L-C Desbiens1,2, A Sidibé1,3, R-V Ung1, C Fortier1,2, M Munger1,2, Y-P Wang1,2, S-K Bisson1,2, K Marquis1, M Agharazii1,2, F Mac-Way4,5,6. 1. CHU de Québec Research Center, Endocrinology and Nephrology Axis, Quebec, Canada. 2. Faculty and Department of Medicine, Université Laval, Quebec, Canada. 3. Department of Social and Preventive Medicine, Faculty of Medicine, Université Laval, Quebec, Canada. 4. CHU de Québec Research Center, Endocrinology and Nephrology Axis, Quebec, Canada. fabrice.mac-way@mail.chuq.qc.ca. 5. Faculty and Department of Medicine, Université Laval, Quebec, Canada. fabrice.mac-way@mail.chuq.qc.ca. 6. CHU de Québec Research Center, L'Hôtel-Dieu de Québec Hospital, 10 McMahon, Quebec City, G1R 2J6, Canada. fabrice.mac-way@mail.chuq.qc.ca.
Abstract
We performed a case-control study on 130 age- and sex-matched hemodialysis patients. In multivariate analysis, we observed that FGF23 levels were associated with fracture incidence and that soluble α-klotho levels were associated with the aortic-brachial arterial stiffness ratio. INTRODUCTION: New bone markers such as sclerostin, Dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23), and α-klotho have been identified as potential key players in bone and vascular abnormalities of chronic kidney disease. Therefore, we aimed to assess whether these markers are associated with fractures, bone metabolism, and vascular stiffness in dialysis patients. METHODS: In a prospective hemodialysis cohort, where plasma samples and vascular assessment were performed at baseline, we matched patients who experienced a fracture during follow-up with sex- and age-matched non-fractured patients on a 1:4 ratio. Sclerostin, DKK1, α-klotho, FGF23, and markers of bone formation (alkaline phosphatase and procollagen type 1-N terminal propeptide [P1NP]) and bone resorption (tartrate-resistant acid phosphatase 5b [TRAP5b]) were measured in baseline plasma samples. Aortic-brachial pulse wave velocity ratio, a blood pressure independent measure of arterial stiffness, was used to assess vascular stiffness at baseline. RESULTS: We included 130 hemodialysis patients (26 fractured, 104 non-fractured) with a median follow-up of 42 months and a median age of 72 years. In multivariate Cox regression models, high FGF23 levels were associated with increased fracture incidence (adjusted HR = 2.97; 95% CI 1.18, 7.43). α-Klotho levels were associated with bone formation but not resorption markers. In both univariate and multivariable adjusted models, α-klotho levels were inversely associated with the aortic-brachial pulse wave velocity ratio (β = - 0.070; 95% CI - 0.133, - 0.006). CONCLUSIONS: These results suggest a role for FGF23/klotho axis on bone and vascular metabolism in dialysis populations.
We performed a case-control study on 130 age- and sex-matched hemodialysis patients. In multivariate analysis, we observed that FGF23 levels were associated with fracture incidence and that soluble α-klotho levels were associated with the aortic-brachial arterial stiffness ratio. INTRODUCTION: New bone markers such as sclerostin, Dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23), and α-klotho have been identified as potential key players in bone and vascular abnormalities of chronic kidney disease. Therefore, we aimed to assess whether these markers are associated with fractures, bone metabolism, and vascular stiffness in dialysis patients. METHODS: In a prospective hemodialysis cohort, where plasma samples and vascular assessment were performed at baseline, we matched patients who experienced a fracture during follow-up with sex- and age-matched non-fractured patients on a 1:4 ratio. Sclerostin, DKK1, α-klotho, FGF23, and markers of bone formation (alkaline phosphatase and procollagen type 1-N terminal propeptide [P1NP]) and bone resorption (tartrate-resistant acid phosphatase 5b [TRAP5b]) were measured in baseline plasma samples. Aortic-brachial pulse wave velocity ratio, a blood pressure independent measure of arterial stiffness, was used to assess vascular stiffness at baseline. RESULTS: We included 130 hemodialysis patients (26 fractured, 104 non-fractured) with a median follow-up of 42 months and a median age of 72 years. In multivariate Cox regression models, high FGF23 levels were associated with increased fracture incidence (adjusted HR = 2.97; 95% CI 1.18, 7.43). α-Klotho levels were associated with bone formation but not resorption markers. In both univariate and multivariable adjusted models, α-klotho levels were inversely associated with the aortic-brachial pulse wave velocity ratio (β = - 0.070; 95% CI - 0.133, - 0.006). CONCLUSIONS: These results suggest a role for FGF23/klotho axis on bone and vascular metabolism in dialysis populations.
Authors: Mark D Danese; John Kim; Quan V Doan; Michelle Dylan; Robert Griffiths; Glenn M Chertow Journal: Am J Kidney Dis Date: 2006-01 Impact factor: 8.860
Authors: M Kuro-o; Y Matsumura; H Aizawa; H Kawaguchi; T Suga; T Utsugi; Y Ohyama; M Kurabayashi; T Kaname; E Kume; H Iwasaki; A Iida; T Shiraki-Iida; S Nishikawa; R Nagai; Y I Nabeshima Journal: Nature Date: 1997-11-06 Impact factor: 49.962
Authors: S Thambiah; R Roplekar; P Manghat; I Fogelman; W D Fraser; D Goldsmith; Geeta Hampson Journal: Calcif Tissue Int Date: 2012-04-21 Impact factor: 4.333
Authors: Nancy E Lane; Neeta Parimi; Maripat Corr; Wei Yao; Jane A Cauley; Carrie M Nielson; Joseph H Ix; Deborah Kado; Eric Orwoll Journal: J Bone Miner Res Date: 2013-11 Impact factor: 6.741
Authors: Isabelle Piec; Christopher Washbourne; Jonathan Tang; Emily Fisher; Julie Greeves; Sarah Jackson; William D Fraser Journal: Calcif Tissue Int Date: 2016-01-09 Impact factor: 4.333