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.
Highlights
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 (FGF23) 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
There were 104 patients, consisting of 75 females and 29 males with mean age of 59 (± 15) years. 22 patients were in CKD stage 2, 29 patients in CKD stage 3, 19 patients in stages 4 or 5, and 34 patients on maintenance hemodialysis (CKD 5D)
Summary
Renal osteodystrophy (ROD) develops early in chronic kidney disease (CKD) and progresses with loss of kidney function. Renal osteodystrophy (ROD) represents the bone manifestation of CKD-MBD; it starts in patients as early as CKD stage 2 and progresses with further loss of kidney function [7, 8]. Progressive loss of kidney function is associated with an increase in intact parathyroid hormone (PTH), serum phosphorus, fibroblast growth factor-23 (FGF-23), and a decrease in 1,25-dihydroxyvitamin D3 (1,25D). These abnormalities are considered to be the main pathologic factors for renal osteodystrophy [7, 9, 10], but they are not sufficient to explain the bone changes that may occur as early as stage 2 [7, 11]. Identification of novel factors, especially in the early stages of CKD, is important for a more complete understanding of the pathogenesis of ROD
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