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

Research output: Contribution to journalArticlepeer-review

168 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
Pages (from-to)559-566
Number of pages8
JournalAmerican Journal of Kidney Diseases
Volume67
Issue number4
DOIs
StatePublished - Apr 1 2016

Bibliographical note

Funding Information:
Financial Disclosure: Dr Sprague has received funding from Abbott-AbbVie, Amgen, Cytochroma, Fresenius Medical Care, and Vifor and consulting fees from Amgen, Cytochroma, and Vifor. Dr Bellorin-Font has received honoraria from Abbott, Amgen, and Sanofi/Genzyme. Dr Jorgetti has received consulting and speaker fees from Abbott, Amgen, and Sanofi/Genzyme. Dr Carvalho has received consulting and speaker fees from Abbott-Abbvie, Amgen, and Sanofi/Genzyme. Dr Malluche has received research support from Novartis , Celgene , and Vifor . Dr Ferreira has received consulting fees from Abbott-Abbvie, Amgen, Fresenius Medical Care, and Sanofi/Genzyme and speaker fees from Abbott-Abbvie, Amgen, Fresenius Medical Care, Sanofi/Genzyme, and Shire. Dr D’Haese has received funding from Amgen, Baxter, Diasorin, Fresenius Medical Care, Novartis, Shire, and Vifor. Dr Drüeke has received consulting fees from Abbott-AbbVie, Amgen, Baxter, Chugai, Fresenius Medical Care, Sanofi/Genzyme, and Vifor; speaker fees from Abbott-AbbVie, Amgen, Chugai, Kirin, Sanofi/Genzyme, and Vifor; and funding from Amgen, Baxter, and Shire. The other authors declare that they have no other relevant financial interests.

Funding Information:
Support: This study was supported by unrestricted grants to the NKF from Abbott , Amgen , Genzyme , and Shire and was facilitated by KDIGO and the NKF, the former managing agent for KDIGO. The funding organizations had no role in the design, conduct, analysis, or interpretation of the study; writing the report; or the decision to submit it for publication.

Publisher Copyright:
© 2016 National Kidney Foundation, Inc.

Keywords

  • BSAP)
  • Sensitivity and specificity
  • alkaline phosphatases
  • bone histomorphometry
  • bone-specific alkaline phosphatase (bALP
  • chronic kidney disease-mineral bone disorder (CKD-MBD)
  • parathyroid hormone (PTH)
  • procollagen type 1 N propeptide (P1NP)
  • renal osteodystrophy

ASJC Scopus subject areas

  • Nephrology

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