 (eGFR 60–15 mL/min), and CKD stage 5 (on hemodialysis). Muscle biopsies from patients with CKD stage 5 revealed lower mitochondrial volume density, lower mtDNA copy number, and higher BNIP3 content than controls. mtDNA copy number in PBMCs was decreased with increasing severity of CKD: non‐CKD (6.48, 95% CI 4.49–8.46), CKD stage 3–4 (3.30, 95% CI 0.85–5.75, P = 0.048 vs. non‐CKD), and CKD stage 5 (1.93, 95% CI 0.27–3.59, P = 0.001 vs. non‐CKD). Isofurans were higher in patients with CKD stage 5 (median 59.21 pg/mL, IQR 41.76–95.36) compared to patients with non‐CKD (median 49.95 pg/mL, IQR 27.88–83.46, P = 0.001), whereas F2‐isoprostanes did not differ among groups. Severity of CKD is associated with mitochondrial dysfunction and markers of oxidative stress. Mitochondrial abnormalities, which are common in skeletal muscle from patients with CKD stage 5, may explain the muscle dysfunction associated with frailty and sarcopenia in CKD. Further studies are required to evaluate mitochondrial function in vivo in patients with different CKD stages.
We present data showing for the very first time that the number of mitochondria is diminished in skeletal muscle biopsies from patients on maintenance hemodialysis. We also confirmed the presence of ultrastructure abnormalities in skeletal muscle mitochondria in patients on hemodialysis. We also found that markers of mitochondrial dysfunction are commonly present in patients with chronic kidney disease, and these markers can be detected in blood samples.</description><subject>Adult</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Blood pressure</subject><subject>BNIP3</subject><subject>BNIP3 protein</subject><subject>Cardiovascular diseases</subject><subject>chronic kidney disease</subject><subject>Copy number</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Epidermal growth factor receptors</subject><subject>Female</subject><subject>Frailty</subject><subject>Heart surgery</subject><subject>Hemodialysis</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Isoprostanes</subject><subject>Kidney diseases</subject><subject>Leukocytes (mononuclear)</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy</subject><subject>Middle Aged</subject><subject>Mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondria - pathology</subject><subject>Mitochondrial DNA</subject><subject>mitochondrial DNA copy number</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscle, Skeletal - pathology</subject><subject>Muscular Conditions, Disorders and Treatments</subject><subject>Musculoskeletal system</subject><subject>Original Research</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - physiology</subject><subject>Peripheral blood mononuclear cells</subject><subject>PGC1α</subject><subject>Physiology</subject><subject>Renal Conditions, Disorders and Treatments</subject><subject>Renal Insufficiency, Chronic - diagnosis</subject><subject>Renal Insufficiency, Chronic - metabolism</subject><subject>Renal Insufficiency, Chronic - pathology</subject><subject>Sarcopenia</subject><subject>Skeletal Muscle</subject><subject>Structure-function relationships</subject><subject>Studies</subject><issn>2051-817X</issn><issn>2051-817X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqFkUFLHTEURkNpUbGu3JdAN4XybHIzySSbQpGqBUtdSKmrkJdkOrHzktdkRp1_b-pTsV3UVUJyOHz3fgjtU3JAG0mbD-t-hgMKrSQv0A4QTheStj9ePrlvo71SLgkhlDCmSLOFtqGlAkDQHfT9axiT7VN0OZgBu7l0U7RjSBGb6HC6Cc6M4crjMmZfCg4Rr-uDj2PB12Hsse1zisHiX8FFP2MXijfFv0avOjMUv3d_7qLzo8_nhyeL02_HXw4_nS4sp4wsKF9aJqgkXkqmgEC7XEIruDFdx5iHhjcGrBNSUTBGAXDDW-uU89aRTrFd9HGjXU_LlXe2xspm0OscVibPOpmg__6Jodc_05VuZMsEgyp4dy_I6ffky6hXoVg_DCb6NBVdo0nRUMHV82grZd0pB1bRt_-gl2nKsS5CAyjCBQhFK_V-Q9mcSsm-e8xNib4rV_8pV9-VW-k3T0d9ZB-qrABsgOsw-Pl_Ln12cgEb6y0lq6__</recordid><startdate>201605</startdate><enddate>201605</enddate><creator>Gamboa, Jorge L.</creator><creator>Billings, Frederic T.</creator><creator>Bojanowski, Matthew T.</creator><creator>Gilliam, Laura A.</creator><creator>Yu, Chang</creator><creator>Roshanravan, Baback</creator><creator>Roberts, L. 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Jackson ; Himmelfarb, Jonathan ; Ikizler, T. Alp ; Brown, Nancy J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5130-15bc36180e88392027bb2765aaff33e2454a2cd68912aa9225a57cd9decd0f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Biopsy</topic><topic>Blood pressure</topic><topic>BNIP3</topic><topic>BNIP3 protein</topic><topic>Cardiovascular diseases</topic><topic>chronic kidney disease</topic><topic>Copy number</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Epidermal growth factor receptors</topic><topic>Female</topic><topic>Frailty</topic><topic>Heart surgery</topic><topic>Hemodialysis</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Isoprostanes</topic><topic>Kidney diseases</topic><topic>Leukocytes (mononuclear)</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy</topic><topic>Middle Aged</topic><topic>Mitochondria</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondria - pathology</topic><topic>Mitochondrial DNA</topic><topic>mitochondrial DNA copy number</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscle, Skeletal - pathology</topic><topic>Muscular Conditions, Disorders and Treatments</topic><topic>Musculoskeletal system</topic><topic>Original Research</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - physiology</topic><topic>Peripheral blood mononuclear cells</topic><topic>PGC1α</topic><topic>Physiology</topic><topic>Renal Conditions, Disorders and Treatments</topic><topic>Renal Insufficiency, Chronic - diagnosis</topic><topic>Renal Insufficiency, Chronic - metabolism</topic><topic>Renal Insufficiency, Chronic - pathology</topic><topic>Sarcopenia</topic><topic>Skeletal Muscle</topic><topic>Structure-function relationships</topic><topic>Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gamboa, Jorge L.