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

doi:10.1053/j.ajkd.2015.06.023

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

Internal Medicine

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

223 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 language	English
Pages (from-to)	559-566
Number of pages	8
Journal	American Journal of Kidney Diseases
Volume	67
Issue number	4
DOIs	https://doi.org/10.1053/j.ajkd.2015.06.023
State	Published - Apr 1 2016

Bibliographical note

Publisher Copyright:
© 2016 National Kidney Foundation, Inc.

Funding

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. 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.

Funders	Funder number
DiaSorin Corporation
Fresenius Medical Care, Sanofi/Genzyme
KDIGO
Vifor Pharma Management
Abbott Laboratories
AMGen
Genzyme Corporation
Novartis
Baxter International
Sanofi Genzyme
Fresenius Medical Care North America
National Kidney Foundation
Shire

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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10.1053/j.ajkd.2015.06.023

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

@article{cabc0a19416d47de982e1ebaba961da6,

title = "Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis",

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.",

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",

author = "Sprague, {Stuart M.} and Ezequiel Bellorin-Font and Vanda Jorgetti and Carvalho, {Aluizio B.} and Malluche, {Hartmut H.} and An{\'i}bal Ferreira and D'Haese, {Patrick C.} and Dr{\"u}eke, {Tilman B.} and Hongyan Du and Thomas Manley and Eudocia Rojas and Moe, {Sharon M.}",

note = "Publisher Copyright: {\textcopyright} 2016 National Kidney Foundation, Inc.",

year = "2016",

month = apr,

day = "1",

doi = "10.1053/j.ajkd.2015.06.023",

language = "English",

volume = "67",

pages = "559--566",

number = "4",

}

Sprague, SM, Bellorin-Font, E, Jorgetti, V, Carvalho, AB, Malluche, HH, Ferreira, A, D'Haese, PC, Drüeke, TB, Du, H, Manley, T, Rojas, E & Moe, SM 2016, 'Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis', American Journal of Kidney Diseases, vol. 67, no. 4, pp. 559-566. https://doi.org/10.1053/j.ajkd.2015.06.023

TY - JOUR

T1 - Diagnostic accuracy of bone turnover markers and bone histology in patients with CKD treated by dialysis

AU - Sprague, Stuart M.

AU - Bellorin-Font, Ezequiel

AU - Jorgetti, Vanda

AU - Carvalho, Aluizio B.

AU - Malluche, Hartmut H.

AU - Ferreira, Aníbal

AU - D'Haese, Patrick C.

AU - Drüeke, Tilman B.

AU - Du, Hongyan

AU - Manley, Thomas

AU - Rojas, Eudocia

AU - Moe, Sharon M.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - BSAP)

KW - Sensitivity and specificity

KW - alkaline phosphatases

KW - bone histomorphometry

KW - bone-specific alkaline phosphatase (bALP

KW - chronic kidney disease-mineral bone disorder (CKD-MBD)

KW - parathyroid hormone (PTH)

KW - procollagen type 1 N propeptide (P1NP)

KW - renal osteodystrophy

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DO - 10.1053/j.ajkd.2015.06.023

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AN - SCOPUS:84940093320

SN - 0272-6386

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EP - 566

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

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ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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