612 - Serum Calcification Propensity and Association with Cardiovascular Risk in Children with Chronic Kidney Disease

Publication Number: 612.6711

Uche Nwaogazie, University of New Mexico School of Medicine, Albuquerque, NM, United States; Chris Penney, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Jarcy Zee, Childrens Hospital of Philadelphia, Philadelphia, PA, United States; Lawrence Copelovitch, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; mark M. Mitsnefes, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Joseph T. Flynn, University of Washington School of Medicine, Seattle, WA, United States; Bradley A. Warady, Children's Mercy, Kansas City, MO, United States; Susan L. Furth, Children's Hospital of Philadelphia, Philadelphia, PA, United States; Michelle Denburg, Children's Hospital of Philadelphia, Philadelphia, PA, United States

Background: Many patients with chronic kidney disease (CKD) suffer significant cardiovascular comorbidities including vascular calcification. Currently used techniques to detect vascular calcification do not quantify the intrinsic propensity of serum to develop calcifications. The T50 test is a functional nanoparticle based in vitro test that time-dependently assesses the ex vivo serum calcification propensity; Its potential utility is supported by studies in adults with CKD showing that shorter T50 predicts cardiovascular and all-cause mortality and vascular calcification.

Objective: We examined the association of serum calcification propensity by T50 with cardiovascular measures in children with CKD.

Design/Methods: 233 participants from the Chronic Kidney Disease in Children (CKiD) cohort study with stored serum at visits (years 1, 3, and 5) with cardiovascular measures were included. The T50 test was performed at Calciscon laboratories, Nidau, Switzerland. Potential determinants of T50 (CKD stage, serum calcium, phosphate, intact PTH, bicarbonate and albumin) were evaluated using multivariable linear mixed effects regression. The association of T50 with left ventricular mass index (LVMI), left ventricular hypertrophy (LVH), carotid intima-media thickness (cIMT), and ambulatory arterial stiffness index (AASI) was determined using multivariable linear mixed effects models for continuous outcomes and a logistic model for LVH. We compared the association of T50 versus Calcium x Phosphate product (CaxPhos) with cardiovascular measures using separate univariate mixed models.

Results: The median age at initial visit was 12.0 (5.2, 15.3) years and 63% of the cohort was male. The median T50 value was 340 (IQR: 267 to 388) minutes. Higher serum phosphate was independently associated with shorter T50, while higher serum calcium, bicarbonate, and albumin were associated with longer T50 (Table 1). Shorter T50 was associated with greater LVMI after adjusting for age, blood pressure, and CKD severity (Table 2). The lowest quartile of T50 was associated with increased odds of LVH, though the statistical significance was attenuated in the multivariable model (Table 3). T50 was not significantly associated with cIMT or AASI. Compared to CaxPhos, T50 performed better as a predictor of LVMI and LVH with a higher conditional R^2 and lower AIC.

Conclusion(s): Among children with CKD, a shorter T50 (higher serum calcification propensity) was associated with higher phosphate (but lower calcium) and higher LVMI and may be a useful predictor of cardiovascular risk.

Table 1: Univariate and Multivariable Linear Mixed Effects Models of Determinants of T50
Table 1.pdf

Table 2: Univariate and Multivariable Linear Mixed Effects Models of Association of T50 with LVMI
Table 2.pdf

Table 3: Univariate and Multivariable Logistic Mixed Effects Model of Association of T50 with LVH
Table 3.pdf