Quantification of angiotensin II-regulated proteins in urine of patients with polycystic and other chronic kidney diseases by selected reaction monitoring
Angiotensin-II (Ang II) mediates progression of autosomal-dominant polycystic kidney disease (ADPKD) and other chronic kidney diseases (CKD). However, markers of kidney Ang II activity are lacking. We previously defined 83 Ang II-regulated proteins in vitro, which reflected kidney Ang II activity in...
Gespeichert in:
| Veröffentlicht in: | Clinical proteomics 2016-08, Vol.13 (1), p.16-16, Article 16 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 16 |
|---|---|
| container_issue | 1 |
| container_start_page | 16 |
| container_title | Clinical proteomics |
| container_volume | 13 |
| creator | Konvalinka, Ana Batruch, Ihor Tokar, Tomas Dimitromanolakis, Apostolos Reid, Shelby Song, Xuewen Pei, York Drabovich, Andrei P Diamandis, Eleftherios P Jurisica, Igor Scholey, James W |
| description | Angiotensin-II (Ang II) mediates progression of autosomal-dominant polycystic kidney disease (ADPKD) and other chronic kidney diseases (CKD). However, markers of kidney Ang II activity are lacking. We previously defined 83 Ang II-regulated proteins in vitro, which reflected kidney Ang II activity in vivo.
In this study, we developed selected reaction monitoring (SRM) assays for quantification of Ang II-regulated proteins in urine of ADPKD and CKD patients. We demonstrated that 47 of 83 Ang II-regulated transcripts were differentially expressed in cystic compared to normal kidney tissue. We then developed SRM assays for 18 Ang II-regulated proteins overexpressed in cysts and/or secreted in urine. Methods that yielded CV ≤ 6 % for control proteins, and recovery ~100 % were selected. Heavy-labeled peptides corresponding to 13 identified Ang II-regulated peptides were spiked into urine samples of 17 ADPKD patients, 9 patients with CKD predicted to have high kidney Ang II activity and 11 healthy subjects. Samples were then digested and analyzed on triple-quadrupole mass spectrometer in duplicates.
Calibration curves demonstrated linearity (R(2) > 0.99) and within-run CVs |
| doi_str_mv | 10.1186/s12014-016-9117-x |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4974759</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A468814321</galeid><sourcerecordid>A468814321</sourcerecordid><originalsourceid>FETCH-LOGICAL-c497t-c8df49a39a2b33aa0bb2fd255f0fee03b4b184e71c559edb0d3118b4d34563423</originalsourceid><addsrcrecordid>eNptkt1qFTEUhQdRbK0-gDcSEMSbqfmbn9wIpVg9UBBBr0Mm2TMTnUmOSUY7r9KnNeOppQckFwl7f2sl2ayieEnwOSFt_S4SigkvMalLQUhT3jwqTklViRLTpnq8nTkta07qk-JZjN8xpoKL9mlxQhsuREPxaXH7ZVEu2d5qlax3yPdIucH6BC5ah3a7MsCwTCqBQfuQy9ZFlBtLsA42ep914FJEv20a0d5Pq15jsjrbGOTTCAHpMXiXKz-scbAiYyOoCBF1K4owgd68Ayj99wFzRpPP7sPz4kmvpggv7vaz4tvVh6-Xn8rrzx93lxfXpeaiSaVuTc-FYkLRjjGlcNfR3tCq6nEPgFnHO9JyaIjOkwHTYcPy8DpuGK9qxik7K94ffPdLN4PR-TdBTXIf7KzCKr2y8rjj7CgH_0vm63lTiWzw9s4g-J8LxCRnGzVMk3LglyhJSzCrWNvWGX19QAc1gbSu99lRb7i84HXbEs4oydT5f6i8DMxWewe9zfUjwZsHghHUlMbop2WbaDwGyQHUwccYoL__JsFyy5Q8ZErmTMktU_Ima149nM-94l-I2B8L2Mtt</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1810353886</pqid></control><display><type>article</type><title>Quantification