The Mitochondrial-Derived Peptide MOTS-c May Refine Mortality and Cardiovascular Risk Prediction in Chronic Hemodialysis Patients: A Multicenter Cohort Study.
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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引用次数: 0
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.
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.