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


METHODS
This was a prospective, single-arm trial conducted at Tokai University School of Medicine.


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


METHODS
All patients underwent total PTx with forearm autotransplantation.


METHODS
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.
Division of Nephrology, Endocrinology, and Metabolism (H.T., H.K., K.S., R.T., G.K., T.K., M.F.), Tokai University School of Medicine, Isehara 259-1193, Japan; Jinken Clinic (Y.T.), Ebina 243-0432, Japan; and Division of Nephrology and Diabetes (H.S.), Tokai University Oiso Hospital, Oiso 259-0198, Japan.
Hiroo
H
Takahashi
Hirotaka
H
Komaba
Yuichiro
Y
Takahashi
Kaichiro
K
Sawada
Ryoko
R
Tatsumi
Genta
G
Kanai
Hajime
H
Suzuki
Takatoshi
T
Kakuta
Masafumi
M
Fukagawa
D000368:Aged; D000069449:Cinacalcet; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood* / Q000209:etiology / Q000601:surgery*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use; D016105:Parathyroidectomy; D011184:Postoperative Period; D006435:Renal Dialysis; D012720:Severity of Illness Index; D012995:Solubility
C000717427:FGF23 protein, human; D009281:Naphthalenes; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D000069449:Cinacalcet