Interactions of sclerostin with FGF23, soluble klotho and vitamin D in renal transplantation

Relationships of Sclerostin, a bone anti-anabolic protein, with biomarkers of mineral bone disorders in chronic kidney disease are still unsettled, in particular in kidney transplant (KTR). In 80 KTR patients (31F/49M, 54.7±10.3 years) we studied the relationships of serum Sclerostin with eGFR, Calcium, Phosphate, Alkaline Phosphatase (AP), intact Parathyroid hormone (iPTH), soluble alpha-Klotho (sKlotho), intact Fibroblast Growth Factor 23 (iFGF23), 25-hydroxyvitamin D(25D) and 1,25-dihydroxyvitamin D (1,25D). Thirty healthy subjects (35.0±12.4 years, eGFR 109.1±14.1 ml /min/1,73m2) served as control for Sclerostin, iFGF23 and sKlotho. With a median eGFR of 46.3 mL/min/1.73m2 (IQR, 36.2-58.3) our KTR had median Sclerostin levels of 23.7 pmol/L (IQR: 20.8-32.8), not different from controls (26.6 pmol/L, IQR: 22.0-32.2; p = n.s). Sclerostin correlated negatively with AP (r = -.251; p = 0.023) and positively with iFGF23 (r = .227; p = 0.017) and 25D (r = .214; p = 0.025). Age-adjusted multiple regression analysis identified AP and 1,25D as negative and 25D and sKlotho as positive best predictors of Sclerostin. No correlation was evident with eGFR. The negative correlation with AP confirms the direct anti-anabolic role of Sclerostin. The associations either negative or positive with iFGF23, sKlotho, and vitamin D metabolites suggest also a modulatory role in mineral homeostasis. In particular, the associations with iFGF23 (positive) and 1,25D (negative) underline the relevant inhibitory action of Sclerostin on vitamin D activation. In conclusion, Sclerostin levels in KTR are normal and influenced more by bone turnover than by eGFR. Its involvement with other hormones of mineral homeostasis (FGF23/Klotho and Vitamin D) is part of the sophisticated cross-talk between bone and the kidney.