Mortality prediction in stable hemodialysis patients is refined by YKL-40, a 40-kDa glycoprotein associated with inflammation

Chronic inflammation contributes to increased mortality in hemodialysis (HD) patients. YKL-40 is a novel marker of inflammation, tissue remodeling, and highly expressed in macrophages inside vascular lesions. Elevated levels of YKL-40 have been reported for HD patients but how it integrates into the...

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Bibliographic Details
Published in:Kidney international 2018-01, Vol.93 (1), p.221-230
Main Authors: Lorenz, Georg, Schmalenberg, Michael, Kemmner, Stephan, Haller, Bernhard, Steubl, Dominik, Pham, Dang, Schreiegg, Anita, Bachmann, Quirin, Schmidt, Alina, Haderer, Sandra, Huber, Monika, Angermann, Susanne, Günthner, Roman, Braunisch, Matthias, Hauser, Christine, Reichelt, Anna-Lena, Matschkal, Julia, Suttmann, Yana, Moog, Philipp, Stock, Konrad, Küchle, Claudius, Thürmel, Klaus, Renders, Lutz, Bauer, Axel, Baumann, Marcus, Heemann, Uwe, Luppa, Peter B., Schmaderer, Christoph
Format: Article
Language:English
Subjects:
Aged
Biomarkers - blood
cardiovascular
Chitinase-3-Like Protein 1 - blood
chronic inflammation
Cross-Sectional Studies
Female
hemodialysis
Humans
Inflammation Mediators - blood
Kidney Failure, Chronic - blood
Kidney Failure, Chronic - diagnosis
Kidney Failure, Chronic - mortality
Kidney Failure, Chronic - therapy
Male
Middle Aged
mortality
Predictive Value of Tests
Renal Dialysis - adverse effects
Renal Dialysis - mortality
Retrospective Studies
risk
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
YKL-40
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Summary:Chronic inflammation contributes to increased mortality in hemodialysis (HD) patients. YKL-40 is a novel marker of inflammation, tissue remodeling, and highly expressed in macrophages inside vascular lesions. Elevated levels of YKL-40 have been reported for HD patients but how it integrates into the proinflammatory mediator network as a predictor of mortality remains elusive. We studied serum YKL-40, Interleukin-6 (IL-6), high-sensitivity C-reactive protein, monocyte chemotactic protein-1 (MCP-1), and interferon-gamma induced protein-10 (IP-10) in 475 chronic hemodialysis patients. Patients were followed for mortality for a median of 37 [interquartile range: 25-49] months and checked for interrelation of the measured mediators. To plot cumulative incidence functions, patients were stratified into terciles per YKL-40, IL-6, MCP-1, and IP-10 levels. Multivariable Cox regression models were built to examine associations of YKL-40, IP-10, and MCP-1 with all-cause and cause-specific mortality. Net reclassification improvement was calculated for the final models containing YKL-40 and IL-6. Increased YKL-40 was independently associated with age, IP-10, and IL-6 serum levels. After adjustment for demographic and laboratory parameters, comorbidities, and IL-6, only YKL-40 significantly improved risk prediction for all-cause (hazard ratio 1.4; 95% confidence interval 1.1-1.8) and cardiovascular mortality (hazard ratio 1.5; 95% confidence interval 1.03-2.2). Thus, in contrast to other biomarkers of aberrant macrophage activation, YKL-40 reflects inflammatory activity, which is not covered by IL-6. Mechanistic and prospective studies are needed to test for causal involvement of YKL-40 and whether it might qualify as a therapeutic target.
ISSN:0085-2538
1523-1755
DOI:10.1016/j.kint.2017.07.010