Progression of arterial stiffness is associated with changes in bone mineral markers in advanced CKD

• Published in: BMC nephrology Vol. 18; no. 1; p. 281
• Main Authors: Krishnasamy, Rathika, Tan, Sven-Jean, Hawley, Carmel M, Johnson, David W, Stanton, Tony, Lee, Kevin, Mudge, David W, Campbell, Scott, Elder, Grahame J, Toussaint, Nigel D, Isbel, Nicole M
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 04.09.2017; BioMed Central; BMC
• Subjects: Aged; Aorta; Aortic calcification; Arterial stiffness; Arteriosclerosis; Atherosclerosis; Biomarkers - blood; Body mass; Body mass index; Bone Density - physiology; Calcification; Calcification (ectopic); Calcium phosphates; Cardiovascular disease; Cardiovascular diseases; Chronic kidney disease; Chronic kidney failure; Coronary vessels; Development and progression; Dialysis; Disease Progression; Epidermal growth factor receptors; Female; Fibroblast growth factor 23; Fibroblast growth factors; Fibroblast Growth Factors - blood; Fibroblasts; Follow-Up Studies; Glomerular filtration rate; Glomerular Filtration Rate - physiology; Growth factors; Homeostasis; Humans; Ischemia; Kidney diseases; Kidney transplantation; Klotho protein; Laboratories; Longitudinal Studies; Male; Metabolism; Middle Aged; Mortality; Nephrology; Parathyroid; Parathyroid hormone; Prospective Studies; Proteins; Pulse Wave Analysis - methods; Radiography; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - diagnostic imaging; Risk factors; Smooth muscle; Soluble klotho; Urine; Vascular Stiffness - physiology; Soluble klotho; Chronic kidney disease; Aortic calcification; Arterial stiffness; Fibroblast growth factor 23
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-017-0705-4

Arterial 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). In 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. Forty patients with CKD [mean estimated glomerular filtration rate (eGFR) 19.5 ± 6.7 mL/min/1.73m ] and 42 controls (mean eGFR 88.6 ± 12.9 mL/min/1.73m ) 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. Arterial 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.