of angiotensin II-regulated proteins in urine of patients with polycystic and other chronic kidney diseases by selected reaction monitoring</title><source>Springer Online Journals Complete</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central Open Access</source><source>PubMed Central</source><source>Springer Nature OA/Free Journals</source><creator>Konvalinka, Ana ; Batruch, Ihor ; Tokar, Tomas ; Dimitromanolakis, Apostolos ; Reid, Shelby ; Song, Xuewen ; Pei, York ; Drabovich, Andrei P ; Diamandis, Eleftherios P ; Jurisica, Igor ; Scholey, James W</creator><creatorcontrib>Konvalinka, Ana ; Batruch, Ihor ; Tokar, Tomas ; Dimitromanolakis, Apostolos ; Reid, Shelby ; Song, Xuewen ; Pei, York ; Drabovich, Andrei P ; Diamandis, Eleftherios P ; Jurisica, Igor ; Scholey, James W</creatorcontrib><description>Angiotensin-II (Ang II) mediates progression of autosomal-dominant polycystic kidney disease (ADPKD) and other chronic kidney diseases (CKD). However, markers of kidney Ang II activity are lacking. We previously defined 83 Ang II-regulated proteins in vitro, which reflected kidney Ang II activity in vivo.
In this study, we developed selected reaction monitoring (SRM) assays for quantification of Ang II-regulated proteins in urine of ADPKD and CKD patients. We demonstrated that 47 of 83 Ang II-regulated transcripts were differentially expressed in cystic compared to normal kidney tissue. We then developed SRM assays for 18 Ang II-regulated proteins overexpressed in cysts and/or secreted in urine. Methods that yielded CV ≤ 6 % for control proteins, and recovery ~100 % were selected. Heavy-labeled peptides corresponding to 13 identified Ang II-regulated peptides were spiked into urine samples of 17 ADPKD patients, 9 patients with CKD predicted to have high kidney Ang II activity and 11 healthy subjects. Samples were then digested and analyzed on triple-quadrupole mass spectrometer in duplicates.
Calibration curves demonstrated linearity (R(2) > 0.99) and within-run CVs < 9 % in the concentration range of 7/13 peptides. Peptide concentrations were normalized by urine creatinine. Deamidated peptide forms were monitored, and accounted for <15 % of the final concentrations. Urine excretion rates of proteins BST1, LAMB2, LYPA1, RHOB and TSP1 were significantly different (p < 0.05, one-way ANOVA) between patients with CKD, those with ADPKD and healthy controls. Urine protein excretion rates were highest in CKD patients and lowest in ADPKD patients. Univariate analysis demonstrated significant association between urine protein excretion rates of most proteins and disease group (p < 0.05, ANOVA) as well as sex (p < 0.05, unpaired t test). Multivariate analysis across protein concentration, age and sex demonstrated good separation between ADPKD and CKD patients.
