The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis

R C Shroff; V Shah; M P Hiorns; M Schoppet; L C Hofbauer; G Hawa; L J Schurgers; A Singhal; I Merryweather; P Brogan; C Shanahan; J Deanfield; L Rees

doi:10.1093/ndt/gfn226

The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis

R C Shroff, V Shah, M P Hiorns, M Schoppet, L C Hofbauer, G Hawa, L J Schurgers, A Singhal, I Merryweather, P Brogan, C Shanahan, J Deanfield, L Rees

Cardiovascular Sciences

Research output: Contribution to journal › Article › peer-review

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Abstract

Background. Vascular calcification occurs in the majority of patients with chronic kidney disease, but a subset of patients does not develop calcification despite exposure to a similar uraemic environment. Physiological inhibitors of calcification, fetuin-A, osteoprotegerin (OPG) and undercarboxylated-matrix Gla protein (uc-MGP) may play a role in preventing the development and progression of ectopic calcification, but there are scarce and conflicting data from clinical studies. Methods. We measured fetuin-A, OPG and uc-MGP in 61 children on dialysis and studied their associations with clinical, biochemical and vascular measures. Results. Fetuin-A and OPG were higher and uc-MGP lower in dialysis patients than controls. In controls, fetuin-A and OPG increased with age. Fetuin-A showed an inverse correlation with dialysis vintage (P = 0.0013), time-averaged serum phosphate (P = 0.03) and hs-CRP (P = 0.001). Aortic pulse wave velocity (PWV) and augmentation index showed a negative correlation with fetuin-A while a positive correlation was seen with PWV and OPG. Patients with calcification had lower fetuin-A and higher OPG than those without calcification. On multiple linear regression analysis Fetuin-A independently predicted aortic PWV (P = 0.004, ss = -0.45, model R-2 = 48%) and fetuin-A and OPG predicted cardiac calcification (P = 0.02, ss = -0.29 and P = 0.014, ss = 0.33, respectively, model R-2 = 32%). Conclusions. This is the first study to define normal levels of the calcification inhibitors in children and show that fetuin-A and OPG are associated with increased vascular stiffness and calcification in children on dialysis. Higher levels of fetuin-A in children suggest a possible protective upregulation of fetuin-A in the early stages of exposure to the pro-calcific and pro-inflammatory uraemic environment

Original language	English
Pages (from-to)	3263 - 3271
Number of pages	9
Journal	Nephrology, Dialysis, Transplantation
Volume	23
Issue number	10
DOIs	https://doi.org/10.1093/ndt/gfn226
Publication status	Published - Oct 2008

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10.1093/ndt/gfn226

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Shroff, R. C., Shah, V., Hiorns, M. P., Schoppet, M., Hofbauer, L. C., Hawa, G., Schurgers, L. J., Singhal, A., Merryweather, I., Brogan, P., Shanahan, C., Deanfield, J., & Rees, L. (2008). The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis. Nephrology, Dialysis, Transplantation, 23(10), 3263 - 3271. https://doi.org/10.1093/ndt/gfn226

@article{ba1417ea09714f78b9266a2318423bff,

title = "The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis",

abstract = "Background. Vascular calcification occurs in the majority of patients with chronic kidney disease, but a subset of patients does not develop calcification despite exposure to a similar uraemic environment. Physiological inhibitors of calcification, fetuin-A, osteoprotegerin (OPG) and undercarboxylated-matrix Gla protein (uc-MGP) may play a role in preventing the development and progression of ectopic calcification, but there are scarce and conflicting data from clinical studies. Methods. We measured fetuin-A, OPG and uc-MGP in 61 children on dialysis and studied their associations with clinical, biochemical and vascular measures. Results. Fetuin-A and OPG were higher and uc-MGP lower in dialysis patients than controls. In controls, fetuin-A and OPG increased with age. Fetuin-A showed an inverse correlation with dialysis vintage (P = 0.0013), time-averaged serum phosphate (P = 0.03) and hs-CRP (P = 0.001). Aortic pulse wave velocity (PWV) and augmentation index showed a negative correlation with fetuin-A while a positive correlation was seen with PWV and OPG. Patients with calcification had lower fetuin-A and higher OPG than those without calcification. On multiple linear regression analysis Fetuin-A independently predicted aortic PWV (P = 0.004, ss = -0.45, model R-2 = 48%) and fetuin-A and OPG predicted cardiac calcification (P = 0.02, ss = -0.29 and P = 0.014, ss = 0.33, respectively, model R-2 = 32%). Conclusions. This is the first study to define normal levels of the calcification inhibitors in children and show that fetuin-A and OPG are associated with increased vascular stiffness and calcification in children on dialysis. Higher levels of fetuin-A in children suggest a possible protective upregulation of fetuin-A in the early stages of exposure to the pro-calcific and pro-inflammatory uraemic environment",

author = "Shroff, {R C} and V Shah and Hiorns, {M P} and M Schoppet and Hofbauer, {L C} and G Hawa and Schurgers, {L J} and A Singhal and I Merryweather and P Brogan and C Shanahan and J Deanfield and L Rees",

year = "2008",

month = oct,

doi = "10.1093/ndt/gfn226",

language = "English",

volume = "23",

pages = "3263 -- 3271",

journal = "Nephrology, Dialysis, Transplantation",

issn = "1460-2385",

publisher = "Oxford University Press",

number = "10",

}

Shroff, RC, Shah, V, Hiorns, MP, Schoppet, M, Hofbauer, LC, Hawa, G, Schurgers, LJ, Singhal, A, Merryweather, I, Brogan, P, Shanahan, C, Deanfield, J & Rees, L 2008, 'The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis', Nephrology, Dialysis, Transplantation, vol. 23, no. 10, pp. 3263 - 3271. https://doi.org/10.1093/ndt/gfn226

