Serum Calcification Propensity and Clinical Events in CKD

Author:

Bundy Joshua D.ORCID,Cai Xuan,Mehta Rupal C.,Scialla Julia J.ORCID,de Boer Ian H.,Hsu Chi-yuanORCID,Go Alan S.,Dobre Mirela A.ORCID,Chen Jing,Rao Panduranga S.,Leonard Mary B.,Lash James P.,Block Geoffrey A.,Townsend Raymond R.,Feldman Harold I.,Smith Edward R.,Pasch Andreas,Isakova Tamara,

Abstract

Background and objectivesPatients with CKD are at high risk for cardiovascular disease, ESKD, and mortality. Vascular calcification is one pathway through which cardiovascular disease risks are increased. We hypothesized that a novel measure of serum calcification propensity is associated with cardiovascular disease events, ESKD, and all-cause mortality among patients with CKD stages 2–4.Design, setting, participants, & measurementsAmong 3404 participants from the prospective, longitudinal Chronic Renal Insufficiency Cohort Study, we quantified calcification propensity as the transformation time (T50) from primary to secondary calciprotein particles, with lower T50 corresponding to higher calcification propensity. We used multivariable-adjusted Cox proportional hazards regression models to assess the associations of T50 with risks of adjudicated atherosclerotic cardiovascular disease events (myocardial infarction, stroke, and peripheral artery disease), adjudicated heart failure, ESKD, and mortality.ResultsThe mean T50 was 313 (SD 79) minutes. Over an average 7.1 (SD 3.1) years of follow-up, we observed 571 atherosclerotic cardiovascular disease events, 633 heart failure events, 887 ESKD events, and 924 deaths. With adjustment for traditional cardiovascular disease risk factors, lower T50 was significantly associated with higher risk of atherosclerotic cardiovascular disease (hazard ratio [HR] per SD lower T50, 1.14; 95% confidence interval [95% CI], 1.05 to 1.25), ESKD within 3 years from baseline (HR per SD lower T50, 1.68; 95% CI, 1.52 to 1.86), and all-cause mortality (HR per SD lower T50, 1.16; 95% CI, 1.09 to 1.24), but not heart failure (HR per SD lower T50, 1.06; 95% CI, 0.97 to 1.15). After adjustment for eGFR and 24-hour urinary protein, T50 was not associated with risks of atherosclerotic cardiovascular disease, ESKD, and mortality.ConclusionsAmong patients with CKD stages 2–4, higher serum calcification propensity is associated with atherosclerotic cardiovascular disease events, ESKD, and all-cause mortality, but this association was not independent of kidney function.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_10_28_CJN04710419.mp3

Funder

National Institute of Diabetes and Digestive and Kidney Disorders

Dr. Bundy is supported by the National Heart, Lung, and Blood Institute

NIDDK

NHLBI

Perelman School of Medicine at the University of Pennsylvania

Clinical and Translational Science Collaborative of Cleveland

Michigan Institute for Clinical and Health Research

University of Illinois at Chicago

Kaiser Permanente

Publisher

American Society of Nephrology (ASN)

Subject

Transplantation,Nephrology,Critical Care and Intensive Care Medicine,Epidemiology

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