We have optimized methods for quantification of Ang II-regulated proteins, and we demonstrated that they reflected differences in underlying kidney disease in this pilot study. High urine excretion of Ang II-regulated proteins in CKD patients likely reflects high kidney Ang II activity. Low excretion in ADPKD appears related to lack of communication between cysts and tubules. Future studies will determine whether urine excretion rate of Ang II-regulated proteins correlates with kidney Ang II activity in larger cohorts of chronic kidney disease patients.</description><identifier>ISSN: 1542-6416</identifier><identifier>EISSN: 1559-0275</identifier><identifier>DOI: 10.1186/s12014-016-9117-x</identifier><identifier>PMID: 27499720</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Angiotensin ; Chronic kidney failure ; Comparative analysis ; Proteins</subject><ispartof>Clinical proteomics, 2016-08, Vol.13 (1), p.16-16, Article 16</ispartof><rights>COPYRIGHT 2016 BioMed Central Ltd.</rights><rights>The Author(s) 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c497t-c8df49a39a2b33aa0bb2fd255f0fee03b4b184e71c559edb0d3118b4d34563423</citedby><cites>FETCH-LOGICAL-c497t-c8df49a39a2b33aa0bb2fd255f0fee03b4b184e71c559edb0d3118b4d34563423</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/PMC4974759/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4974759/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27499720$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Konvalinka, Ana</creatorcontrib><creatorcontrib>Batruch, Ihor</creatorcontrib><creatorcontrib>Tokar, Tomas</creatorcontrib><creatorcontrib>Dimitromanolakis, Apostolos</creatorcontrib><creatorcontrib>Reid, Shelby</creatorcontrib><creatorcontrib>Song, Xuewen</creatorcontrib><creatorcontrib>Pei, York</creatorcontrib><creatorcontrib>Drabovich, Andrei P</creatorcontrib><creatorcontrib>Diamandis, Eleftherios P</creatorcontrib><creatorcontrib>Jurisica, Igor</creatorcontrib><creatorcontrib>Scholey, James W</creatorcontrib><title>Quantification of angiotensin II-regulated proteins in urine of patients with polycystic and other chronic kidney diseases by selected reaction monitoring</title><title>Clinical proteomics</title><addtitle>Clin Proteomics</addtitle><description>Angiotensin-II (Ang II) mediates progression of autosomal-dominant polycystic kidney disease (ADPKD) and other chronic kidney diseases (CKD). However, markers of kidney Ang II activity are lacking. We previously defined 83 Ang II-regulated proteins in vitro, which reflected kidney Ang II activity in vivo.
In this study, we developed selected reaction monitoring (SRM) assays for quantification of Ang II-regulated proteins in urine of ADPKD and CKD patients. We demonstrated that 47 of 83 Ang II-regulated transcripts were differentially expressed in cystic compared to normal kidney tissue. We then developed SRM assays for 18 Ang II-regulated proteins overexpressed in cysts and/or secreted in urine. Methods that yielded CV ≤ 6 % for control proteins, and recovery ~100 % were selected. Heavy-labeled peptides corresponding to 13 identified Ang II-regulated peptides were spiked into urine samples of 17 ADPKD patients, 9 patients with CKD predicted to have high kidney Ang II activity and 11 healthy subjects. Samples were then digested and analyzed on triple-quadrupole mass spectrometer in duplicates.
Calibration curves demonstrated linearity (R(2) > 0.99) and within-run CVs < 9 % in the concentration range of 7/13 peptides. Peptide concentrations were normalized by urine creatinine. Deamidated peptide forms were monitored, and accounted for <15 % of the final concentrations. Urine excretion rates of proteins BST1, LAMB2, LYPA1, RHOB and TSP1 were significantly different (p < 0.05, one-way ANOVA) between patients with CKD, those with ADPKD and healthy controls. Urine protein excretion rates were highest in CKD patients and lowest in ADPKD patients. Univariate analysis demonstrated significant association between urine protein excretion rates of most proteins and disease group (p < 0.05, ANOVA) as well as sex (p < 0.05, unpaired t test). Multivariate analysis across protein concentration, age and sex demonstrated good separation between ADPKD and CKD patients.
