Additive Effects of Soluble TWEAK and Inflammation on Mortality in Hemodialysis Patients
Chronic kidney disease (CKD) is characterized by an exceptionally high mortality rate, primarily due to cardiovascular disease. Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and CKD. A cross-sectional st...
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| Veröffentlicht in: | Clinical journal of the American Society of Nephrology 2009-01, Vol.4 (1), p.110-118 |
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| creator | Carrero, Juan J Ortiz, Alberto Qureshi, Abdul R Martín-Ventura, Jose L Bárány, Peter Heimbürger, Olof Marrón, Belén Metry, George Snaedal, Sunna Lindholm, Bengt Egido, Jesús Stenvinkel, Peter Blanco-Colio, Luis M |
| description | Chronic kidney disease (CKD) is characterized by an exceptionally high mortality rate, primarily due to cardiovascular disease. Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and CKD.
A cross-sectional study was conducted in 218 prevalent patients (121 men; 63 +/- 14 yr) undergoing hemodialysis (HD). sTWEAK levels in relation with the patients' outcome were studied.
sTWEAK plasma levels were 208 [(165 to 272) pg/ml, median interquartile range], significantly lower than healthy controls (P < 0.0001). sTWEAK was negatively associated with inflammatory markers, such as C-reactive protein and IL-6. Overall mortality was assessed after an average follow-up of 31 mo, during which 81 patients died. After controlling for potential confounding variables, patients in the upper tertile of sTWEAK plasma levels had an increased risk of cardiovascular and all-cause mortality. A significant interaction effect between sTWEAK and IL-6 levels was found [synergy index: 2.19 (0.80, 5.93)]. Thus, the association of sTWEAK with mortality was strongest in patients with inflammation (defined as IL-6 > 7.0 pg/ml), in whom high sTWEAK strongly predicted cardiovascular and all-cause mortality. These results were confirmed in a second cohort of HD patients.
The concurrent presence of elevated sTWEAK plasma concentrations and an inflammatory environment have additive effects on mortality in HD patients. Further studies on the potential different role of sTWEAK in health and disease are warranted. |
| doi_str_mv | 10.2215/CJN.02790608 |
| format | Article |
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A cross-sectional study was conducted in 218 prevalent patients (121 men; 63 +/- 14 yr) undergoing hemodialysis (HD). sTWEAK levels in relation with the patients' outcome were studied.
sTWEAK plasma levels were 208 [(165 to 272) pg/ml, median interquartile range], significantly lower than healthy controls (P < 0.0001). sTWEAK was negatively associated with inflammatory markers, such as C-reactive protein and IL-6. Overall mortality was assessed after an average follow-up of 31 mo, during which 81 patients died. After controlling for potential confounding variables, patients in the upper tertile of sTWEAK plasma levels had an increased risk of cardiovascular and all-cause mortality. A significant interaction effect between sTWEAK and IL-6 levels was found [synergy index: 2.19 (0.80, 5.93)]. Thus, the association of sTWEAK with mortality was strongest in patients with inflammation (defined as IL-6 > 7.0 pg/ml), in whom high sTWEAK strongly predicted cardiovascular and all-cause mortality. These results were confirmed in a second cohort of HD patients.
