Associations of Serum Calciprotein Particle Size and Transformation Time With Arterial Calcification, Arterial Stiffness, and Mortality in Incident Hemodialysis Patients

Rationale & Objective: Characteristics of the transformation of primary to secondary calciprotein particles (CPPs) in serum, including the size of secondary CPP (CPP2) aggregates and the time of transformation (T₅₀), may be markers for arterial calcification in patients undergoing hemodialysis (HD). We examined the associations of CPP2 aggregate size and T₅₀ with arterial calcification in incident HD patients. Study Design: Prospective cohort study. Setting & Participants: Incident HD patients (n = 402 with available CPP2 measures and n = 388 with available T₅₀ measures) from the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) Study Predictors: Serum CPP2 size and T₅₀ at baseline. Outcomes: Primary outcomes were baseline coronary artery and thoracic aorta calcifications. Exploratory outcomes included baseline arterial stiffness, measured by pulse wave velocity (PWV) and ankle brachial index, and longitudinally, repeat measures of PWV and all-cause mortality. Analytical Approach: Tobit regression, multiple linear regression, Poisson regression, linear mixed-effects regression, and Cox proportional hazards regression. Results: Mean age was 55 ± 13 years, 41% were women, 71% were Black, and 57% had diabetes mellitus. Baseline CPP2 size and T₅₀ were correlated with baseline fetuin A level (r = −0.59 for CPP2 and 0.44 for T₅₀; P < 0.001 for both), but neither was associated with baseline measures of arterial calcification or arterial stiffness. Baseline CPP2 size and T₅₀ were not associated with repeat measures of PWV. During a median follow-up of 3.5 (IQR, 1.7-6.2) years, larger CPP2 was associated with higher risk for mortality (HR, 1.17 [95% CI, 1.05-1.31] per 100 nm larger CPP2 size) after adjusting for demographics and comorbid conditions, but there was no association between baseline T₅₀ and risk for mortality. Limitations: Possible imprecision in assays, small sample size, limited generalizability to incident HD populations with different racial composition, and residual confounding. Conclusions: In incident HD patients, neither CPP2 size nor T₅₀ was associated with prevalent arterial calcification and stiffness. Larger CPP2 was associated with risk for mortality, but this finding needs to be confirmed in future studies.