We have optimized methods for quantification of Ang II-regulated proteins, and we demonstrated that they reflected differences in underlying kidney disease in this pilot study. High urine excretion of Ang II-regulated proteins in CKD patients likely reflects high kidney Ang II activity. Low excretion in ADPKD appears related to lack of communication between cysts and tubules. Future studies will determine whether urine excretion rate of Ang II-regulated proteins correlates with kidney Ang II activity in larger cohorts of chronic kidney disease patients.</description><subject>Angiotensin</subject><subject>Chronic kidney failure</subject><subject>Comparative analysis</subject><subject>Proteins</subject><issn>1542-6416</issn><issn>1559-0275</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNptkt1qFTEUhQdRbK0-gDcSEMSbqfmbn9wIpVg9UBBBr0Mm2TMTnUmOSUY7r9KnNeOppQckFwl7f2sl2ayieEnwOSFt_S4SigkvMalLQUhT3jwqTklViRLTpnq8nTkta07qk-JZjN8xpoKL9mlxQhsuREPxaXH7ZVEu2d5qlax3yPdIucH6BC5ah3a7MsCwTCqBQfuQy9ZFlBtLsA42ep914FJEv20a0d5Pq15jsjrbGOTTCAHpMXiXKz-scbAiYyOoCBF1K4owgd68Ayj99wFzRpPP7sPz4kmvpggv7vaz4tvVh6-Xn8rrzx93lxfXpeaiSaVuTc-FYkLRjjGlcNfR3tCq6nEPgFnHO9JyaIjOkwHTYcPy8DpuGK9qxik7K94ffPdLN4PR-TdBTXIf7KzCKr2y8rjj7CgH_0vm63lTiWzw9s4g-J8LxCRnGzVMk3LglyhJSzCrWNvWGX19QAc1gbSu99lRb7i84HXbEs4oydT5f6i8DMxWewe9zfUjwZsHghHUlMbop2WbaDwGyQHUwccYoL__JsFyy5Q8ZErmTMktU_Ima149nM-94l-I2B8L2Mtt</recordid><startdate>20160805</startdate><enddate>20160805</enddate><creator>Konvalinka, Ana</creator><creator>Batruch, Ihor</creator><creator>Tokar, Tomas</creator><creator>Dimitromanolakis, Apostolos</creator><creator>Reid, Shelby</creator><creator>Song, Xuewen</creator><creator>Pei, York</creator><creator>Drabovich, Andrei P</creator><creator>Diamandis, Eleftherios P</creator><creator>Jurisica, Igor</creator><creator>Scholey, James W</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160805</creationdate><title>Quantification of angiotensin II-regulated proteins in urine of patients with polycystic and other chronic kidney diseases by selected reaction monitoring</title><author>Konvalinka, Ana ; Batruch, Ihor ; Tokar, Tomas ; Dimitromanolakis, Apostolos ; Reid, Shelby ; Song, Xuewen ; Pei, York ; Drabovich, Andrei P ; Diamandis, Eleftherios P ; Jurisica, Igor ; Scholey, James W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c497t-c8df49a39a2b33aa0bb2fd255f0fee03b4b184e71c559edb0d3118b4d34563423</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Angiotensin</topic><topic>Chronic kidney failure</topic><topic>Comparative analysis</topic><topic>Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Konvalinka, Ana</creatorcontrib><creatorcontrib>Batruch, Ihor</creatorcontrib><creatorcontrib>Tokar, Tomas</creatorcontrib><creatorcontrib>Dimitromanolakis, Apostolos</creatorcontrib><creatorcontrib>Reid, Shelby</creatorcontrib><creatorcontrib>Song, Xuewen</creatorcontrib><creatorcontrib>Pei, York</creatorcontrib><creatorcontrib>Drabovich, Andrei P</creatorcontrib><creatorcontrib>Diamandis, Eleftherios P</creatorcontrib><creatorcontrib>Jurisica, Igor</creatorcontrib><creatorcontrib>Scholey, James W</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical proteomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Konvalinka, Ana</au><au>Batruch, Ihor</au><au>Tokar, Tomas</au><au>Dimitromanolakis, Apostolos</au><au>Reid, Shelby</au><au>Song, Xuewen</au><au>Pei, York</au><au>Drabovich, Andrei P</au><au>Diamandis, Eleftherios P</au><au>Jurisica, Igor</au><au>Scholey, James W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Quantification of angiotensin II-regulated proteins in urine of patients with polycystic and other chronic kidney diseases by selected reaction monitoring</atitle><jtitle>Clinical proteomics</jtitle><addtitle>Clin Proteomics</addtitle><date>2016-08-05</date><risdate>2016</risdate><volume>13</volume><issue>1</issue><spage>16</spage><epage>16</epage><pages>16-16</pages><artnum>16</artnum><issn>1542-6416</issn><eissn>1559-0275</eissn><abstract>Angiotensin-II (Ang II) mediates progression of autosomal-dominant polycystic kidney disease (ADPKD) and other chronic kidney diseases (CKD). However, markers of kidney Ang II activity are lacking. We previously defined 83 Ang II-regulated proteins in vitro, which reflected kidney Ang II activity in vivo.
