Sclerostin declines during hemodialysis and appears in Dialysate.

BACKGROUND/AIMS: Sclerostin, a soluble inhibitor of Wnt-signaling, inhibits bone formation. We assessed the impact of dialysis on serum sclerostin and whether sclerostin is detectable in effluent dialysates. METHODS: In a prospective study of 54 prevalent hemodialysis patients, parameters of bone and mineral metabolism were assessed at the beginning and at the end of dialysis. In a subset of patients (n = 19) sclerostin was measured in serum at start, 1, 2, and 3 h of dialysis and in the effluent dialysate at several points in time. RESULTS: Sclerostin serum levels decreased from median 71.4 pmol/l to 43.5 pmol/l during dialysis (p < 0.0001). In patients with high pre-dialysis sclerostin serum levels, sclerostin was detected in the dialysate. Higher Kt/V correlated with greater relative decrease of sclerostin (r = 0.467; p = 0.001). CONCLUSION: Sclerostin is dialysable. Furthermore, sclerostin serum levels decrease during dialysis. Whether targeting lower sclerostin levels by means of improved dialysis adequacy has direct relevance to bone disease remains to be shown.

Correlations and time course of FGF23 and markers of bone metabolism in maintenance hemodialysis patients.

OBJECTIVE: Parathyroid hormone (iPTH) and fibroblast growth factor 23 (FGF23) are elevated in secondary hyperparathyroidism. In hemodialysis, higher dialysate calcium (1.5 mmol/L) induces intradialytic suppression of iPTH, whereas its impact on FGF23 and markers of bone metabolism is unknown. We assessed the time course of FGF23 and markers of bone metabolism in relationship to dialysate calcium. DESIGN AND METHODS: In this prospective cohort study of 19 patients on maintenance hemodialysis, we measured serum calcium (sCa), inorganic phosphate (iP), blood urea nitrogen (BUN), ß2-microglobulin (ßMG), iPTH, FGF23, aminoterminal propeptide type 1 procollagen (P1NP), C-telopeptide of type I collagen for bone degradation (CTX-I), osteocalcin (OC), bone specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase (TRAP5b) during a single hemodialysis session at baseline, 1, 2, and 3h of dialysis. The time course of measured parameters was compared according to groups of prescribed dialysate calcium of 1.25 mmol/L and 1.5 mmol/L. RESULTS: iPTH declined in the 1.5 mmol/L dialysis group as serum calcium increased whereas it tended to increase in the 1.25 mmol/L group without significant changes in serum calcium. Patients on long-term dialysate calcium of 1.5 mmol/L had significantly lower CTX-I levels and tended to lower levels of iPTH, FGF23, OC, P1NP and TRAP5b at the start of dialysis compared to those on 1.25 mmol/L. CTX-I, FGF23 and OC but not BALP, P1NP and TRAP5b decreased during dialysis independent of dialysate calcium. CONCLUSIONS: In spite of immediate effects on iPTH, dialysate calcium does not acutely affect other parameters of bone and mineral metabolism. SHORT SUMMARY: Dialysate calcium concentration is known to have both immediate and longer-term impact on parathyroid hormone levels in hemodialysis patients. Little is known about the acute impact of dialysate calcium on bone metabolism. In this cross-sectional study of prevalent hemodialysis patients, we found no evidence of immediate short-term dialysate calcium-induced changes of fibroblast growth factor 23 or anabolic and catabolic markers of bone turnover during hemodialysis. However, differences in CTX-I and to a lesser extent other parameters between groups of higher and lower dialysate calcium suggest a longer-term effect that remains to be validated.