The Mitochondrial-Derived Peptide MOTS-c May Refine Mortality and Cardiovascular Risk Prediction in Chronic Hemodialysis Patients: A Multicenter Cohort Study.

IF 2.2 3区 医学 Q3 HEMATOLOGY Blood Purification Pub Date : 2024-01-01 Epub Date: 2024-08-07 DOI:10.1159/000540303
Davide Bolignano, Marta Greco, Pierangela Presta, Anila Duni, Mariateresa Zicarelli, Simone Mercuri, Efthymios Pappas, Lampros Lakkas, Michela Musolino, Katerina K Naka, Roberta Misiti, Daniela Patrizia Foti, Michele Andreucci, Giuseppe Coppolino, Evangelia Dounousi
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Abstract

Introduction: Uremic patients exhibit remarkably increased rates of mortality and cardiovascular (CV) events, but risk prediction in this setting remains difficult. Systemic mitochondrial dysfunction is pervasive in end-stage kidney disease and may contribute to CV complications. We tested the clinical significance of circulating MOTS-c, a small mitochondrial-derived peptide, as a biomarker for improving mortality and CV risk prediction in hemodialysis (HD) patients.

Methods: We conducted a prospective, observational, multicenter study on 94 prevalent HD patients. The study endpoint was a composite of all-cause mortality and non-fatal CV events. The diagnostic and prognostic capacities of predictive models based on cohort-related risk factors were tested before and after the inclusion of MOTS-c.

Results: MOTS-c levels were higher in HD patients than in controls (p < 0.001) and even more elevated (p = 0.01) in the 53 individuals experiencing the combined endpoint during follow-up (median duration: 26.5 months). MOTS-c was independently associated with the endpoint at either multivariate logistic (OR 1.020; 95% CI: 1.011-1.109; p = 0.03) or Cox regression analyses (HR 1.004; 95% CI: 1.000-1.025; p = 0.05) and the addition of this biomarker to prognostic models including the other cohort-related risk predictors (age, left ventricular mass, evidence of diastolic dysfunction, diabetes, pulse pressure) significantly improved the calibration, risk variability explanation, discrimination (receiver operating characteristic area under the curve from 0.727 to 0.743; C-index from 0.658 to 0.700), and particularly, the overall reclassification capacity (NRI 15.87%; p = 0.01).

Conclusions: In HD patients, the mitochondrial-derived peptide MOTS-c may impart significant information to refine CV risk prediction, beyond cohort-related risk factors. Future investigations are needed to generalize these findings in larger and more heterogeneous cohorts.

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线粒体衍生肽 MOTS-c 可完善慢性血液透析患者的死亡率和心血管风险预测:一项多中心队列研究。
导言 尿毒症患者的死亡率和心血管事件发生率明显增加,但在这种情况下进行风险预测仍然很困难。全身线粒体功能障碍在 ESKD 中普遍存在,并可能导致心血管并发症。我们测试了循环 MOTS-c(一种线粒体衍生的小肽)作为生物标记物的临床意义,以改善血液透析(HD)患者的死亡率和心血管风险预测。方法 我们对 94 名流行的 HD 患者进行了一项前瞻性多中心观察研究。研究终点是全因死亡率和非致死性心血管事件的综合指数。在纳入 MOTS-c 之前和之后,对基于队列相关风险因素的预测模型的诊断和预后能力进行了测试。结果 HD 患者的 MOTS-c 水平高于对照组(p<0.001),在随访期间(中位持续时间:26.5 个月)出现综合终点的 53 人中,MOTS-c 水平甚至更高(p=0.01)。在多变量逻辑分析(OR 1.020; 95%CI 1.011-1.109; p=0.03)或Cox回归分析(HR 1.004; 95%CI 1.000-1.025; p=0.05)中,MOTS-c与终点独立相关。05),将该生物标志物加入包括其他队列相关风险预测因子(年龄、LVMi、E/e'、糖尿病、脉压)的预后模型中,可显著改善校准、风险变异解释、辨别能力(ROC-AUC 从 0.727 升至 0.743;C-指数从 0.658 升至 0.700),尤其是整体再分类能力(NRI 15.87%;p=0.01)。结论 在 HD 患者中,线粒体衍生肽 MOTS-c 可为完善心血管风险预测提供重要信息,而不局限于队列相关风险因素。未来还需要进行调查,以便在规模更大、异质性更强的队列中推广这些发现。
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来源期刊
Blood Purification
Blood Purification 医学-泌尿学与肾脏学
CiteScore
5.80
自引率
3.30%
发文量
69
审稿时长
6-12 weeks
期刊介绍: Practical information on hemodialysis, hemofiltration, peritoneal dialysis and apheresis is featured in this journal. Recognizing the critical importance of equipment and procedures, particular emphasis has been placed on reports, drawn from a wide range of fields, describing technical advances and improvements in methodology. Papers reflect the search for cost-effective solutions which increase not only patient survival but also patient comfort and disease improvement through prevention or correction of undesirable effects. Advances in vascular access and blood anticoagulation, problems associated with exposure of blood to foreign surfaces and acute-care nephrology, including continuous therapies, also receive attention. Nephrologists, internists, intensivists and hospital staff involved in dialysis, apheresis and immunoadsorption for acute and chronic solid organ failure will find this journal useful and informative. ''Blood Purification'' also serves as a platform for multidisciplinary experiences involving nephrologists, cardiologists and critical care physicians in order to expand the level of interaction between different disciplines and specialities.
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