The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early Chronic Kidney Disease
A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin fr...
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| description | A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (>43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P 43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P |
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We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (>43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P <0.001. Kaplan-Meier survival analysis demonstrated participants with cFLC >43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P <0.001). Elevated cFLC levels were independently associated with worse survival (Hazard ratio: 1.50; 95% confidence interval: 1.04-2.16; P=0.03). Other independent risk factors for worse survival were: older age, male gender, previous cardiovascular event, lower eGFR and higher high sensitivity C-reactive protein (hsCRP). To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0129980</identifier><identifier>PMID: 26132658</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Aged, 80 and over ; Analysis ; Arthritis ; Binding sites ; Biomarkers ; Biomarkers - blood ; C-reactive protein ; Cardiovascular diseases ; Case-Control Studies ; Chains ; Chronic illnesses ; Chronic kidney failure ; Confidence intervals ; Diabetes ; Epidermal growth factor receptors ; Female ; Hazard assessment ; Health aspects ; Health risk assessment ; Health risks ; Hospitals ; Humans ; Immunoglobulin kappa-Chains - blood ; Immunoglobulin lambda-Chains - blood ; Immunoglobulins ; Inflammation ; Kidney diseases ; Light ; Light chains ; Lupus ; Lymphoma ; Male ; Markers ; Medicine ; Monoclonal gammopathy ; Mortality ; Obesity ; Patients ; Population ; Primary care ; Recruitment ; Renal Insufficiency, Chronic - blood ; Risk analysis ; Risk factors ; Studies ; Survival ; Values</subject><ispartof>PloS one, 2015-07, Vol.10 (7), p.e0129980-e0129980</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Assi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Assi et al 2015 Assi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-310932bd792ace87947690751aac5eb2183fecd1fc06bbb215ad1abb243cabea3</citedby><cites>FETCH-LOGICAL-c692t-310932bd792ace87947690751aac5eb2183fecd1fc06bbb215ad1abb243cabea3</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/PMC4489104/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4489104/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26132658$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Stover, Cordula M.</contributor><creatorcontrib>Assi, Lakhvir K</creatorcontrib><creatorcontrib>McIntyre, Natasha</creatorcontrib><creatorcontrib>Fraser, Simon</creatorcontrib><creatorcontrib>Harris, Scott</creatorcontrib><creatorcontrib>Hutchison, Colin A</creatorcontrib><creatorcontrib>McIntyre, Chris W</creatorcontrib><creatorcontrib>Cockwell, Paul</creatorcontrib><creatorcontrib>Taal, Maarten W</creatorcontrib><title>The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early Chronic Kidney Disease</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (>43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P <0.001. Kaplan-Meier survival analysis demonstrated participants with cFLC >43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P <0.001). Elevated cFLC levels were independently associated with worse survival (Hazard ratio: 1.50; 95% confidence interval: 1.04-2.16; P=0.03). Other independent risk factors for worse survival were: older age, male gender, previous cardiovascular event, lower eGFR and higher high sensitivity C-reactive protein (hsCRP). To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation.</description><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Arthritis</subject><subject>Binding sites</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>C-reactive protein</subject><subject>Cardiovascular diseases</subject><subject>Case-Control Studies</subject><subject>Chains</subject><subject>Chronic illnesses</subject><subject>Chronic kidney failure</subject><subject>Confidence intervals</subject><subject>Diabetes</subject><subject>Epidermal growth factor receptors</subject><subject>Female</subject><subject>Hazard assessment</subject><subject>Health aspects</subject><subject>Health risk assessment</subject><subject>Health risks</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunoglobulin kappa-Chains - blood</subject><subject>Immunoglobulin lambda-Chains - blood</subject><subject>Immunoglobulins</subject><subject>Inflammation</subject><subject>Kidney diseases</subject><subject>Light</subject><subject>Light chains</subject><subject>Lupus</subject><subject>Lymphoma</subject><subject>Male</subject><subject>Markers</subject><subject>Medicine</subject><subject>Monoclonal gammopathy</subject><subject>Mortality</subject><subject>Obesity</subject><subject>Patients</subject><subject>Population</subject><subject>Primary care</subject><subject>Recruitment</subject><subject>Renal Insufficiency, Chronic - blood</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Studies</subject><subject>Survival</subject><subject>Values</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk89u1DAQxiMEolB4AwSWkBAcdrFj598FqVpaWFFURAtXa-JMNq68drGdln0KXhlvd1t1UQ8ohzie3_eNZ-LJsheMThmv2PtzN3oLZnrhLE4py5umpg-yJ6zh-aTMKX94Z72XPQ3hnNKC12X5ONvLS8bzsqifZH_OBiQHITilIWpnSYvxCtGSb86slHEpA5m5ZastduQU_bgkRx6RHOvFEMlsAG1T3Cq00W8MwHbkq_MRjI4rksJz2-lL3Y1gArnScSCH4M0qab2zWpEvurO4Ih91QAj4LHvUJxCfb9_72Y-jw7PZ58nxyaf57OB4osomjxPOaKqt7aomB4V11YiqbGhVMABVYJuzmveoOtYrWrZt-i6gY5AWgitoEfh-9mrje2FckNteBsmSe1U0jRCJmG-IzsG5vPB6CX4lHWh5veH8QoKPWhmUtSoqBXUvCgGipapuQPSQM2i6gqt8ne3DNtvYLrHbdMvsmO5GrB7kwl1KIeqG0fVh3m4NvPs1YohyqYNCY8CiG6_PzStOC1Yk9PU_6P3VbakFpAK07V3Kq9am8kDklAlRCp6o6T1UejpcapUuXq_T_o7g3Y4gMRF_xwWMIcj56ff_Z09-7rJv7rADgolDcGZc37iwC4oNqLwLwWN_22RG5Xpubroh13Mjt3OTZC_v_qBb0c2g8L-pixT_</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Assi, Lakhvir K</creator><creator>McIntyre, Natasha</creator><creator>Fraser, Simon</creator><creator>Harris, Scott</creator><creator>Hutchison, Colin A</creator><creator>McIntyre, Chris W</creator><creator>Cockwell, Paul</creator><creator>Taal, Maarten W</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20150701</creationdate><title>The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early Chronic Kidney Disease</title><author>Assi, Lakhvir K ; McIntyre, Natasha ; Fraser, Simon ; Harris, Scott ; Hutchison, Colin A ; McIntyre, Chris W ; Cockwell, Paul ; Taal, Maarten W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-310932bd792ace87947690751aac5eb2183fecd1fc06bbb215ad1abb243cabea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Arthritis</topic><topic>Binding sites</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>C-reactive protein</topic><topic>Cardiovascular diseases</topic><topic>Case-Control Studies</topic><topic>Chains</topic><topic>Chronic illnesses</topic><topic>Chronic kidney failure</topic><topic>Confidence intervals</topic><topic>Diabetes</topic><topic>Epidermal growth factor receptors</topic><topic>Female</topic><topic>Hazard assessment</topic><topic>Health aspects</topic><topic>Health risk assessment</topic><topic>Health risks</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunoglobulin kappa-Chains - blood</topic><topic>Immunoglobulin lambda-Chains - blood</topic><topic>Immunoglobulins</topic><topic>Inflammation</topic><topic>Kidney diseases</topic><topic>Light</topic><topic>Light chains</topic><topic>Lupus</topic><topic>Lymphoma</topic><topic>Male</topic><topic>Markers</topic><topic>Medicine</topic><topic>Monoclonal gammopathy</topic><topic>Mortality</topic><topic>Obesity</topic><topic>Patients</topic><topic>Population</topic><topic>Primary care</topic><topic>Recruitment</topic><topic>Renal Insufficiency, Chronic - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Assi, Lakhvir K</au><au>McIntyre, Natasha</au><au>Fraser, Simon</au><au>Harris, Scott</au><au>Hutchison, Colin