Impact of parathyroidectomy on serum FGF23 and soluble Klotho in hemodialysis patients with severe secondary hyperparathyroidism.

Context: Klotho is a transmembrane protein that functions as a coreceptor for fibroblast growth factor 23 (FGF23). Klotho is cleaved and released into the circulation; however, the main site of production, physiological role, and regulation of soluble Klotho in humans are largely unknown.

Objective: The aim of this study was to determine the impact of parathyroidectomy (PTx) on serum FGF23 and soluble Klotho levels in patients with severe secondary hyperparathyroidism.

Design And Setting: This was a prospective, single-arm trial conducted at Tokai University School of Medicine.

Patients: Thirteen hemodialysis patients with severe secondary hyperparathyroidism who were candidates for PTx participated in the study.

Interventions: All patients underwent total PTx with forearm autotransplantation.

Main Outcome Measures: We evaluated changes in serum FGF23 and soluble Klotho levels for 90 days after PTx. Other biochemical parameters related to mineral and bone metabolism were also assessed.

Results: At baseline, serum FGF23 levels were markedly elevated, whereas serum soluble Klotho levels were modestly decreased. PTx resulted in a marked, progressive decline in serum FGF23 levels together with significant reductions in serum calcium, phosphorus, and intact PTH levels. The serum soluble Klotho levels were reduced 13% from baseline on the day after PTx; however, these levels then increased progressively, reaching 34% above the postoperative values.

Conclusions: Our results suggest that the parathyroid gland is not the major site of soluble Klotho production in patients with end-stage renal disease, and the production of Klotho by other organ(s) is affected by alterations in mineral metabolism or medications taken after PTx.