Supplementary Material for: Serum Obestatin: A Biomarker of Cardiovascular and All-Cause Mortality in Hemodialysis Patients

<b><i>Background:</i></b> Recent experimental studies have suggested that obestatin, a proposed anorexigenic gut hormone and a physiological opponent of acyl-ghrelin, has protective cardiovascular effects. We tested the hypothesis that obestatin is independent of inflammatory mediators and/or acyl-ghrelin in predicting outcomes of the maintenance hemodialysis (MHD) population. <b><i>Methods:</i></b> It was a 6-year cohort study on 261 MHD patients. Obestatin, acyl-ghrelin, adipokines (leptin and adiponectin), markers of inflammation and nutrition, prospective all-cause and cardiovascular mortality were studied. <b><i>Results:</i></b> During the follow-up, 160 patients died in total, with 74 deaths due to cardiovascular causes. For each ng/mL increase in baseline obestatin level in fully adjusted models (including malnutrition-inflammation score, Interleukin-6 [IL-6], adipokines and acyl-ghrelin), the hazard for death from all causes was 0.90 (95% CI 0.81–0.99) and for cardiovascular death 0.85 (95% CI 0.73–0.99). However, these associations were more robust in the subgroup of patients aged above 71 years: 0.85 (95% CI 0.73–0.98) for all-cause death and 0.66 (95% CI 0.52–0.85) for cardiovascular death. An interaction between high IL-6 (above median) and low obestatin (below median) levels for increased risk of all-cause mortality (synergy index [SI] 5.14, <i>p</i> = 0.001) and cardiovascular mortality (SI 4.81, <i>p</i> = 0.02) emerged in the development of multivariable adjusted models. Interactions were also observed between obestatin, Tumor necrosis factor-alpha, adipokines and acyl-ghrelin, which were associated with mortality risk. <b><i>Conclusion:</i></b> Serum obestatin behaves as a biomarker for cardiovascular and all-cause mortality in MHD patients. The prognostic ability of obestatin in this regard is independent of inflammation, nutritional status, acyl-ghrelin’s and adipokines’ activity and is modified by age being very prominent in patients older than 71 years