Clearance of Sclerostin, Osteocalcin, Fibroblast Growth Factor 23, and Osteoprotegerin by Dialysis

Abstract

Introduction: Fibroblast growth factor (FGF23), sclerostin, osteocalcin, and osteoprotegerin are important factors that control mineral bone metabolism. End-stage renal disease is associated with the pronounced dysregulation of mineral bone metabolism; however, the impact and clearance of mineral bone metabolism factors during dialysis remain largely undescribed. Methods: In a cross-sectional study, 10 chronic hemodialysis patients were treated with hemodialysis for 8 h using a high-flux filter and a dialysate bath of 50% calculated total body water continuously recycled at a rate of 500 mL/min. Plasma and dialysate concentrations of FGF23, sclerostin, osteoprotegerin, and osteocalcin were measured at 1, 2, 4, 6, and 8 h permitting the estimation of dialysis clearance. Results: Clearance of FGF23 was 7.7 mL/min, of sclerostin was 7.6 mL/min, of osteoprotegerin was 1.2 mL/min, and of osteocalcin was 19.7 mL/min. Clearance of FGF23 was correlated to sclerostin and osteoprotegerin clearance and also to the ultrafiltration rate. Although, osteocalcin blood concentrations decreased during dialysis, they rebounded within 6 h. Overall, no significant changes in blood concentrations of the measure mineral bone metabolism factors were observed. Conclusions: The intradialytic clearance of osteocalcin, FGF23, sclerostin, and osteoprotegerin occurs; however, only clearance of FGF23 is directly correlated with the ultrafiltration rate. The effects of dialytic clearance on mineral bone metabolism are, however, uncertain and intradialytic plasma concentrations of the studied substrates remained largely unchanged.

Hemodiafiltration Is Associated With Reduced Inflammation and Increased Bone Formation Compared With Conventional Hemodialysis in Children: The HDF, Hearts and Heights (3H) Study

“…Sclerostin, which is known to be cleared by convective clearance 28 was lower in HDF compared to HD patients even at baseline (p = 0.02), but no change was seen over the 12 month followup in either cohort. There was no difference in CTX in either group at any time point.…”

“…Comparable to previous studies, we showed ~25% lower FGF23 levels in HDF 29 , whereas levels increased by over 100% in HD children. As seen with the dialytic J o u r n a l P r e -p r o o f -11 -clearance of other LMM compounds such as FGF-23, IL-6 and TNF-α, although an early reduction in plasma concentrations is seen with convective clearance 24 , this is not sufficient to further reduce plasma concentrations in the long-term, perhaps as production of these compounds overwhelms the clearance capacity of thrice-weekly dialysis 28 . Although protective in early CKD, FGF23 is known to have several "off-target" effects, independent of changes in mineral metabolism, on cardiac myocytes 47 with an increased prevalence of left ventricular hypertrophy 48 and premature mortality in adults with all stages of CKD 49 , stressing the importance of reducing FGF23 levels by HDF.…”

Sclerostin levels predict cardiovascular mortality in long-term hemodialysis patients: A prospective observational cohort study

“…Additionally, the secondary analysis of the CONTRAST study also demonstrated an association between high sclerostin levels and a lower mortality risk. A study by Carlson et al found that the clearance of sclerostin during hemodialysis occurs at a lower rate but intradialytic plasma levels of substrates involved in bone metabolism including sclerostin remains largely unchanged (Carlson et al 2017). The role of sclerostin as the mediator between bone and vasculature in chronic disease -mineral bone disorder (CKD-MBD) remains a fascinating analytical and clinical area for future further investigations.…”

Cardiotoxicity of Uremic Toxins: A Driver of Cardiorenal Syndrome

“…The off-target detrimental biological activity of FGF23 excess potentially starts early therefore it should be addressed from pre-dialysis CKD. In addition, FGF23 excess of which the levels can be extremely high in patients with end-stage renal disease, may be not easily removed by dialysis even by convection technique [ 96 , 97 ]. This supports the evidence of LVH progression in long-term hemodialysis patients [ 22 , 23 ].…”