title: 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 (T50) of calciprotein particles in serum was described. We used this test to measure serum T50 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 T50 tertile was more than two times the risk among patients in the highest T50 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 T50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification.
authors.affiliation: Department of Renal Medicine, Eastern Health Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia;
authors.forename: Edward R
authors.initials: ER
authors.lastname: Smith
authors.forename: Martin L
authors.initials: ML
authors.lastname: Ford
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Tomlinson
authors.forename: Emma
authors.initials: E
authors.lastname: Bodenham
authors.forename: Lawrence P
authors.initials: LP
authors.lastname: McMahon
authors.forename: Stefan
authors.initials: S
authors.lastname: Farese
authors.forename: Chakravarthi
authors.initials: C
authors.lastname: Rajkumar
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Holt
authors.forename: Andreas
authors.initials: A
authors.lastname: Pasch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000097:blood* / Q000453:epidemiology; D015415:Biomarkers; D002114:Calcinosis / Q000097:blood* / Q000453:epidemiology; D002130:Calcium Phosphates / Q000097:blood*; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015984:Causality; D015897:Comorbidity; D003920:Diabetes Mellitus / Q000453:epidemiology; D011756:Diphosphates / Q000097:blood; D004198:Disease Susceptibility; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009026:Mortality; D010010:Osteoclasts / Q000378:metabolism; D010710:Phosphates / Q000097:blood*; D011446:Prospective Studies; D063177:Pulse Wave Analysis; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000453:epidemiology / Q000628:therapy; D012306:Risk; D012709:Serum Albumin / Q000032:analysis*; D012907:Smoking / Q000453:epidemiology; D014655:Vascular Resistance; D060749:alpha-2-HS-Glycoprotein / Q000032:analysis* / Q000737:chemistry
chemical_list: C556354:AHSG protein, human; D015415:Biomarkers; D002130:Calcium Phosphates; D011756:Diphosphates; D010710:Phosphates; D012709:Serum Albumin; D060749:alpha-2-HS-Glycoprotein; C107241:diphosphoric acid; C020243:calcium phosphate