The concurrent presence of elevated sTWEAK plasma concentrations and an inflammatory environment have additive effects on mortality in HD patients. Further studies on the potential different role of sTWEAK in health and disease are warranted.</description><identifier>ISSN: 1555-9041</identifier><identifier>EISSN: 1555-905X</identifier><identifier>DOI: 10.2215/CJN.02790608</identifier><identifier>PMID: 18945991</identifier><language>eng</language><publisher>United States: American Society of Nephrology</publisher><subject>Aged ; Biomarkers - blood ; Cardiovascular Diseases - blood ; Cardiovascular Diseases - etiology ; Cardiovascular Diseases - mortality ; Case-Control Studies ; Chronic Disease ; Cross-Sectional Studies ; Cytokine TWEAK ; Dialysis ; Female ; Humans ; Inflammation - blood ; Inflammation - etiology ; Inflammation - mortality ; Inflammation Mediators - blood ; Interleukin-6 - blood ; Kaplan-Meier Estimate ; Kidney Diseases - blood ; Kidney Diseases - complications ; Kidney Diseases - mortality ; Kidney Diseases - therapy ; Male ; Middle Aged ; Proportional Hazards Models ; Renal Dialysis - mortality ; Reproducibility of Results ; Risk Assessment ; Sweden - epidemiology ; Time Factors ; Tumor Necrosis Factors - blood ; Up-Regulation</subject><ispartof>Clinical journal of the American Society of Nephrology, 2009-01, Vol.4 (1), p.110-118</ispartof><rights>Copyright © 2009 by the American Society of Nephrology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c517t-b673bc7e56674c377f67116b00829a09b2d2d8c049e1042d4e284b5135a705ea3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615702/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2615702/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,550,723,776,780,881,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18945991$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:118178800$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Carrero, Juan J</creatorcontrib><creatorcontrib>Ortiz, Alberto</creatorcontrib><creatorcontrib>Qureshi, Abdul R</creatorcontrib><creatorcontrib>Martín-Ventura, Jose L</creatorcontrib><creatorcontrib>Bárány, Peter</creatorcontrib><creatorcontrib>Heimbürger, Olof</creatorcontrib><creatorcontrib>Marrón, Belén</creatorcontrib><creatorcontrib>Metry, George</creatorcontrib><creatorcontrib>Snaedal, Sunna</creatorcontrib><creatorcontrib>Lindholm, Bengt</creatorcontrib><creatorcontrib>Egido, Jesús</creatorcontrib><creatorcontrib>Stenvinkel, Peter</creatorcontrib><creatorcontrib>Blanco-Colio, Luis M</creatorcontrib><title>Additive Effects of Soluble TWEAK and Inflammation on Mortality in Hemodialysis Patients</title><title>Clinical journal of the American Society of Nephrology</title><addtitle>Clin J Am Soc Nephrol</addtitle><description>Chronic kidney disease (CKD) is characterized by an exceptionally high mortality rate, primarily due to cardiovascular disease. Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and CKD.
A cross-sectional study was conducted in 218 prevalent patients (121 men; 63 +/- 14 yr) undergoing hemodialysis (HD). sTWEAK levels in relation with the patients' outcome were studied.
sTWEAK plasma levels were 208 [(165 to 272) pg/ml, median interquartile range], significantly lower than healthy controls (P < 0.0001). sTWEAK was negatively associated with inflammatory markers, such as C-reactive protein and IL-6. Overall mortality was assessed after an average follow-up of 31 mo, during which 81 patients died. After controlling for potential confounding variables, patients in the upper tertile of sTWEAK plasma levels had an increased risk of cardiovascular and all-cause mortality. A significant interaction effect between sTWEAK and IL-6 levels was found [synergy index: 2.19 (0.80, 5.93)]. Thus, the association of sTWEAK with mortality was strongest in patients with inflammation (defined as IL-6 > 7.0 pg/ml), in whom high sTWEAK strongly predicted cardiovascular and all-cause mortality. These results were confirmed in a second cohort of HD patients.
