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维持性血液透析患者 4 年全因死亡率与肉碱谱的相关性。

Association between 4-year all-cause mortality and carnitine profile in maintenance hemodialysis patients.

机构信息

Departments of Medicine, Kidney Center, Tokyo Women's Medical University, Shinjuku, Tokyo, Japan.

Departments of Blood Purification, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan.

出版信息

PLoS One. 2018 Aug 22;13(8):e0201591. doi: 10.1371/journal.pone.0201591. eCollection 2018.

Abstract

BACKGROUND

Patients on dialysis are in a chronic carnitine-deficient state. This condition may be associated with abnormalities of the fatty acid and organic acid metabolisms. Carnitine is required for β-oxidation of the long-chain fatty acids; therefore, carnitine deficiency decreases the efficiency of ATP synthesis and may incur death. However, the details of this association remain unknown. We examined the relationship between β-oxidation efficiency represented by the carnitine profile and 4-year all-cause mortality in hemodialysis patients.

METHODS

The carnitine profiles of 122 hemodialysis patients were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The associations between the 4-year all-cause mortality and carnitine profile as well as the clinical backgrounds of the patients were investigated. A survival analysis was conducted by the Kaplan-Meier survival method and multivariable Cox proportional hazard analysis. The bootstrap method was performed to confirm the stability and robustness of our model.

RESULTS

Of the 122 subjects analyzed, 111 were selected and 24 died during the observation period. Stepwise multivariable Cox regression demonstrated that diabetes state [Hazard ratio (95% confidence interval), 4.981 (2.107-11.77)], age [HR (95% CI), 1.052 (1.014-1.091)], and the acetylcarnitine/(palmitoylcarnitine+octadecenoylcarnitine) [C2/(C16+C18:1)] ratio [HR (95% CI), 0.937 (0.904-0.971)] were independent significant factors of 4-year all-cause mortality. The bootstrap method confirmed the significance of these three factors.

CONCLUSION

The 4-year all-cause mortality negatively correlated with the C2/(C16+C18:1) ratio. Improvement of the impaired β-oxidation state after L-carnitine administration may ameliorate prognosis.

摘要

背景

透析患者处于慢性肉碱缺乏状态。这种情况可能与脂肪酸和有机酸代谢异常有关。肉碱是长链脂肪酸β-氧化所必需的,因此肉碱缺乏会降低 ATP 合成的效率,并可能导致死亡。然而,这种关联的细节尚不清楚。我们检查了由肉碱谱代表的β-氧化效率与血液透析患者 4 年全因死亡率之间的关系。

方法

通过液相色谱-串联质谱(LC-MS/MS)法测定 122 例血液透析患者的肉碱谱。调查了 4 年全因死亡率与肉碱谱以及患者临床背景之间的关系。采用 Kaplan-Meier 生存法和多变量 Cox 比例风险分析进行生存分析。采用自举法验证我们模型的稳定性和健壮性。

结果

在分析的 122 名受试者中,选择了 111 名,在观察期间有 24 名死亡。逐步多变量 Cox 回归表明,糖尿病状态[风险比(95%置信区间),4.981(2.107-11.77)]、年龄[HR(95%CI),1.052(1.014-1.091)]和乙酰肉碱/(棕榈酰肉碱+十八烯酰肉碱)[C2/(C16+C18:1)]比值[HR(95%CI),0.937(0.904-0.971)]是 4 年全因死亡率的独立显著因素。自举法证实了这三个因素的重要性。

结论

4 年全因死亡率与 C2/(C16+C18:1)比值呈负相关。左旋肉碱给药后改善受损的β-氧化状态可能改善预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d31/6104933/4d1dcf62aa7d/pone.0201591.g001.jpg

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