Calcification Biomarkers, Subclinical Vascular Disease, and Mortality Among Multiethnic Dialysis Patients

Jessica Fitzpatrick, Esther D. Kim, Stephen M. Sozio, Bernard G. Jaar, Michelle M. Estrella, Jose M. Monroy-Trujillo, Rulan S. Parekh

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Vascular calcification and stiffness are associated with higher mortality and cardiovascular disease in hemodialysis patients, but the underlying mechanism is not well elucidated and previous studies have been contradictory. We sought to determine the association of circulating calcification biomarkers with calcification, stiffness, and mortality in a multiethnic incident dialysis population. Methods: Among 391 incident hemodialysis participants enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study, we examined the cross-sectional associations of baseline fibroblast growth factor 23 (FGF23), desphospho-uncarboxylated matrix Gla protein (dp-ucMGP), fetuin-A, and osteoprotegerin (OPG) according to total coronary artery calcium score (CAC, using the Agatston calcification criteria) at baseline, vascular stiffness (pulse wave velocity [PWV]) over 4 study visits, and all-cause mortality. Results: Patients’ mean age was 55 years; 40% were female, 72% were African American, and 58% had diabetes. Higher OPG and FGF23 were associated with a 1.09-fold (per 5-pmol/l increase in OPG; 95% confidence interval [CI]: 1.01–1.17) and 1.12-fold (per increase of 100 log RU/ml in FGF23; 95% CI: 1.02‒1.34) higher prevalence of CAC, independent of demographics, comorbidities, dialysis factors, and serum klotho levels. Higher OPG was associated with higher baseline PWV. Higher FGF23 was associated with lower PWV over follow-up. dp-ucMGP and fetuin-A were not associated with either CAC or vascular stiffness. After adjustment, circulating biomarkers were not associated with mortality risk. Conclusion: Several circulating calcification biomarkers were only modestly associated with subclinical cardiovascular disease in an incident multiethnic hemodialysis population; none were associated with mortality. Understanding whether these associations persist in larger, diverse hemodialysis populations is warranted before planning trials.

Original languageEnglish (US)
Pages (from-to)1729-1737
Number of pages9
JournalKidney International Reports
Volume5
Issue number10
DOIs
StatePublished - Oct 2020

Keywords

  • arterial stiffness
  • fetuin A
  • fibroblast growth factor 23
  • hemodialysis
  • matrix Gla protein
  • osteoprotegerin

ASJC Scopus subject areas

  • Ophthalmology
  • Nephrology

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