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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 (2018): Mortality prediction in stable hemodialysis patients is refined by YKL-40, a 40-kDa glycoprotein associated with inflammation. In: Kidney International, Vol. 93, No. 1: pp. 221-230
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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.