Abstract
BackgroundArterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble α-klotho (sKl).MethodsIn this prospective, single-center, observational study, arterial stiffness [measured by pulse wave velocity (PWV)] and hormones influencing mineral homeostasis, including serum FGF23 and sKl, were compared between non-dialysis CKD stages 4/5 and healthy controls at baseline and 12 months (12 m). Abdominal aortic calcification (AAC) was quantitated using lateral lumbar radiography at baseline.ResultsForty patients with CKD [mean estimated glomerular filtration rate (eGFR) 19.5 ± 6.7 mL/min/1.73m2] and 42 controls (mean eGFR 88.6 ± 12.9 mL/min/1.73m2) completed follow-up. There were no differences in age, gender and body mass index between groups. A significant increase in FGF23 [240.6 (141.9–1129.8) to 396.8 (160.3–997.7) pg/mL, p = 0.001] was observed in the CKD group but serum phosphate, corrected calcium, parathyroid hormone and sKl did not change significantly over 12 m. At baseline, CKD subjects had higher AAC prevalence [83.8% versus (vs.) 43.6%, p = 0.002] and higher aortic PWV [9.7(7.6–11.7) vs. 8.1 (7.2–9.7) m/s, p = 0.047] compared to controls. At 12 m, aortic PWV increased by 1.3 m/s (95% confidence interval, 0.56 to 2.08, p < 0.001) in the CKD cohort, with 30% of subjects showing progression from normal aortic elasticity to stiffening (PWV > 10 m/s). Serum FGF23 was associated with AAC, abnormal PWV and progression of PWV at 12 m.ConclusionsArterial stiffness and serum FGF23, both of which are associated with increased cardiovascular risk, increased over one year in individuals with CKD. Additionally, a significant association was found between serum FGF23 and arterial calcification and stiffness. Larger clinical studies and further experimental work are warranted to delineate the temporal relationship as well as the pathological mechanisms linking FGF23 and vascular disease.
Highlights
Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD)
No significant differences were observed between the groups for age, gender, body mass index (BMI), racial origin, blood pressure, use of cholecalciferol and calcium supplements
Findings in our study suggest fibroblast growth factor 23 (FGF23) may have a greater association with vascular burden compared to soluble α-klotho (sKl)
Summary
Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD) [1]. Accelerated atherosclerosis and calcification of both medial and intimal layers of coronary and systemic arteries result in reduced coronary perfusion and increased arterial stiffness, commonly measured using the well-validated methodology of pulse wave velocity (PWV) [3]. Higher PWV in patients with CKD is associated with a substantial increase in all-cause mortality and both fatal and non-fatal cardiovascular events. These associations are independent of traditional cardiovascular risk factors [4]
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