Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure
One-quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI)-an abrupt reduction or loss of kidney function associated with increased long-term mortality. There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date,...
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| Veröffentlicht in: | International journal of molecular sciences 2022-01, Vol.23 (2), p.1009 |
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| creator | Templeton, Evelyn M Lassé, Moritz Kleffmann, Torsten Ellmers, Leigh J Palmer, Suetonia C Davidson, Trent Scott, Nicola J A Pickering, John W Charles, Christopher J Endre, Zoltan H Cameron, Vicky A Richards, A Mark Rademaker, Miriam T Pilbrow, Anna P |
| description | One-quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI)-an abrupt reduction or loss of kidney function associated with increased long-term mortality. There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date, no protein biomarkers have exhibited sufficient diagnostic or prognostic performance for widespread clinical uptake. We aimed to identify novel protein biomarkers of AKI associated with ADHF by quantifying changes in protein abundance in the kidneys that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using sequential window acquisition of all theoretical fragment ion spectra-mass spectrometry (SWATH-MS) in kidney cortices from control sheep (
= 5), sheep with established rapid-pacing-induced ADHF (
= 8), and sheep after ~4 weeks recovery from ADHF (
= 7). Of the 790 proteins quantified, we identified 17 candidate kidney injury markers in ADHF, 1 potential kidney marker of ADHF recovery, and 2 potential markers of long-term renal impairment (differential abundance between groups of 1.2-2.6-fold, adjusted
< 0.05). Among these 20 candidate protein markers of kidney injury were 6 candidates supported by existing evidence and 14 novel candidates not previously implicated in AKI. Proteins of differential abundance were enriched in pro-inflammatory signalling pathways: glycoprotein VI (activated during ADHF development; adjusted
< 0.01) and acute phase response (repressed during recovery from ADHF; adjusted
< 0.01). New biomarkers for the early detection of AKI in ADHF may help us to evaluate effective treatment strategies to prevent mortality and improve outcomes for patients. |
| doi_str_mv | 10.3390/ijms23021009 |
| format | Article |
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= 5), sheep with established rapid-pacing-induced ADHF (
= 8), and sheep after ~4 weeks recovery from ADHF (
= 7). Of the 790 proteins quantified, we identified 17 candidate kidney injury markers in ADHF, 1 potential kidney marker of ADHF recovery, and 2 potential markers of long-term renal impairment (differential abundance between groups of 1.2-2.6-fold, adjusted
< 0.05). Among these 20 candidate protein markers of kidney injury were 6 candidates supported by existing evidence and 14 novel candidates not previously implicated in AKI. Proteins of differential abundance were enriched in pro-inflammatory signalling pathways: glycoprotein VI (activated during ADHF development; adjusted
< 0.01) and acute phase response (repressed during recovery from ADHF; adjusted
< 0.01). New biomarkers for the early detection of AKI in ADHF may help us to evaluate effective treatment strategies to prevent mortality and improve outcomes for patients.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms23021009</identifier><identifier>PMID: 35055195</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acute Kidney Injury - blood ; Acute Kidney Injury - diagnosis ; Acute Kidney Injury - metabolism ; Acute Kidney Injury - urine ; Animals ; Biomarkers ; Biomarkers - blood ; Biomarkers - metabolism ; Biomarkers - urine ; Candidates ; Congestive heart failure ; Creatinine ; Disease Models, Animal ; FDA approval ; Glycoprotein VI ; Heart failure ; Heart Failure - blood ; Heart Failure - complications ; Heart Failure - metabolism ; Heart Failure - urine ; Humans ; Inflammation ; Injury prevention ; Kidneys ; Kinases ; Mass spectrometry ; Mass spectroscopy ; Mortality ; Patients ; Physiology ; Plasma ; Platelet Membrane Glycoproteins - metabolism ; Platelet Membrane Glycoproteins - urine ; Prognosis ; Protein folding ; Proteins ; Proteomics - methods ; Renal failure ; Sheep ; Signal transduction</subject><ispartof>International journal of molecular sciences, 2022-01, Vol.23 (2), p.1009</ispartof><rights>2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c369t-e163a965c071ba202cc8b3a9fbb9019e1dcd5109511270796ba4b00622e17a723</cites><orcidid>0000-0001-5735-9549 ; 0000-0002-5767-794X ; 0000-0003-3147-683X ; 0000-0002-5685-9151 ; 0000-0001-9807-8022</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778509/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8778509/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35055195$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Templeton, Evelyn M</creatorcontrib><creatorcontrib>Lassé, Moritz</creatorcontrib><creatorcontrib>Kleffmann, Torsten</creatorcontrib><creatorcontrib>Ellmers, Leigh J</creatorcontrib><creatorcontrib>Palmer, Suetonia C</creatorcontrib><creatorcontrib>Davidson, Trent</creatorcontrib><creatorcontrib>Scott, Nicola J A</creatorcontrib><creatorcontrib>Pickering, John W</creatorcontrib><creatorcontrib>Charles, Christopher J</creatorcontrib><creatorcontrib>Endre, Zoltan H</creatorcontrib><creatorcontrib>Cameron, Vicky A</creatorcontrib><creatorcontrib>Richards, A Mark</creatorcontrib><creatorcontrib>Rademaker, Miriam T</creatorcontrib><creatorcontrib>Pilbrow, Anna P</creatorcontrib><title>Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>One-quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI)-an abrupt reduction or loss of kidney function associated with increased long-term mortality. There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date, no protein biomarkers have exhibited sufficient diagnostic or prognostic performance for widespread clinical uptake. We aimed to identify novel protein biomarkers of AKI associated with ADHF by quantifying changes in protein abundance in the kidneys that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using sequential window acquisition of all theoretical fragment ion spectra-mass spectrometry (SWATH-MS) in kidney cortices from control sheep (
= 5), sheep with established rapid-pacing-induced ADHF (
= 8), and sheep after ~4 weeks recovery from ADHF (
= 7). Of the 790 proteins quantified, we identified 17 candidate kidney injury markers in ADHF, 1 potential kidney marker of ADHF recovery, and 2 potential markers of long-term renal impairment (differential abundance between groups of 1.2-2.6-fold, adjusted
< 0.05). Among these 20 candidate protein markers of kidney injury were 6 candidates supported by existing evidence and 14 novel candidates not previously implicated in AKI. Proteins of differential abundance were enriched in pro-inflammatory signalling pathways: glycoprotein VI (activated during ADHF development; adjusted
< 0.01) and acute phase response (repressed during recovery from ADHF; adjusted
< 0.01). New biomarkers for the early detection of AKI in ADHF may help us to evaluate effective treatment strategies to prevent mortality and improve outcomes for patients.</description><subject>Acute Kidney Injury - blood</subject><subject>Acute Kidney Injury - diagnosis</subject><subject>Acute Kidney Injury - metabolism</subject><subject>Acute Kidney Injury - urine</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Biomarkers - metabolism</subject><subject>Biomarkers - urine</subject><subject>Candidates</subject><subject>Congestive heart failure</subject><subject>Creatinine</subject><subject>Disease Models, Animal</subject><subject>FDA approval</subject><subject>Glycoprotein VI</subject><subject>Heart failure</subject><subject>Heart Failure - blood</subject><subject>Heart Failure - complications</subject><subject>Heart Failure - metabolism</subject><subject>Heart Failure - urine</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Injury prevention</subject><subject>Kidneys</subject><subject>Kinases</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Mortality</subject><subject>Patients</subject><subject>Physiology</subject><subject>Plasma</subject><subject>Platelet Membrane Glycoproteins - metabolism</subject><subject>Platelet Membrane Glycoproteins - urine</subject><subject>Prognosis</subject><subject>Protein folding</subject><subject>Proteins</subject><subject>Proteomics - methods</subject><subject>Renal failure</subject><subject>Sheep</subject><subject>Signal transduction</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc1PGzEQxa0KVD7aW8_IUi8cCIzteB1fKkUBSgSoPbRny-udpQ67drB3K-W_xygUpZzGmvnNGz89Qr4wOBdCw4Vf9ZkL4AxAfyCHbMr5BKBSezvvA3KU8wqACy71R3IgJEjJtDwkdtlgGHy78eGBLmxofGMHpD9THNAHem_TI6ZMY0vnbiyDW98E3NBlWI1pQwuxbV-ii_0aQy7LDb1BmwZ6bX03JvxE9lvbZfz8Wo_J7-urX4ubyd2P78vF_G7iRKWHCbJKWF1JB4rVlgN3blaXTlvXGphG1rhGMtCSMa5A6aq207p44xyZsoqLY_Jtq7se6x4bV2wl25l18r1NGxOtN_9Pgv9jHuJfM1NqJkEXgdNXgRSfRsyD6X122HU2YByz4eUWV0pORUG_vkNXcUyh2HuhmOBcqKpQZ1vKpZhzwvbtMwzMS3ZmN7uCn-waeIP_hSWeARdWlO8</recordid><startdate>20220117</startdate><enddate>20220117</enddate><creator>Templeton, Evelyn