Parathyroid Klotho Expression Declines with Renal Function in Hyperparathyroid CKD Patients
(English)Manuscript (preprint) (Other academic)
Current data suggest that type I membrane-bound α-Klotho plays a dual role in the regulation of PTH secretion. While stimulating PTH release during hypocalcemia, Klotho inhibits PTH production by mediating the suppressive effect of fibroblast growth factor-23 (FGF23). In chronic kidney disease (CKD), secondary hyperparathyroidism (sHPT) often develops in the presence of high serum FGF23, indicating parathyroid resistance to FGF23 action. This could in part be due to reduced Klotho expression, as reported in kidneys of CKD patients. Herein, we analyzed parathyroid Klotho expression level in 31 patients with sHPT as well as regulation of Klotho in isolated bovine parathyroid cells using real-time PCR analysis and IHC staining. Klotho expression was variable in secondary hyperplastic glands, yet the mRNA levels correlated positively with glomerular filtration rate and significantly decreased over CKD stages. In vitro treatment with either FGF23 or calcium dose-dependently reduced the Klotho level, whereas vitamin D treatment increased its expression. This stimulatory effect was blunted in the presence of either high FGF23 or calcium. No effect on Klotho level was observed after treatment with phosphate or PTH. In summary, parathyroid Klotho expression was variable in sHPT but decreased with declining renal function. This may be due to a complex co-regulation by calcium, FGF23 and vitamin D, and explain the lack of suppressive effects of FGF23 on PTH secretion in late CKD.
Klotho, CKD, chronic kidney disease, fibroblast growth factor-23, FGF23, phosphate, sHPT, secondary hyperparathyroidism, vitamin D
Endocrinology and Diabetes
Research subject Internal Medicine
IdentifiersURN: urn:nbn:se:uu:diva-107450OAI: oai:DiVA.org:uu-107450DiVA: diva2:229415
*These authors contributed equally.2009-08-122009-08-122010-01-14