Serum markers of fibrosis, cardiovascular and all-cause mortality in hemodialysis patients: the AURORA trial

Author:

Salib MadonnaORCID,Girerd Sophie,Girerd Nicolas,März Winfried,Scharnagl Hubert,Massy Ziad A.,Leroy Céline,Duarte Kévin,Holdaas Hallvard,Jardine Alan G.,Schmieder Roland E.,Fellström Bengt,López-Andrés Natalia,Rossignol Patrick,Zannad Faiez

Abstract

Abstract Background Biomarkers of fibrosis are associated with outcome in several cardiovascular diseases. However, their relevance to chronic kidney disease and dialysis is uncertain, as it remains unclear how the kidneys and the dialysis procedure itself affect their elimination and degradation. We aimed to investigate the relationship of the blood levels of two markers associated with fibrosis: procollagen type I C-terminal pro-peptide (PICP) and galectin-3 (Gal-3) with mortality in dialysis patients. Methods Procollagen type I C-terminal pro-peptide and galectin-3 were measured at baseline in 2773 patients enrolled in the AURORA trial, investigating the effect of rosuvastatin on cardiovascular outcomes, in patients on hemodialysis, and their interaction with CV death or all-cause mortality using survival models. The added prognostic value of these biomarkers was assessed by the net reclassification improvement (NRI). Results The median follow-up period was 3.8 years. Blood concentrations of PICP and Gal-3 were significantly associated with CV death [adjusted HR per 1 SD = 1.11 (1.02–1.20) and SD = 1.20 (1.10–1.31), respectively] and all-cause mortality (all adjusted p < 0.001). PICP and Gal-3 had a synergistic effect with regard to CV death and all-cause mortality (interaction p = 0.04 and 0.01, respectively). Adding PICP, Gal-3 and their interaction on top of clinical and biological covariates, resulted in significantly improved prognostic accuracy NRI = 0.080 (0.019–0.143) for CV death. Conclusion In dialysis patients, concomitant increase in PICP and Gal-3 concentrations are associated with higher rates of CV death. These results suggest that concomitantly raised PICP and Gal-3 may reflect an activated fibrogenesis relevant to risk stratification in dialysis, raising the hypothesis that anti-fibrotic therapy may be beneficial for cardiovascular protection in such patients. Graphic abstract

Funder

H2020 Marie Skłodowska-Curie Actions

RHU Fight-HF

AstraZeneca

Abbott GmbH

Publisher

Springer Science and Business Media LLC

Subject

Cardiology and Cardiovascular Medicine,General Medicine

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