Serum Calcification Propensity and Clinical Events in CKD

Abstract

Background and objectives: Patients 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, & measurements: Among 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.

Results: The 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.

Conclusions: Among 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.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_10_28_CJN04710419.mp3.

Keywords: atherosclerosis; cardiovascular disease; chronic kidney disease; chronic kidney failure; chronic renal insufficiency; clinical epidemiology; confidence intervals; end-stage renal disease; follow-up studies; glomerular filtration rate; heart failure; humans; mortality; myocardial infarction; peripheral arterial disease; prospective studies; risk factors; stroke; vascular calcification.