M</creator><creator>Lassé, Moritz</creator><creator>Kleffmann, Torsten</creator><creator>Ellmers, Leigh J</creator><creator>Palmer, Suetonia C</creator><creator>Davidson, Trent</creator><creator>Scott, Nicola J A</creator><creator>Pickering, John W</creator><creator>Charles, Christopher J</creator><creator>Endre, Zoltan H</creator><creator>Cameron, Vicky A</creator><creator>Richards, A Mark</creator><creator>Rademaker, Miriam T</creator><creator>Pilbrow, Anna P</creator><general>MDPI AG</general><general>MDPI</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>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5735-9549</orcidid><orcidid>https://orcid.org/0000-0002-5767-794X</orcidid><orcidid>https://orcid.org/0000-0003-3147-683X</orcidid><orcidid>https://orcid.org/0000-0002-5685-9151</orcidid><orcidid>https://orcid.org/0000-0001-9807-8022</orcidid></search><sort><creationdate>20220117</creationdate><title>Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure</title><author>Templeton, Evelyn M ; Lassé, Moritz ; Kleffmann, Torsten ; Ellmers, Leigh J ; Palmer, Suetonia C ; Davidson, Trent ; Scott, Nicola J A ; Pickering, John W ; Charles, Christopher J ; Endre, Zoltan H ; Cameron, Vicky A ; Richards, A Mark ; Rademaker, Miriam T ; Pilbrow, Anna P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c369t-e163a965c071ba202cc8b3a9fbb9019e1dcd5109511270796ba4b00622e17a723</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acute Kidney Injury - 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There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date, no protein biomarkers have exhibited sufficient diagnostic or prognostic performance for widespread clinical uptake. We aimed to identify novel protein biomarkers of AKI associated with ADHF by quantifying changes in protein abundance in the kidneys that occur during ADHF development and recovery in an ovine model. Relative quantitative protein profiling was performed using sequential window acquisition of all theoretical fragment ion spectra-mass spectrometry (SWATH-MS) in kidney cortices from control sheep (
= 5), sheep with established rapid-pacing-induced ADHF (
= 8), and sheep after ~4 weeks recovery from ADHF (
= 7). Of the 790 proteins quantified, we identified 17 candidate kidney injury markers in ADHF, 1 potential kidney marker of ADHF recovery, and 2 potential markers of long-term renal impairment (differential abundance between groups of 1.2-2.6-fold, adjusted
< 0.05). Among these 20 candidate protein markers of kidney injury were 6 candidates supported by existing evidence and 14 novel candidates not previously implicated in AKI. Proteins of differential abundance were enriched in pro-inflammatory signalling pathways: glycoprotein VI (activated during ADHF development; adjusted
< 0.01) and acute phase response (repressed during recovery from ADHF; adjusted
< 0.01). New biomarkers for the early detection of AKI in ADHF may help us to evaluate effective treatment strategies to prevent mortality and improve outcomes for patients.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35055195</pmid><doi>10.3390/ijms23021009</doi><orcidid>https://orcid.org/0000-0001-5735-9549</orcidid><orcidid>https://orcid.org/0000-0002-5767-794X</orcidid><orcidid>https://orcid.org/0000-0003-3147-683X</orcidid><orcidid>https://orcid.org/0000-0002-5685-9151</orcidid><orcidid>https://orcid.org/0000-0001-9807-8022</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | International journal of molecular sciences, 2022-01, Vol.23 (2), p.1009 |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Acute Kidney Injury - blood Acute Kidney Injury - diagnosis Acute Kidney Injury - metabolism Acute Kidney Injury - urine Animals Biomarkers Biomarkers - blood Biomarkers - metabolism Biomarkers - urine Candidates Congestive heart failure Creatinine Disease Models, Animal FDA approval Glycoprotein VI Heart failure Heart Failure - blood Heart Failure - complications Heart Failure - metabolism Heart Failure - urine Humans Inflammation Injury prevention Kidneys Kinases Mass spectrometry Mass spectroscopy Mortality Patients Physiology Plasma Platelet Membrane Glycoproteins - metabolism Platelet Membrane Glycoproteins - urine Prognosis Protein folding Proteins Proteomics - methods Renal failure Sheep Signal transduction |
| title | Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure |
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