The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis. / Shroff, R C; Shah, V; Hiorns, M P et al.
In: Nephrology, Dialysis, Transplantation, Vol. 23, No. 10, 10.2008, p. 3263 - 3271.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis

AU - Shroff, R C

AU - Shah, V

AU - Hiorns, M P

AU - Schoppet, M

AU - Hofbauer, L C

AU - Hawa, G

AU - Schurgers, L J

AU - Singhal, A

AU - Merryweather, I

AU - Brogan, P

AU - Shanahan, C

AU - Deanfield, J

AU - Rees, L

PY - 2008/10

Y1 - 2008/10

N2 - Background. Vascular calcification occurs in the majority of patients with chronic kidney disease, but a subset of patients does not develop calcification despite exposure to a similar uraemic environment. Physiological inhibitors of calcification, fetuin-A, osteoprotegerin (OPG) and undercarboxylated-matrix Gla protein (uc-MGP) may play a role in preventing the development and progression of ectopic calcification, but there are scarce and conflicting data from clinical studies. Methods. We measured fetuin-A, OPG and uc-MGP in 61 children on dialysis and studied their associations with clinical, biochemical and vascular measures. Results. Fetuin-A and OPG were higher and uc-MGP lower in dialysis patients than controls. In controls, fetuin-A and OPG increased with age. Fetuin-A showed an inverse correlation with dialysis vintage (P = 0.0013), time-averaged serum phosphate (P = 0.03) and hs-CRP (P = 0.001). Aortic pulse wave velocity (PWV) and augmentation index showed a negative correlation with fetuin-A while a positive correlation was seen with PWV and OPG. Patients with calcification had lower fetuin-A and higher OPG than those without calcification. On multiple linear regression analysis Fetuin-A independently predicted aortic PWV (P = 0.004, ss = -0.45, model R-2 = 48%) and fetuin-A and OPG predicted cardiac calcification (P = 0.02, ss = -0.29 and P = 0.014, ss = 0.33, respectively, model R-2 = 32%). Conclusions. This is the first study to define normal levels of the calcification inhibitors in children and show that fetuin-A and OPG are associated with increased vascular stiffness and calcification in children on dialysis. Higher levels of fetuin-A in children suggest a possible protective upregulation of fetuin-A in the early stages of exposure to the pro-calcific and pro-inflammatory uraemic environment

AB - Background. Vascular calcification occurs in the majority of patients with chronic kidney disease, but a subset of patients does not develop calcification despite exposure to a similar uraemic environment. Physiological inhibitors of calcification, fetuin-A, osteoprotegerin (OPG) and undercarboxylated-matrix Gla protein (uc-MGP) may play a role in preventing the development and progression of ectopic calcification, but there are scarce and conflicting data from clinical studies. Methods. We measured fetuin-A, OPG and uc-MGP in 61 children on dialysis and studied their associations with clinical, biochemical and vascular measures. Results. Fetuin-A and OPG were higher and uc-MGP lower in dialysis patients than controls. In controls, fetuin-A and OPG increased with age. Fetuin-A showed an inverse correlation with dialysis vintage (P = 0.0013), time-averaged serum phosphate (P = 0.03) and hs-CRP (P = 0.001). Aortic pulse wave velocity (PWV) and augmentation index showed a negative correlation with fetuin-A while a positive correlation was seen with PWV and OPG. Patients with calcification had lower fetuin-A and higher OPG than those without calcification. On multiple linear regression analysis Fetuin-A independently predicted aortic PWV (P = 0.004, ss = -0.45, model R-2 = 48%) and fetuin-A and OPG predicted cardiac calcification (P = 0.02, ss = -0.29 and P = 0.014, ss = 0.33, respectively, model R-2 = 32%). Conclusions. This is the first study to define normal levels of the calcification inhibitors in children and show that fetuin-A and OPG are associated with increased vascular stiffness and calcification in children on dialysis. Higher levels of fetuin-A in children suggest a possible protective upregulation of fetuin-A in the early stages of exposure to the pro-calcific and pro-inflammatory uraemic environment

U2 - 10.1093/ndt/gfn226

DO - 10.1093/ndt/gfn226

M3 - Article

SN - 1460-2385

VL - 23

SP - 3263

EP - 3271

JO - Nephrology, Dialysis, Transplantation

JF - Nephrology, Dialysis, Transplantation

IS - 10

ER -

The circulating calcification inhibitors, fetuin-A and osteoprotegerin, but not Matrix Gla protein, are associated with vascular stiffness and calcification in children on dialysis

Abstract

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