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  • Rudholm Feldreich, TobiasHögskolan Dalarna,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi,Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden,Medicinsk vetenskap,Karolinska Institutet; Uppsala universitet (author)

Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease

  • Article/chapterEnglish2019

Publisher, publication year, extent ...

  • 2018-11-29
  • Stockholm :Springer Science and Business Media LLC,2019
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-378193
  • ISSN:1121-8428
  • 10616/47529hdl
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-378193URI
  • https://doi.org/10.1007/s40620-018-0556-5DOI
  • http://hdl.handle.net/10616/47529URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:du-29000URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:140293840URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n=183, 55% women, mean age 63years, 46 cardiovascular deaths during follow-up (mean 43months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n=186, 73% women, mean age 62years, 45 cardiovascular deaths during follow-up (mean 12months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n=89, 37% women, mean age 46years).ResultsIn age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26-2.69, p=0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C=0.777 to C=0.799 and C=0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03-2.05, p=0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort.ConclusionsOur proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies.

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  • Nowak, ChristophKarolinska Institutet (author)
  • Fall, Tove,1979-Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi(Swepub:uu)tovfa878 (author)
  • Carlsson, Axel CKarolinska Institutet,Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden(Swepub:uu)axeca883 (author)
  • Carrero, Juan-JesusKarolinska Institutet (author)
  • Ripsweden, JonasKarolinska Institutet (author)
  • Qureshi, Abdul RashidKarolinska Institutet (author)
  • Heimburger, OlofKarolinska Institutet (author)
  • Barany, PeterKarolinska Institutet (author)
  • Stenvinkel, PeterKarolinska Institutet (author)
  • Vuilleumier, NicolasGeneva Univ Hosp, Dept Genet Lab Med & Pathol, Geneva, Switzerland;Geneva Fac Med, Dept Med Specialties, Geneva, Switzerland (author)
  • Kalra, Philip A.Univ Manchester, Manchester Acad Hlth Sci Ctr, Div Cardiovasc Sci, Manchester, Lancs, England;Salford Royal NHS Fdn Trust, Dept Renal, Med, Stott Lane, Salford, Lancs, England (author)
  • Green, DarrenUniv Manchester, Manchester Acad Hlth Sci Ctr, Div Cardiovasc Sci, Manchester, Lancs, England;Salford Royal NHS Fdn Trust, Dept Renal, Med, Stott Lane, Salford, Lancs, England (author)
  • Ärnlöv, Johan,1970-Högskolan Dalarna,Medicinsk vetenskap,Karolinska Institutet(Swepub:du)jan (author)
  • Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)
  • Karolinska Institutet
  • Karolinska Institutet

Related titles

  • In:JN. Journal of Nephrology (Milano. 1992)Stockholm : Springer Science and Business Media LLC32:1, s. 111-1191121-84281724-6059

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