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

被引:53
作者
Feldreich, Tobias [1 ,2 ,3 ,4 ]
Nowak, Christoph [2 ]
Fall, Tove [3 ,4 ]
Carlsson, Axel C. [2 ,3 ,4 ]
Carrero, Juan-Jesus [5 ]
Ripsweden, Jonas [6 ]
Qureshi, Abdul Rashid [7 ]
Heimburger, Olof [7 ]
Barany, Peter [7 ]
Stenvinkel, Peter [7 ]
Vuilleumier, Nicolas [8 ,9 ]
Kalra, Philip A. [10 ,11 ]
Green, Darren [10 ,11 ]
Arnlov, Johan [1 ,2 ]
机构
[1] Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden
[2] Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden
[3] Uppsala Univ, Dept Med Sci, Uppsala, Sweden
[4] Uppsala Univ, Sci Life Lab, Uppsala, Sweden
[5] Karolinska Inst, Dept Med Epidemiol & Biostat MEB, Solna, Sweden
[6] Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol, Campus Flemingsberg, Stockholm, Sweden
[7] Karolinska Univ Hosp, Div Renal Med, Dept Clin Sci Intervent & Technol CLINTEC, Stockholm, Sweden
[8] Geneva Univ Hosp, Dept Genet Lab Med & Pathol, Geneva, Switzerland
[9] Geneva Fac Med, Dept Med Specialties, Geneva, Switzerland
[10] Univ Manchester, Manchester Acad Hlth Sci Ctr, Div Cardiovasc Sci, Manchester, Lancs, England
[11] Salford Royal NHS Fdn Trust, Dept Renal, Med, Stott Lane, Salford, Lancs, England
基金
欧盟地平线“2020”; 英国医学研究理事会; 瑞典研究理事会;
关键词
CVD; ESRD; Proteomics; KIDNEY INJURY MOLECULE-1; BIOMARKERS; RISK; KINASES; KIM-1; ASSOCIATIONS; INFLAMMATION; PROGRESSION; ACTIVATION; MODALITY;
D O I
10.1007/s40620-018-0556-5
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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 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). 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.
引用
收藏
页码:111 / 119
页数:9
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[11]   Urinary Kidney Injury Molecule 1 (KIM-1) and Interleukin 18 (IL-18) as Risk Markers for Heart Failure in Older Adults: The Health, Aging, and Body Composition (Health ABC) Study [J].
Driver, Todd H. ;
Katz, Ronit ;
Ix, Joachim H. ;
Magnani, Jared W. ;
Peralta, Carmen A. ;
Parikh, Chirag R. ;
Fried, Linda ;
Newman, Anne B. ;
Kritchevsky, Stephen B. ;
Sarnak, Mark J. ;
Shlipak, Michael G. .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2014, 64 (01) :49-56
[12]   Immune Regulation and Antitumor Effect of TIM-1 [J].
Du, Peng ;
Xiong, Ruihua ;
Li, Xiaodong ;
Jiang, Jingting .
JOURNAL OF IMMUNOLOGY RESEARCH, 2016, 2016
[13]   Urinary Biomarkers and Risk of ESRD in the Atherosclerosis Risk in Communities Study [J].
Foster, Meredith C. ;
Coresh, Josef ;
Bonventre, Joseph V. ;
Sabbisetti, Venkata S. ;
Waikar, Sushrut S. ;
Mifflin, Theodore E. ;
Nelson, Robert G. ;
Grams, Morgan ;
Feldman, Harold I. ;
Vasan, Ramachandran S. ;
Kimmel, Paul L. ;
Hsu, Chi-yuan ;
Liu, Kathleen D. .
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2015, 10 (11) :1956-1963
[14]   Cardiorenal syndrome: pathophysiological mechanism, preclinical models, novel contributors and potential therapies [J].
Fu Qiang ;
Cao Longxing ;
Li Huang ;
Wang Binghui ;
Li Zhiliang .
CHINESE MEDICAL JOURNAL, 2014, 127 (16) :3011-3018
[15]   New insights in molecular mechanisms involved in chronic kidney disease using high-resolution plasma proteome analysis [J].
Glorieux, Griet ;
Mullen, William ;
Duranton, Flore ;
Filip, Szymon ;
Gayrard, Nathalie ;
Husi, Holger ;
Schepers, Eva ;
Neirynck, Nathalie ;
Schanstra, Joost P. ;
Jankowski, Joachim ;
Mischak, Harald ;
Argiles, Angel ;
Vanholder, Raymond ;
Vlahou, Antonia ;
Klein, Julie .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2015, 30 (11) :1842-1852
[16]   Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery [J].
Gold, Larry ;
Ayers, Deborah ;
Bertino, Jennifer ;
Bock, Christopher ;
Bock, Ashley ;
Brody, Edward N. ;
Carter, Jeff ;
Dalby, Andrew B. ;
Eaton, Bruce E. ;
Fitzwater, Tim ;
Flather, Dylan ;
Forbes, Ashley ;
Foreman, Trudi ;
Fowler, Cate ;
Gawande, Bharat ;
Goss, Meredith ;
Gunn, Magda ;
Gupta, Shashi ;
Halladay, Dennis ;
Heil, Jim ;
Heilig, Joe ;
Hicke, Brian ;
Husar, Gregory ;
Janjic, Nebojsa ;
Jarvis, Thale ;
Jennings, Susan ;
Katilius, Evaldas ;
Keeney, Tracy R. ;
Kim, Nancy ;
Koch, Tad H. ;
Kraemer, Stephan ;
Kroiss, Luke ;
Le, Ngan ;
Levine, Daniel ;
Lindsey, Wes ;
Lollo, Bridget ;
Mayfield, Wes ;
Mehan, Mike ;
Mehler, Robert ;
Nelson, Sally K. ;
Nelson, Michele ;
Nieuwlandt, Dan ;
Nikrad, Malti ;
Ochsner, Urs ;
Ostroff, Rachel M. ;
Otis, Matt ;
Parker, Thomas ;
Pietrasiewicz, Steve ;
Resnicow, Daniel I. ;
Rohloff, John .
PLOS ONE, 2010, 5 (12)
[17]   Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury [J].
Ichimura, T ;
Bonventre, JV ;
Bailly, V ;
Wei, H ;
Hession, CA ;
Cate, RL ;
Sanicola, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (07) :4135-4142
[18]   Crosstalk between mitogen-activated protein kinases and mitochondria in cardiac diseases: Therapeutic perspectives [J].
Javadov, Sabzali ;
Jang, Sehwan ;
Agostini, Bryan .
PHARMACOLOGY & THERAPEUTICS, 2014, 144 (02) :202-225
[19]  
Kim HS, 2017, FREE RADIC BIOL MED, V19, P30156
[20]   Inflammation and premature aging in advanced chronic kidney disease [J].
Kooman, Jeroen P. ;
Dekker, Marijke J. ;
Usvyat, Len A. ;
Kotanko, Peter ;
van der Sande, Frank M. ;
Schalkwijk, Casper G. ;
Shiels, Paul G. ;
Stenvinkel, Peter .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2017, 313 (04) :F938-F950