Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis

Stuart M. Sprague, Ezequiel Bellorin-Font, Vanda Jorgetti, Aluizio B. Carvalho, Hartmut H. Malluche, Aníbal Ferreira, Patrick C. D'Haese, Tilman B. Drüeke, Hongyan Du, Thomas Manley, Eudocia Rojas, Sharon M. Moe

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83 Scopus citations

Abstract

Background: The management of chronic kidney disease-mineral and bone disorder requires the assessment of bone turnover, which most often is based on parathyroid hormone (PTH) concentration, the utility of which remains controversial. Study Design: Cross-sectional retrospective diagnostic test study. Setting & Participants: 492 dialysis patients from Brazil, Portugal, Turkey, and Venezuela with prior bone biopsy and stored (-20°C) serum. Index Tests: Samples were analyzed for PTH (intact [iPTH] and whole PTH), bone-specific alkaline phosphatase (bALP), and amino-terminal propeptide of type 1 procollagen (P1NP). Reference Test: Bone histomorphometric assessment of turnover (bone formation rate/bone surface [BFR/BS]) and receiver operating characteristic curves for discriminating diagnostic ability. Results: The biomarkers iPTH and bALP or combinations thereof allowed discrimination of low from nonlow and high from nonhigh BFR/BS, with an area under the receiver operating characteristic curve > 0.70 but<0.80. Using iPTH level, the best cutoff to discriminate low from nonlow BFR/BS was<103.8. pg/mL, and to discriminate high from nonhigh BFR/BS was >323.0. pg/mL. The best cutoff for bALP to discriminate low from nonlow BFR/BS was<33.1. U/L, and for high from nonhigh BFR/BS, 42.1. U/L. Using the KDIGO practice guideline PTH values of greater than 2 but less than 9 times the upper limit of normal, sensitivity and specificity of iPTH level to discriminate low from nonlow turnover bone disease were 65.7% and 65.3%, and to discriminate high from nonhigh were 37.0% and 85.8%, respectively. Limitations: Cross-sectional design without consideration of therapy. Potential limited generalizability with samples from 4 countries. Conclusions: The serum biomarkers iPTH, whole PTH, and bALP were able to discriminate low from nonlow BFR/BS, whereas iPTH and bALP were able to discriminate high from nonhigh BFR/BS. Prospective studies are required to determine whether evaluating trends in biomarker concentrations could guide therapeutic decisions.

Original languageEnglish (US)
Pages (from-to)559-566
Number of pages8
JournalAmerican Journal of Kidney Diseases
Volume67
Issue number4
DOIs
StatePublished - Apr 1 2016

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Keywords

  • Alkaline phosphatases
  • Bone histomorphometry
  • Bone-specific alkaline phosphatase (bALP
  • BSAP)
  • Chronic kidney disease-mineral bone disorder (CKD-MBD)
  • Parathyroid hormone (PTH)
  • Procollagen type 1 N propeptide (P1NP)
  • Renal osteodystrophy
  • Sensitivity and specificity

ASJC Scopus subject areas

  • Nephrology

Cite this

Sprague, S. M., Bellorin-Font, E., Jorgetti, V., Carvalho, A. B., Malluche, H. H., Ferreira, A., D'Haese, P. C., Drüeke, T. B., Du, H., Manley, T., Rojas, E., & Moe, S. M. (2016). Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis. American Journal of Kidney Diseases, 67(4), 559-566. https://doi.org/10.1053/j.ajkd.2015.06.023