A</au><au>McIntyre, Chris W</au><au>Cockwell, Paul</au><au>Taal, Maarten W</au><au>Stover, Cordula M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early Chronic Kidney Disease</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-07-01</date><risdate>2015</risdate><volume>10</volume><issue>7</issue><spage>e0129980</spage><epage>e0129980</epage><pages>e0129980-e0129980</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>A major component of increased mortality risk in people with chronic kidney disease (CKD) is associated with non-traditional cardiovascular risk factors including markers of inflammation. We studied whether a novel marker of systemic inflammation, elevated serum combined polyclonal immunoglobulin free light chains (cFLC), was an independent risk factor for increased all-cause mortality in people with CKD stage 3. In a prospective community based cohort study, 1695 participants with stage 3 CKD and no cases of monoclonal gammopathy had cFLC concentrations measured. cFLC levels were determined using the summation of Freelite kappa and lambda assays. All other bioclinical variables were collected at the time of sample collection. Kaplan-Meier plots and Cox proportional hazards analysis was used to assess the relationship between high cFLC levels (>43.3 mg/L) and mortality. There were 167 deaths (10%) after a median of 1375 days. cFLC levels at recruitment were higher in participants who died compared with those who were alive at the end of the study; median: 46.5 mg/L (IQR: 36.1-65.4 mg/L) and 35.4 mg/L (28.1-46.6 mg/L) respectively, P <0.001. Kaplan-Meier survival analysis demonstrated participants with cFLC >43.3 mg/L levels had an increased risk of mortality compared to people with normal cFLC levels (P <0.001). Elevated cFLC levels were independently associated with worse survival (Hazard ratio: 1.50; 95% confidence interval: 1.04-2.16; P=0.03). Other independent risk factors for worse survival were: older age, male gender, previous cardiovascular event, lower eGFR and higher high sensitivity C-reactive protein (hsCRP). To conclude, high cFLC levels predict increased mortality in people with stage 3 CKD, independent of established risk factors and other markers of inflammation.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26132658</pmid><doi>10.1371/journal.pone.0129980</doi><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aged Aged, 80 and over Analysis Arthritis Binding sites Biomarkers Biomarkers - blood C-reactive protein Cardiovascular diseases Case-Control Studies Chains Chronic illnesses Chronic kidney failure Confidence intervals Diabetes Epidermal growth factor receptors Female Hazard assessment Health aspects Health risk assessment Health risks Hospitals Humans Immunoglobulin kappa-Chains - blood Immunoglobulin lambda-Chains - blood Immunoglobulins Inflammation Kidney diseases Light Light chains Lupus Lymphoma Male Markers Medicine Monoclonal gammopathy Mortality Obesity Patients Population Primary care Recruitment Renal Insufficiency, Chronic - blood Risk analysis Risk factors Studies Survival Values |
| title | The Association between Polyclonal Combined Serum Free Light Chain Concentration and Mortality in Individuals with Early 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=2025-01-12T06%3A36%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Association%20between%20Polyclonal%20Combined%20Serum%20Free%20Light%20Chain%20Concentration%20and%20Mortality%20in%20Individuals%20with%20Early%20Chronic%20Kidney%20Disease&rft.jtitle=PloS%20one&rft.au=Assi,%20Lakhvir%20K&rft.date=2015-07-01&rft.volume=10&rft.issue=7&rft.spage=e0129980&rft.epage=e0129980&rft.pages=e0129980-e0129980&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0129980&rft_dat=%3Cgale_plos_%3EA420144643%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1692759944&rft_id=info:pmid/26132658&rft_galeid=A420144643&rft_doaj_id=oai_doaj_org_article_8c57ca8f454a4b0c89a4fa21a9d53c2a&rfr_iscdi=true |