Variations of parathyroid hormone and bone biomarkers are concordant only after a long term follow-up in hemodialyzed patients

Pierre Delanaye,Hans Pottel,Nicole Smelten,Etienne Cavalier,Xavier Warling,Martial Moonen,Jean-Marie Krzesinski,François Jouret,Nicolas Maillard,Nicolas Maillard

doi:10.1038/s41598-017-12808-3

Abstract

End-stage renal disease is associated with mineral and bone disorders. Guidelines recommending therapies should be based on serial assessments of biomarkers, and thus on variations (Δ), rather than scattered values. We analyzed the correlations between ΔPTH and Δbone biomarkers such as bone-specific alkaline phosphatase (b-ALP), Beta-CrossLaps (CTX), osteocalcin, intact serum procollagen type-1 N-propeptide (P1NP), and tartrate-resistant acid phosphatase 5B (TRAP-5B) at different time-points. In this prospective observational analysis, variations of biomarkers were followed after 6-week (n = 129), 6-month (n = 108) and one-year (n = 93) period. Associations between variations were studied by univariate linear regression. Patients followed for one-year period were classified (increaser or decliner) according to variations reaching the critical difference. Over the 6-week period, only ΔCTX was correlated with ΔPTH (r = 0.38, p < 0.0001). Over the one-year period, correlations between ΔPTH and Δbone biomarkers became significant (r from 0.23 to 0.47, p < 0.01), except with ΔTRAP-5b. Correlations between Δbone biomarkers were all significant after one-year period (r from 0.31 to 0.68, p < 0.01), except between Δb-ALP and ΔTRAP-5b. In the head-to-head classifications (decliners/increasers), the percentage of concordant patients was significantly higher over the one-year than the 6-week period. A concordance between ΔPTH and Δbone biomarkers is observed in dialysis patients, but only after a long follow-up.

Highlights

Chronic Kidney Disease (CKD) is associated with mineral and bone disorders (MBD)
We suggested that the correlations between variations of parathyroid hormone (PTH) (ΔPTH) and bone-specific alkaline phosphatase (b-ALP) (Δb-ALP) were poor[11]
Cross-sectional studies showed that the performance of PTH, bone biomarkers or even combinations of both is poor to predict the turnover determined by bone biopsy[3,12,13,14]

Summary

Introduction

Chronic Kidney Disease (CKD) is associated with mineral and bone disorders (MBD). If bone health includes important concepts such as bone mineralization and bone volume, abnormalities in bone turnover remain key and specific to the dialysis population[1]. The gold standard for bone turnover diagnosis is bone biopsy[2]. In cross-sectional studies, a good correlation is found between the two biomarkers[3,9,10,11] Their performance to predict bone turnover assessed by bone biopsies in transversal studies remains disappointing[3,12,13,14]. For this reason, the revised 2017 KDIGO guidelines suggest that potential CKD-MBD therapies should be based on serial assessments of biomarkers, and on trends or variations (Δ), more than on one-single transversal result. The current work, we prospectively followed variations of PTH and other bone biomarkers on a 6-week, 6-month and one-year period

Methods

Results

Conclusion