Parathyroid Klotho and FGF-receptor 1 expression decline with renal function in hyperparathyroid patients with

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Tijana Krajisnik1, Hannes Olauson, Majd A I Mirza

  • 1Department of Medical Sciences, Uppsala University, Uppsala, Sweden. Tijana.Krajisnik@medsci.uu.se

Kidney International
|August 6, 2010
PubMed

Insights

Parathyroid glands show decreased fibroblast growth factor 23 (FGF23) receptors, Klotho and FGF receptor 1 (FGFR1), with worsening chronic kidney disease (CKD). This FGF23 resistance may explain secondary hyperparathyroidism in CKD patients.

Area of Science:

  • Endocrinology
  • Nephrology
  • Molecular Biology

Background:

  • Fibroblast growth factor 23 (FGF23) normally inhibits parathyroid hormone secretion.
  • Patients with chronic kidney disease (CKD) paradoxically develop secondary hyperparathyroidism despite elevated FGF23 levels, suggesting FGF23 resistance in parathyroid glands.

Purpose of the Study:

  • To investigate the expression and regulation of FGF23 receptors, Klotho and FGF receptor 1 (FGFR1), in parathyroid glands of patients with CKD.
  • To explore the potential mechanisms underlying parathyroid FGF23 resistance in CKD.

Main Methods:

  • Analysis of Klotho and FGFR1 mRNA expression in 88 hyperplastic parathyroid glands from 31 CKD patients.
  • In vitro studies using isolated bovine and human hyperplastic parathyroid cells treated with FGF23, calcium, vitamin D, phosphate, and parathyroid hormone.

Main Results:

  • Klotho and FGFR1 mRNA levels in parathyroid glands significantly decreased with declining glomerular filtration rate across CKD stages.
  • In vitro, FGF23 and calcium reduced Klotho expression in bovine cells, while vitamin D increased it.
  • FGFR1 expression was induced in human hyperplastic cells, and Klotho regulation differed between bovine and human cells.

Conclusions:

  • Parathyroid Klotho and FGFR1 expression decline with worsening renal function in CKD.
  • Altered mineral metabolism in CKD may contribute to decreased FGF23 receptor expression.
  • Reduced parathyroid Klotho and FGFR1 expression likely underlies FGF23 resistance observed in advanced CKD.

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