Biomarkers of vascular calcification and mortality in patients with ESRD

Julia J. Scialla, W. H Linda Kao, Ciprian Crainiceanu, Stephen M. Sozio, Pooja C. Oberai, Tariq Shafi, Josef Coresh, Neil R. Powe, Laura C. Plantinga, Bernard G. Jaar, Rulan S. Parekh

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

BACKGROUND: Vascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: OPG, OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident dialysis patients recruited from United States dialysis centers between 1995 and 1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their association with all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts.

RESULTS: Higher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95% confidence interval [95% CI], 1.08 to 2.06) for OPG and 0.69 (95% CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients without diabetes (HR, 2.42; 95% CI, 1.35 to 4.34), but not patients with diabetes (HR, 1.26; 95% CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L: 95% CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated with greater risk (HR for highest versus lowest tertile, 2.91; 95% CI, 1.06 to 7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not independently associated with outcomes overall. The addition of OPG and fetuin-A did not significantly improve predictive accuracy of mortality.

CONCLUSIONS: OPG and fetuin-A may be risk factors for all-cause and cardiovascular mortality in patients undergoing dialysis, but do not improve risk prediction.

Original languageEnglish
Pages (from-to)745-755
Number of pages11
JournalClinical journal of the American Society of Nephrology : CJASN
Volume9
Issue number4
DOIs
StatePublished - Apr 1 2014

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Vascular Calcification
alpha-2-HS-Glycoprotein
Osteoprotegerin
Chronic Kidney Failure
Biomarkers
Mortality
Confidence Intervals
Osteopontin
Dialysis
Bone and Bones
Odds Ratio
Proteins
Proportional Hazards Models
Comorbidity
Demography

Keywords

  • diabetes
  • end-stage renal disease
  • vascular calcification

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Scialla, J. J., Kao, W. H. L., Crainiceanu, C., Sozio, S. M., Oberai, P. C., Shafi, T., ... Parekh, R. S. (2014). Biomarkers of vascular calcification and mortality in patients with ESRD. Clinical journal of the American Society of Nephrology : CJASN, 9(4), 745-755. https://doi.org/10.2215/CJN.05450513

Biomarkers of vascular calcification and mortality in patients with ESRD. / Scialla, Julia J.; Kao, W. H Linda; Crainiceanu, Ciprian; Sozio, Stephen M.; Oberai, Pooja C.; Shafi, Tariq; Coresh, Josef; Powe, Neil R.; Plantinga, Laura C.; Jaar, Bernard G.; Parekh, Rulan S.

In: Clinical journal of the American Society of Nephrology : CJASN, Vol. 9, No. 4, 01.04.2014, p. 745-755.

Research output: Contribution to journalArticle

Scialla, JJ, Kao, WHL, Crainiceanu, C, Sozio, SM, Oberai, PC, Shafi, T, Coresh, J, Powe, NR, Plantinga, LC, Jaar, BG & Parekh, RS 2014, 'Biomarkers of vascular calcification and mortality in patients with ESRD', Clinical journal of the American Society of Nephrology : CJASN, vol. 9, no. 4, pp. 745-755. https://doi.org/10.2215/CJN.05450513
Scialla, Julia J. ; Kao, W. H Linda ; Crainiceanu, Ciprian ; Sozio, Stephen M. ; Oberai, Pooja C. ; Shafi, Tariq ; Coresh, Josef ; Powe, Neil R. ; Plantinga, Laura C. ; Jaar, Bernard G. ; Parekh, Rulan S. / Biomarkers of vascular calcification and mortality in patients with ESRD. In: Clinical journal of the American Society of Nephrology : CJASN. 2014 ; Vol. 9, No. 4. pp. 745-755.
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abstract = "BACKGROUND: Vascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: OPG, OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident dialysis patients recruited from United States dialysis centers between 1995 and 1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their association with all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts.RESULTS: Higher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95{\%} confidence interval [95{\%} CI], 1.08 to 2.06) for OPG and 0.69 (95{\%} CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients without diabetes (HR, 2.42; 95{\%} CI, 1.35 to 4.34), but not patients with diabetes (HR, 1.26; 95{\%} CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L: 95{\%} CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated with greater risk (HR for highest versus lowest tertile, 2.91; 95{\%} CI, 1.06 to 7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not independently associated with outcomes overall. The addition of OPG and fetuin-A did not significantly improve predictive accuracy of mortality.CONCLUSIONS: OPG and fetuin-A may be risk factors for all-cause and cardiovascular mortality in patients undergoing dialysis, but do not improve risk prediction.",
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AU - Scialla, Julia J.

AU - Kao, W. H Linda

AU - Crainiceanu, Ciprian

AU - Sozio, Stephen M.

AU - Oberai, Pooja C.

AU - Shafi, Tariq

AU - Coresh, Josef

AU - Powe, Neil R.

AU - Plantinga, Laura C.

AU - Jaar, Bernard G.

AU - Parekh, Rulan S.

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N2 - BACKGROUND: Vascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: OPG, OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident dialysis patients recruited from United States dialysis centers between 1995 and 1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their association with all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts.RESULTS: Higher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95% confidence interval [95% CI], 1.08 to 2.06) for OPG and 0.69 (95% CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients without diabetes (HR, 2.42; 95% CI, 1.35 to 4.34), but not patients with diabetes (HR, 1.26; 95% CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L: 95% CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated with greater risk (HR for highest versus lowest tertile, 2.91; 95% CI, 1.06 to 7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not independently associated with outcomes overall. The addition of OPG and fetuin-A did not significantly improve predictive accuracy of mortality.CONCLUSIONS: OPG and fetuin-A may be risk factors for all-cause and cardiovascular mortality in patients undergoing dialysis, but do not improve risk prediction.

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KW - end-stage renal disease

KW - vascular calcification

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