Circulating Levels of Soluble α-Klotho Are Markedly Elevated in Human Umbilical Cord Blood

Context: Fetal serum levels of calcium and phosphate are higher than those in the maternal levels. Although alpha-Klotho is known to participate in calcium and phosphate metabolism in adults, its role in the perinatal period remains unknown. Objective: This study aimed to determine the baseline levels of soluble alpha-Klotho in fetuses and compare them with those in neonates, mothers, and adults to clarify whether alpha-Klotho is involved in the fetal-specific regulation of calcium and phosphate metabolism. Design and Setting: We conducted a cross-sectional evaluation of healthy babies (at birth and/or at 4 d after birth), their mothers, and adult volunteers at one hospital. Participants: Twenty-one healthy mothers, their babies (23 in total, including two pairs of twins), and 25 adult volunteers participated in the study. Main Outcome Measures: We measured the serum levels of soluble alpha-Klotho and fibroblast growth factor 23 (FGF23). Results: In cord blood, the level of alpha-Klotho was markedly higher (3243 +/- 1899 pg/ml) than levels in neonates at d 4 (582 +/- 90 pg/ml), mothers (768 +/- 261 pg/ml), and adult volunteers (681 +/- 140 pg/ml) (P < 0.001), whereas the fetal level of FGF23 was lower than levels in the other subjects. The levels of soluble alpha-Klotho were negatively correlated with those of FGF23 in cord blood. Immunohistochemistry demonstrated that alpha-Klotho was predominantly expressed in syncytiotrophoblasts in normal term placenta. Conclusion: Levels of soluble alpha-Klotho are markedly elevated in cord blood and might be useful as a biomarker for mineral metabolism in the fetus. (J Clin Endocrinol Metab 96: E943-E947, 2011)