Serum Calcification Propensity Predicts All-Cause Mortality in Predialysis CKD

Abstract

Medial arterial calcification is accelerated in patients with CKD and strongly associated with increased arterial rigidity and cardiovascular mortality. Recently, a novel in vitro blood test that provides an overall measure of calcification propensity by monitoring the maturation time (T 50 ) of calciprotein particles in serum was described. We used this test to measure serum T 50 in a prospective cohort of 184 patients with stages 3 and 4 CKD, with a median of 5.3 years of follow-up. At baseline, the major determinants of serum calcification propensity included higher serum phosphate, ionized calcium, increased bone osteoclastic activity, and lower free fetuin-A, plasma pyrophosphate, and albumin concentrations, which accounted for 49% of the variation in this parameter. Increased serum calcification propensity at baseline independently associated with aortic pulse wave velocity in the complete cohort and progressive aortic stiffening over 30 months in a subgroup of 93 patients. After adjustment for demographic, renal, cardiovascular, and biochemical covariates, including serum phosphate, risk of death among patients in the lowest T 50 tertile was more than two times the risk among patients in the highest T 50 tertile (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1 to 5.4; P=0.04). This effect was lost, however, after additional adjustment for aortic stiffness, suggesting a shared causal pathway. Longitudinally, serum calcification propensity measurements remained temporally stable (intraclass correlation=0.81). These results suggest that serum T 50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification.

Serum Calcification Propensity Is a Strong and Independent Determinant of Cardiac and All-Cause Mortality in Kidney Transplant Recipients

“…Our findings are in line with recent studies describing increased mortality at lower T 50 levels in patients with CKD (22) and in KTRs (23). Moreover, despite differences in the Table S1.…”

“…We were surprised not to find an association with T 50 . Arterial calcification and stiffness are known to be associated in CKD (34), and lower T 50 has been associated with progression in arterial stiffness (22). The discrepancy in results in our study may be due to the fact that APWV is a composite of functional and structural components (29,35).…”

“…Progression in APWV varies from 0.08 m/s per year in healthy normotensive persons and 0.15 m/s per year in treated hypertensive persons (31) to 0.84 m/s per year in hemodialysis patients (33). Considerable variability existed in APWV progression in our cohort, and 26.4% of patients increased by >1 m/s, a proportion of progressors similar to the study in CKD (22). We were surprised not to find an association with T 50 .…”

“…long T 50 ) ( Figure S1B) reflects intact calcification resistance. The structure of the primary CPPs is determined mainly by fetuin-A and albumin, whereas their stability is determined mainly by phosphate, calcium, magnesium, bicarbonate and pyrophosphate (21)(22)(23)). …”

“…An accelerated transformation time from primary to secondary CPPs is associated with increased all-cause mortality and long-term progressive aortic stiffness in elderly patients with stage 3 or 4 chronic kidney disease (CKD) (22). An association with all-cause and cardiovascular mortality was described recently in prevalent KTRs (23).…”