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.

Increased CPP fetuin-A levels reflect an increasingly procalcific milieu and are associated with increased aortic stiffness in patients with pre-dialysis CKD.

Abstract-Aortic stiffness and chronic kidney disease are closely linked by shared risk factors and associated increased cardiovascular mortality. At lower levels of renal function, aortic stiffness is independently associated with glomerular filtration rate. However, the longitudinal impact of aortic stiffness on renal function has not been reported previously. A cohort of 133 patients with chronic kidney disease stages 3 and 4 (estimated glomerular filtration rate: 15 to 59 mL/min per 1.73 m 2 ) underwent prospective measurement of arterial stiffness parameters and monitoring of renal function. Aortic pulse wave velocity measurement was performed in 120 patients. The mean age was 69Ϯ12 years (meanϮSD; 103 men, 30 women, and 23.3% diabetic). Mean systolic blood pressure was 155Ϯ21 mm Hg, and mean diastolic blood pressure was 83Ϯ11 mm Hg. The mean Modification of Diet in Renal Disease estimated glomerular filtration rate was 32Ϯ11 mL/min per 1.73 m 2 . Change in renal function was measured using reciprocal creatinine plots and the dichotomous combined end point of Ն25% decline in renal function or start of renal replacement therapy. After stepwise multivariate analysis, aortic pulse wave velocity was independently associated with gradient of reciprocal creatinine plot (rϭ0.46; Pϭ0.014). In multivariate analysis of the end point of Ն25% decline in renal function or start of renal replacement therapy, independent predictors were aortic pulse wave velocity (rϭ0.48; Pϭ0.002), systolic blood pressure (rϭ0.17; Pϭ0.039), and urine protein:creatinine ratio (rϭ0.20; Pϭ0.021). We, therefore, conclude that aortic stiffening is independently associated with rate of change in renal function in patients with chronic kidney disease stages 3 and 4. (Hypertension. 2010;55:1110-1115.) Key Words: aorta Ⅲ pulse pressure Ⅲ microvessels Ⅲ kidney Ⅲ creatinine Ⅲ pulse pressure Ⅲ renal insufficiency C hronic kidney disease (CKD) is a common condition, affecting 10% to 13% of the population of the United States, 1 associated with a dramatically increased cardiovascular (CV) mortality, which increases with severity of renal impairment. This excess CV risk is in part attributed to an increase of traditional risk factors among people with CKD 2 but may also relate to the complex metabolic and vascular changes of CKD, including arterial stiffening. Aortic stiffness increases progressively as renal function declines 3 and has been independently associated with CV mortality in patients with renal failure. 4,5 Although much research has investigated the role of aortic stiffening in the causation of CV disease in patients with CKD, less attention has been paid to its potential etiologic role in the causation and progression of renal impairment. Aortic stiffening causes increased systolic blood pressure (BP; SBP) and widened pulse pressure (PP), both factors associated in longitudinal studies with increased rate of decline of renal function. 6,7 In addition, aortic stiffening results in loss of the dampening of ventricular ejection and could lead ...