Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease
| العنوان: | Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease |
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| المؤلفون: | Darren Green, Nicolas Vuilleumier, Tove Fall, Abdul Rashid Qureshi, Peter Stenvinkel, Johan Ärnlöv, Peter Bárány, Tobias Feldreich, Jonas Ripsweden, Axel C. Carlsson, Olof Heimbürger, Christoph Nowak, Juan Jesus Carrero, Philip A. Kalra |
| المصدر: | Journal of Nephrology Journal of Nephrology, Vol. 32, No 1 (2019) pp. 111-119 |
| بيانات النشر: | Springer International Publishing, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Nephrology, Proteomics, Male, Time Factors, medicine.medical_treatment, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Gastroenterology, 0302 clinical medicine, Risk Factors, Urologi och njurmedicin, Prevalence, Medicine, Hepatitis A Virus Cellular Receptor 1, ddc:616, Incidence, Hazard ratio, Middle Aged, CVD, Prognosis, 3. Good health, Cardiovascular Diseases, Cohort, Original Article, Female, Hemodialysis, Adult, medicine.medical_specialty, Risk Assessment, End stage renal disease, 03 medical and health sciences, Renal Dialysis, Internal medicine, Urology and Nephrology, Humans, ESRD, Dialysis, Aged, Sweden, business.industry, Proportional hazards model, Klinisk medicin, medicine.disease, Kidney Transplantation, Kidney Failure, Chronic, Clinical Medicine, business, Biomarkers, Kidney disease |
| الوصف: | Introduction 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 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. 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 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n = 89, 37% women, mean age 46 years). Results In 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. Conclusions Our 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. Electronic supplementary material The online version of this article (10.1007/s40620-018-0556-5) contains supplementary material, which is available to authorized users. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1724-6059 1121-8428 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::00ee2c333db074034e3ace7e4d0a7f64Test http://europepmc.org/articles/PMC6373380Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....00ee2c333db074034e3ace7e4d0a7f64 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17246059 11218428 |
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