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Observational Study
. 2017 Sep 4;18(1):281.
doi: 10.1186/s12882-017-0705-4.

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

Rathika Krishnasamy  1   2 , Sven-Jean Tan  3   4 , Carmel M Hawley  5   6   7 , David W Johnson  5   6   7 , Tony Stanton  5   8 , Kevin Lee  9 , David W Mudge  5   7 , Scott Campbell  5   7 , Grahame J Elder  10   11 , Nigel D Toussaint  3   4 , Nicole M Isbel  5   7
Affiliations
Observational Study

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

Rathika Krishnasamy et al. BMC Nephrol. .

Abstract

Background: 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).

Methods: 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.

Results: Forty 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.

Conclusions: 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.

Keywords: Aortic calcification; Arterial stiffness; Chronic kidney disease; Fibroblast growth factor 23; Soluble klotho.

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Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the Metro South Health Human Research Ethics Committee (HREC 2012/480). Written informed consent was obtained from all participants before commencement of baseline visit for this study.

Consent for publication

Not applicable.

Competing interest

Associate Professor Carmel Hawley has received research funding from Baxter Healthcare Pty Ltd., Shire Pty. Limited and Fresenius Medical Care. She has received travel grants from Amgen Australia. Professor David Johnson is a consultant for Baxter Healthcare Pty Ltd. and has previously received research funds from this company. He has also received speakers’ honoraria and research grants from Fresenius Medical Care and is a recipient of a National Health and Medical Council Practitioner Fellowship. Associate Professor Isbel has received research funding from Baxter Healthcare Pty Ltd., Roche Pharmaceuticals and Amgen in the form of peer-reviewed grants. She has also received travel grants from Shire Australia, Alexion Pharmaceuticals and Pfizer. Dr. Rathika Krishnasamy and Dr. Sven-Jean Tan have received speaking honoraria from Shire Australia. Associate Professor Tony Stanton has acted as a consultant to Medtronic and Novartis Pharmaceuticals. David Mudge has received travel grants, consultancy fees and speakers’ honoraria from Baxter Healthcare, Amgen and Alexion. Dr. Sven-Jean Tan is a current recipient of the Australian National Health and Medical Research Council (NHMRC) Postgraduate Research Scholarship. Associate Professor Nigel Toussaint has received research funding and speaking honoraria from Shire, Sanofi and Amgen Australia. The remaining authors have no competing financial interests to declare.

Publisher’s Note

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Figures

Fig. 1
Fig. 1
(a) Fibroblast growth factor 23 levels and (b) pulse wave velocity at baseline and follow-up in CKD and controls. Abbreviations: CKD: chronic kidney disease; FGF23: fibroblast growth factor 23; PWV: pulse wave velocity; p denotes within group comparison at baseline and follow-up
Fig. 2
Fig. 2
Correlations between fibroblast growth factor 23 and (a) abdominal aortic calcification score and (b) pulse wave velocity at baseline for the total study population. Abbreviations: AAC: abdominal aortic calcification; FGF23: fibroblast growth factor 23; PWV: pulse wave velocity
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