The concurrent presence of elevated sTWEAK plasma concentrations and an inflammatory environment have additive effects on mortality in HD patients. Further studies on the potential different role of sTWEAK in health and disease are warranted.</description><subject>Aged</subject><subject>Biomarkers - blood</subject><subject>Cardiovascular Diseases - blood</subject><subject>Cardiovascular Diseases - etiology</subject><subject>Cardiovascular Diseases - mortality</subject><subject>Case-Control Studies</subject><subject>Chronic Disease</subject><subject>Cross-Sectional Studies</subject><subject>Cytokine TWEAK</subject><subject>Dialysis</subject><subject>Female</subject><subject>Humans</subject><subject>Inflammation - blood</subject><subject>Inflammation - etiology</subject><subject>Inflammation - mortality</subject><subject>Inflammation Mediators - blood</subject><subject>Interleukin-6 - blood</subject><subject>Kaplan-Meier Estimate</subject><subject>Kidney Diseases - blood</subject><subject>Kidney Diseases - complications</subject><subject>Kidney Diseases - mortality</subject><subject>Kidney Diseases - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Proportional Hazards Models</subject><subject>Renal Dialysis - mortality</subject><subject>Reproducibility of Results</subject><subject>Risk Assessment</subject><subject>Sweden - epidemiology</subject><subject>Time Factors</subject><subject>Tumor Necrosis Factors - blood</subject><subject>Up-Regulation</subject><issn>1555-9041</issn><issn>1555-905X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNpVkctv1DAQxi0EoqXlxhn5xIkUj-NHckFarbYPKLQSRfRmOc6k6-LEJc622v8eV7t9SSPNaOY334z0EfIB2AHnIL_Mv_08YFzXTLHqFdkFKWVRM3n5-rEWsEPepXTNmBAll2_JDlS1kHUNu-Ry1rZ-8rdIF12Hbko0dvRXDKsmIL34s5h9p3Zo6cnQBdv3dvJxoDl-xHGywU9r6gd6jH1svQ3r5BM9zwwOU9onbzobEr7f5j3y-3BxMT8uTs-OTuaz08JJ0FPRKF02TqNUSgtXat0pDaAaxipeW1Y3vOVt5ZioEZjgrUBeiUZCKa1mEm25R4qNbrrDm1Vjbkbf23FtovVm2_qbKzRSgZIy8183fJ702Lr862jDi7WXk8EvzVW8NVyB1IxngU9bgTH-W2GaTO-TwxDsgHGVjFIVlFqUGfy8Ad0YUxqxezwCzNxbZ7J15sG6jH98_tgTvPXq6fDSXy3v_Igm9TaEjHPjrm0ahAEDwMr_6d6iRA</recordid><startdate>20090101</startdate><enddate>20090101</enddate><creator>Carrero, Juan J</creator><creator>Ortiz, Alberto</creator><creator>Qureshi, Abdul R</creator><creator>Martín-Ventura, Jose L</creator><creator>Bárány, Peter</creator><creator>Heimbürger, Olof</creator><creator>Marrón, Belén</creator><creator>Metry, George</creator><creator>Snaedal, Sunna</creator><creator>Lindholm, Bengt</creator><creator>Egido, Jesús</creator><creator>Stenvinkel, Peter</creator><creator>Blanco-Colio, Luis M</creator><general>American Society of Nephrology</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>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20090101</creationdate><title>Additive Effects of Soluble TWEAK and Inflammation on Mortality in Hemodialysis Patients</title><author>Carrero, Juan J ; 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Reduced soluble TNF-like weak inducer of apoptosis (sTWEAK) plasma levels have been reported both in patients with subclinical atherosclerosis and CKD.
A cross-sectional study was conducted in 218 prevalent patients (121 men; 63 +/- 14 yr) undergoing hemodialysis (HD). sTWEAK levels in relation with the patients' outcome were studied.
sTWEAK plasma levels were 208 [(165 to 272) pg/ml, median interquartile range], significantly lower than healthy controls (P < 0.0001). sTWEAK was negatively associated with inflammatory markers, such as C-reactive protein and IL-6. Overall mortality was assessed after an average follow-up of 31 mo, during which 81 patients died. After controlling for potential confounding variables, patients in the upper tertile of sTWEAK plasma levels had an increased risk of cardiovascular and all-cause mortality. A significant interaction effect between sTWEAK and IL-6 levels was found [synergy index: 2.19 (0.80, 5.93)]. Thus, the association of sTWEAK with mortality was strongest in patients with inflammation (defined as IL-6 > 7.0 pg/ml), in whom high sTWEAK strongly predicted cardiovascular and all-cause mortality. These results were confirmed in a second cohort of HD patients.
The concurrent presence of elevated sTWEAK plasma concentrations and an inflammatory environment have additive effects on mortality in HD patients. Further studies on the potential different role of sTWEAK in health and disease are warranted.</abstract><cop>United States</cop><pub>American Society of Nephrology</pub><pmid>18945991</pmid><doi>10.2215/CJN.02790608</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Biomarkers - blood Cardiovascular Diseases - blood Cardiovascular Diseases - etiology Cardiovascular Diseases - mortality Case-Control Studies Chronic Disease Cross-Sectional Studies Cytokine TWEAK Dialysis Female Humans Inflammation - blood Inflammation - etiology Inflammation - mortality Inflammation Mediators - blood Interleukin-6 - blood Kaplan-Meier Estimate Kidney Diseases - blood Kidney Diseases - complications Kidney Diseases - mortality Kidney Diseases - therapy Male Middle Aged Proportional Hazards Models Renal Dialysis - mortality Reproducibility of Results Risk Assessment Sweden - epidemiology Time Factors Tumor Necrosis Factors - blood Up-Regulation |
| title | Additive Effects of Soluble TWEAK and Inflammation on Mortality in Hemodialysis Patients |
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