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

doi:10.1016/j.ekir.2020.07.033

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

Kidney Int Rep. 2020 Aug 6;5(10):1729-1737. doi: 10.1016/j.ekir.2020.07.033. eCollection 2020 Oct.

Authors

Jessica Fitzpatrick¹, Esther D Kim^{2

3}, Stephen M Sozio^{3

4}, Bernard G Jaar^{2

3

4

5}, Michelle M Estrella^{6

7}, Jose M Monroy-Trujillo⁴, Rulan S Parekh^{1

2

4

8}

Affiliations

¹ Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
² Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
³ Welch Center for Prevention, Epidemiology, and Clinical Research, Baltimore, Maryland, USA.
⁴ Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
⁵ Nephrology Center of Maryland, Baltimore, Maryland, USA.
⁶ Kidney Health Research Collaborative, Department of Medicine, University of California, San Francisco, San Franscisco, California, USA.
⁷ Department of Medicine, San Francisco VA Medical Center, San Francisco, California, USA.
⁸ Division of Nephrology, Department of Pediatrics and Medicine, The Hospital for Sick Children, University Health Network and University of Toronto, Ontario, Canada.

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.

Keywords: arterial stiffness; fetuin A; fibroblast growth factor 23; hemodialysis; matrix Gla protein; osteoprotegerin.

Grants and funding

R01 DK072367/DK/NIDDK NIH HHS/United States