Cell-free DNA as a marker for the outcome of end-stage renal disease patients on haemodialysis

Author:

Coimbra Susana12,Rocha Susana3,Nascimento Henrique45,Valente Maria João4ORCID,Catarino Cristina4,Rocha-Pereira Petronila16,Sameiro-Faria Maria17,Oliveira José Gerardo89,Madureira José10,Fernandes João Carlos11,Miranda Vasco12,Belo Luís4,Bronze-da-Rocha Elsa4,Santos-Silva Alice4

Affiliation:

1. UCIBIO/REQUIMTE, Porto, Portugal

2. CESPU, Institute of Research and Advanced Training in Health Sciences and Technologies (IINFACTS), Gandra-Paredes, Portugal

3. LAQV/REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal

4. UCIBIO/REQUIMTE, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal

5. Neurology Service, University Hospital Centre, Porto, Portugal

6. Health Science Research Centre, University of Beira Interior, Covilhã, Portugal

7. Hemodialysis Clinic Hospital Agostinho Ribeiro, Felgueiras, Portugal

8. Hemodialysis Clinic of Porto (CHP), Porto, Portugal

9. Center for Health Technology and Services Research (CINTESIS), Faculty of Medicine, University of Porto, Porto, Portugal

10. NefroServe, Hemodialysis Clinic of Barcelos, Barcelos, Portugal

11. NefroServe Hemodialysis Clinic of Viana do Castelo, Viana do Castelo, Portugal

12. Hemodialysis Clinic of Gondomar, Gondomar, Portugal

Abstract

Abstract Background DNA damage and inflammation are common in end-stage renal disease (ESRD). Our aim was to evaluate the levels of circulating cell-free DNA (cfDNA) and the relationship with inflammation, anaemia, oxidative stress and haemostatic disturbances in ESRD patients on dialysis. By performing a 1-year follow-up study, we also aimed to evaluate the predictive value of cfDNA for the outcome of ESRD patients. Methods A total of 289 ESRD patients on dialysis were enrolled in the study: we evaluated cfDNA, haemogram, serum iron, hepcidin, inflammatory and oxidative stress markers, and haemostasis. Events and causes of deaths were recorded throughout the follow-up period. Results ESRD patients, as compared with controls, presented significantly higher levels of cfDNA, hepcidin, and inflammatory and oxidative stress markers, and significantly lower values of iron and anaemia-related haemogram parameters. The all-cause mortality rate was 9.7%; compared with alive patients, deceased patients (n = 28) were older and presented significantly higher values of inflammatory markers and of cfDNA, which was almost 2-fold higher. Furthermore, cfDNA was the best predictor of all-cause mortality and cardiovascular mortality in ESRD patients, in both unadjusted and adjusted models for basic confounding factors in dialysis. Conclusions Our data show cfDNA to be a valuable predictive marker of prognosis in ESRD patients on dialysis treatment; high levels of cfDNA were associated with a poor outcome.

Funder

FCT/MCTES

North Portugal Regional Coordination and Development Commission

FEDER/COMPETE 2020

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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