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

• Published in: American journal of kidney diseases Vol. 77; no. 3; pp. 346 - 354
• Main Authors: Chen, Wei, Fitzpatrick, Jessica, Monroy-Trujillo, Jose M., Sozio, Stephen M., Jaar, Bernard G., Estrella, Michelle M., Serrano, Jishyra, Anokhina, Viktoriya, Miller, Benjamin L., Melamed, Michal L., Bushinsky, David A., Parekh, Rulan S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2021
• Subjects: Adult; Aged; alpha-2-HS-Glycoprotein - metabolism; Ankle Brachial Index; ankle brachial index (ABI); Aortic Diseases - metabolism; Aortic Diseases - physiopathology; arterial calcification; arterial calcification (CAC); arterial stiffness; Calciprotein particle (CPP); calcium phosphate particles; Calcium Phosphates - metabolism; Cohort Studies; Coronary Artery Disease - metabolism; Coronary Artery Disease - physiopathology; CPP size; end-stage renal disease (ESRD); Female; fetuin A; hemodialysis (HD); Humans; Kidney Failure, Chronic - metabolism; Kidney Failure, Chronic - therapy; Linear Models; Longitudinal Studies; Male; Middle Aged; Mortality; Nanoparticles; Particle Size; Proportional Hazards Models; Prospective Studies; Pulse Wave Analysis; Renal Dialysis; serum albumin; thoracic aortic calcification (TAC); Time Factors; transformation time; vascular calcification; Vascular Calcification - metabolism; Vascular Calcification - physiopathology; Vascular Stiffness - physiology; arterial stiffness; CPP size; thoracic aortic calcification (TAC); calcium phosphate particles; hemodialysis (HD); vascular calcification; transformation time; ankle brachial index (ABI); fetuin A; serum albumin; arterial calcification (CAC); end-stage renal disease (ESRD); arterial calcification; mortality; Calciprotein particle (CPP)
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1053/j.ajkd.2020.05.031

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.
Prospective cohort study.
Incident HD patients (n=402with available CPP2 measures and n=388with available T50 measures) from the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease (PACE) Study
Serum CPP2 size and T50 at baseline.
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.
Tobit regression, multiple linear regression, Poisson regression, linear mixed-effects regression, and Cox proportional hazards regression.
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 100nm larger CPP2 size) after adjusting for demographics and comorbid conditions, but there was no association between baseline T50 and risk for mortality.
Possible imprecision in assays, small sample size, limited generalizability to incident HD populations with different racial composition, and residual confounding.
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.