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

Georg Lorenz, Michael Schmalenberg, Stephan Kemmner, Bernhard Haller, Dominik Steubl, Dang Pham, Anita Schreiegg, Quirin Bachmann, Alina Schmidt, Sandra Haderer, Monika Huber, Susanne Angermann, Roman Günthner, Matthias Braunisch, Christine Hauser, Anna Lena Reichelt, Julia Matschkal, Yana Suttmann, Philipp Moog, Konrad StockClaudius Küchle, Klaus Thürmel, Lutz Renders, Axel Bauer, Marcus Baumann, Uwe Heemann, Peter B. Luppa, Christoph Schmaderer

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)221-230
Number of pages10
JournalKidney International
Volume93
Issue number1
DOIs
StatePublished - Jan 2018
Externally publishedYes

Keywords

  • YKL-40
  • cardiovascular
  • chronic inflammation
  • hemodialysis
  • mortality
  • risk

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