Division of Nephrology, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Zerifin, Israel.
Department of Pathology, Assaf Harofeh Medical Center, Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Zerifin, Israel.
Am J Nephrol. 2018;47(4):254-265. doi: 10.1159/000488285. Epub 2018 Apr 25.
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.
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.
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, p = 0.001) and cardiovascular mortality (SI 4.81, p = 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.
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.
最近的实验研究表明，肥胖激素（一种被提议的厌食性肠道激素，是酰基胃饥饿素的生理拮抗剂）具有保护心血管的作用。我们检验了这样一个假设，即肥胖激素可以独立于炎症介质和/或酰基胃饥饿素来预测维持性血液透析（MHD）人群的预后。
这是一项对 261 名 MHD 患者进行的 6 年队列研究。研究了肥胖激素、酰基胃饥饿素、脂肪因子（瘦素和脂联素）、炎症和营养标志物、前瞻性全因和心血管死亡率。
在随访期间，共有 160 名患者死亡，其中 74 人死于心血管原因。在充分调整模型中（包括营养不良-炎症评分、白细胞介素-6 [IL-6]、脂肪因子和酰基胃饥饿素），每增加基础肥胖激素水平 1ng/ml，全因死亡的风险为 0.90（95%可信区间 0.81-0.99），心血管死亡的风险为 0.85（95%可信区间 0.73-0.99）。然而，这些关联在年龄大于 71 岁的患者亚组中更为显著：全因死亡的风险为 0.85（95%可信区间 0.73-0.98），心血管死亡的风险为 0.66（95%可信区间 0.52-0.85）。在多变量调整模型中，高 IL-6（中位数以上）和低肥胖激素（中位数以下）水平之间的相互作用增加了全因死亡率的风险（协同指数 [SI] 5.14，p=0.001）和心血管死亡率（SI 4.81，p=0.02）。在肥胖激素、肿瘤坏死因子-α、脂肪因子和酰基胃饥饿素之间也观察到相互作用，这些相互作用与死亡率风险相关。
血清肥胖激素是 MHD 患者心血管和全因死亡的生物标志物。肥胖激素在这方面的预后能力独立于炎症、营养状况、酰基胃饥饿素和脂肪因子的活性，并受年龄影响，在年龄大于 71 岁的患者中尤为明显。
