Serum bone markers in ROD patients across the spectrum of decreases in GFR: Activin A increases before all other markers

Florence Lima, Hanna Mawad, Amr A. El-Husseini, Daniel L. Davenport, Hartmut H. Malluche

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Introduction: Renal osteodystrophy (ROD) develops early in chronic kidney disease (CKD) and progresses with loss of kidney function. While intact parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3 (1,25D), and fibroblast growth factor-23 (FGF-23) levels are usually considered the primary abnormalities in ROD development, the role of serum activin A elevations in CKD and its relationships to ROD have not been explored. The aims of this study were to evaluate serum activin A at different CKD stages, and to establish the relationships between activin A, bone biomarkers, and bone histomorphometric parameters. Materials and methods: 104 patients with CKD stages 2 – 5D underwent bone biopsies. We measured in the serum activin A, BSAP, DKK1, FGF-23, α-Klotho, intact PTH, sclerostin, TRAP-5b, and 1,25D. Biochemical results were compared across CKD stages and with 19 age-matched controls with normal kidney function. Results: Median activin A levels were increased in all stages of CKD compared to controls from 544 pg/ mL in CKD 2 (431 – 628) to 1,135 pg/mL in CKD 5D (816 – 1,456), compared to 369 pg/mL in controls (316 – 453, p < 0.01). The increase of activin A in CKD 2 (p = 0.016) occurred before changes in the other measured biomarkers. Activin A correlated with intact PTH and FGF-23 (r = 0.65 and 0.61; p < 0.01) and with histomorphometric parameters of bone turnover (BFR/BS, Acf, ObS/ BS and OcS/BS; r = 0.47 – 0.52; p < 0.01). These correlations were comparable to those found with intact PTH and FGF-23. Conclusion: Serum activin A levels increase starting at CKD 2 before elevations in intact PTH and FGF-23. Activin A correlates with bone turnover similar to intact PTH and FGF-23. These findings suggest a role for activin A in early development of ROD.

Original languageEnglish
Pages (from-to)222-230
Number of pages9
JournalClinical Nephrology
Volume91
Issue number4
DOIs
StatePublished - 2019

Bibliographical note

Funding Information:
This study was funded in part by the National Institutes of Health, Grant RO1 080770, UK Center for Clinical and Translational Science (CCTS), and the Kentucky Nephrology Research Trust (KNRT).

Publisher Copyright:
© 2019 Dustri-Verlag Dr. Karl Feistle. All rights reserved.

Keywords

  • Activin A
  • Bone turnover
  • CKD-MBD
  • Renal osteodystrophy

ASJC Scopus subject areas

  • Medicine (all)

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