In this study, we developed selected reaction monitoring (SRM) assays for quantification of Ang II-regulated proteins in urine of ADPKD and CKD patients. We demonstrated that 47 of 83 Ang II-regulated transcripts were differentially expressed in cystic compared to normal kidney tissue. We then developed SRM assays for 18 Ang II-regulated proteins overexpressed in cysts and/or secreted in urine. Methods that yielded CV ≤ 6 % for control proteins, and recovery ~100 % were selected. Heavy-labeled peptides corresponding to 13 identified Ang II-regulated peptides were spiked into urine samples of 17 ADPKD patients, 9 patients with CKD predicted to have high kidney Ang II activity and 11 healthy subjects. Samples were then digested and analyzed on triple-quadrupole mass spectrometer in duplicates.
Calibration curves demonstrated linearity (R(2) > 0.99) and within-run CVs < 9 % in the concentration range of 7/13 peptides. Peptide concentrations were normalized by urine creatinine. Deamidated peptide forms were monitored, and accounted for <15 % of the final concentrations. Urine excretion rates of proteins BST1, LAMB2, LYPA1, RHOB and TSP1 were significantly different (p < 0.05, one-way ANOVA) between patients with CKD, those with ADPKD and healthy controls. Urine protein excretion rates were highest in CKD patients and lowest in ADPKD patients. Univariate analysis demonstrated significant association between urine protein excretion rates of most proteins and disease group (p < 0.05, ANOVA) as well as sex (p < 0.05, unpaired t test). Multivariate analysis across protein concentration, age and sex demonstrated good separation between ADPKD and CKD patients.
We have optimized methods for quantification of Ang II-regulated proteins, and we demonstrated that they reflected differences in underlying kidney disease in this pilot study. High urine excretion of Ang II-regulated proteins in CKD patients likely reflects high kidney Ang II activity. Low excretion in ADPKD appears related to lack of communication between cysts and tubules. Future studies will determine whether urine excretion rate of Ang II-regulated proteins correlates with kidney Ang II activity in larger cohorts of chronic kidney disease patients.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>27499720</pmid><doi>10.1186/s12014-016-9117-x</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1542-6416 |
| ispartof | Clinical proteomics, 2016-08, Vol.13 (1), p.16-16, Article 16 |
| issn | 1542-6416 1559-0275 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4974759 |
| source | Springer Online Journals Complete; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; PubMed Central; Springer Nature OA/Free Journals |
| subjects | Angiotensin Chronic kidney failure Comparative analysis Proteins |
| title | Quantification of angiotensin II-regulated proteins in urine of patients with polycystic and other chronic kidney diseases by selected reaction monitoring |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T16%3A11%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Quantification%20of%20angiotensin%20II-regulated%20proteins%20in%20urine%20of%20patients%20with%20polycystic%20and%20other%20chronic%20kidney%20diseases%20by%20selected%20reaction%20monitoring&rft.jtitle=Clinical%20proteomics&rft.au=Konvalinka,%20Ana&rft.date=2016-08-05&rft.volume=13&rft.issue=1&rft.spage=16&rft.epage=16&rft.pages=16-16&rft.artnum=16&rft.issn=1542-6416&rft.eissn=1559-0275&rft_id=info:doi/10.1186/s12014-016-9117-x&rft_dat=%3Cgale_pubme%3EA468814321%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1810353886&rft_id=info:pmid/27499720&rft_galeid=A468814321&rfr_iscdi=true |