</creatorcontrib><creatorcontrib>Billings, Frederic T.</creatorcontrib><creatorcontrib>Bojanowski, Matthew T.</creatorcontrib><creatorcontrib>Gilliam, Laura A.</creatorcontrib><creatorcontrib>Yu, Chang</creatorcontrib><creatorcontrib>Roshanravan, Baback</creatorcontrib><creatorcontrib>Roberts, L. 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Jackson</au><au>Himmelfarb, Jonathan</au><au>Ikizler, T. Alp</au><au>Brown, Nancy J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease</atitle><jtitle>Physiological reports</jtitle><addtitle>Physiol Rep</addtitle><date>2016-05</date><risdate>2016</risdate><volume>4</volume><issue>9</issue><spage>e12780</spage><epage>n/a</epage><pages>e12780-n/a</pages><issn>2051-817X</issn><eissn>2051-817X</eissn><abstract>Mitochondria abnormalities in skeletal muscle may contribute to frailty and sarcopenia, commonly present in patients with chronic kidney disease (CKD). Dysfunctional mitochondria are also a major source of oxidative stress and may contribute to cardiovascular disease in CKD. We tested the hypothesis that mitochondrial structure and function worsens with the severity of CKD. Mitochondrial volume density, mitochondrial DNA (mtDNA) copy number, BNIP3, and PGC1α protein expression were evaluated in skeletal muscle biopsies obtained from 27 subjects (17 controls and 10 with CKD stage 5 on hemodialysis). We also measured mtDNA copy number in peripheral blood mononuclear cells (PBMCs), plasma isofurans, and plasma F2‐isoprostanes in 208 subjects divided into three groups: non‐CKD (eGFR>60 mL/min), CKD stage 3–4 (eGFR 60–15 mL/min), and CKD stage 5 (on hemodialysis). Muscle biopsies from patients with CKD stage 5 revealed lower mitochondrial volume density, lower mtDNA copy number, and higher BNIP3 content than controls. mtDNA copy number in PBMCs was decreased with increasing severity of CKD: non‐CKD (6.48, 95% CI 4.49–8.46), CKD stage 3–4 (3.30, 95% CI 0.85–5.75, P = 0.048 vs. non‐CKD), and CKD stage 5 (1.93, 95% CI 0.27–3.59, P = 0.001 vs. non‐CKD). Isofurans were higher in patients with CKD stage 5 (median 59.21 pg/mL, IQR 41.76–95.36) compared to patients with non‐CKD (median 49.95 pg/mL, IQR 27.88–83.46, P = 0.001), whereas F2‐isoprostanes did not differ among groups. Severity of CKD is associated with mitochondrial dysfunction and markers of oxidative stress. Mitochondrial abnormalities, which are common in skeletal muscle from patients with CKD stage 5, may explain the muscle dysfunction associated with frailty and sarcopenia in CKD. Further studies are required to evaluate mitochondrial function in vivo in patients with different CKD stages.
We present data showing for the very first time that the number of mitochondria is diminished in skeletal muscle biopsies from patients on maintenance hemodialysis. We also confirmed the presence of ultrastructure abnormalities in skeletal muscle mitochondria in patients on hemodialysis. We also found that markers of mitochondrial dysfunction are commonly present in patients with chronic kidney disease, and these markers can be detected in blood samples.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>27162261</pmid><doi>10.14814/phy2.12780</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Animals Biomarkers Biopsy Blood pressure BNIP3 BNIP3 protein Cardiovascular diseases chronic kidney disease Copy number Deoxyribonucleic acid DNA Epidermal growth factor receptors Female Frailty Heart surgery Hemodialysis Humans Hypotheses Isoprostanes Kidney diseases Leukocytes (mononuclear) Male Mice Mice, Inbred C57BL Microscopy Middle Aged Mitochondria Mitochondria - metabolism Mitochondria - pathology Mitochondrial DNA mitochondrial DNA copy number Morbidity Mortality Muscle, Skeletal - metabolism Muscle, Skeletal - pathology Muscular Conditions, Disorders and Treatments Musculoskeletal system Original Research Oxidative stress Oxidative Stress - physiology Peripheral blood mononuclear cells PGC1α Physiology Renal Conditions, Disorders and Treatments Renal Insufficiency, Chronic - diagnosis Renal Insufficiency, Chronic - metabolism Renal Insufficiency, Chronic - pathology Sarcopenia Skeletal Muscle Structure-function relationships Studies |
| title | Mitochondrial dysfunction and oxidative stress in patients with chronic kidney disease |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T01%3A25%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mitochondrial%20dysfunction%20and%20oxidative%20stress%20in%20patients%20with%20chronic%20kidney%20disease&rft.jtitle=Physiological%20reports&rft.au=Gamboa,%20Jorge%20L.&rft.date=2016-05&rft.volume=4&rft.issue=9&rft.spage=e12780&rft.epage=n/a&rft.pages=e12780-n/a&rft.issn=2051-817X&rft.eissn=2051-817X&rft_id=info:doi/10.14814/phy2.12780&rft_dat=%3Cproquest_pubme%3E1788226523%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2290562691&rft_id=info:pmid/27162261&rfr_iscdi=true |