Effects of cinacalcet treatment on serum soluble Klotho levels in haemodialysis patients with secondary hyperparathyroidism.

Abstract

Klotho is a transmembrane protein that acts as a cofactor for fibroblast growth factor 23 (FGF23). Klotho also exists as a soluble circulating protein, but its role in secondary hyperparathyroidism (SHPT) is largely unknown. We measured serum soluble Klotho levels in 51 haemodialysis patients, who participated and completed a 52-week, multicentre, open-label single-arm trial that examined the effectiveness of cinacalcet for treating SHPT. After 12 weeks of cinacalcet treatment, serum soluble Klotho decreased significantly (P = 0.03) but only marginally from 398 pg/mL [interquartile range (IQR), 268-588 pg/mL] to 378 pg/mL (IQR, 266-568 pg/mL) and returned to baseline levels. There were no significant associations between the changes in soluble Klotho levels and changes in any other parameters of mineral metabolism, including serum calcium, phosphorus, intact parathyroid hormone and FGF23. Despite significant alterations in mineral and bone metabolism during treatment with cinacalcet, this resulted in only small and transient reductions in serum levels of soluble Klotho.