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. 2010 Jul;5(7):1268-76.
doi: 10.2215/CJN.08241109. Epub 2010 May 6.

Fibroblast growth factor-23 in early chronic kidney disease: additional support in favor of a phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism

Pieter Evenepoel  1 , Björn Meijers, Liesbeth Viaene, Bert Bammens, Kathleen Claes, Dirk Kuypers, Dirk Vanderschueren, Yves Vanrenterghem
Affiliations

Fibroblast growth factor-23 in early chronic kidney disease: additional support in favor of a phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism

Pieter Evenepoel et al. Clin J Am Soc Nephrol. 2010 Jul.

Abstract

Background and objectives: The discovery of fibroblast growth factor-23 (FGF-23) and the elucidation of its function as a phosphaturic and 1,25(OH)2VitD counter-regulatory hormone provides a new conceptual framework for the understanding of the pathogenesis of secondary hyperparathyroidism. This study aims to elucidate the complex associations between FGF-23, parathyroid hormone (PTH), 1,25(OH)2D, and phosphate in patients with early-stage chronic kidney disease (CKD) and to provide clinical evidence in favor of the new phosphate-centric paradigm for the pathogenesis of secondary hyperparathyroidism.

Design, setting, participants, & measurements: Serum biointact PTH and FGF-23, 25(OH)D, 1,25(OH)2D, calcium, phosphate, 24-hour urine excretion of phosphate and calcium, and urinary fractional excretion of phosphate were determined in a cross-sectional study including 125 patients with CKD stages 1 to 3.

Results: Serum phosphate levels showed an inverse association with estimated GFR (eGFR), but were within the normal range in all but one patient. FGF-23 and PTH were inversely associated with eGFR, even in the subgroup of patients with CKD stages 1 and 2. High FGF-23 levels were significantly more prevalent than high PTH levels. The urinary fractional excretion of phosphate was highest in patients with both a high serum FGF-23 and PTH level. Increased FGF-23 and phosphate and decreased 25(OH)D were independently associated with decreased 1,25(OH)2D.

Conclusions: Our data are in favor of the new paradigm for the pathogenesis of secondary hyperparathyroidism according to which a reduced phosphate excretion capacity is the principal abnormality that initiates secondary hyperparathyroidism.

Trial registration: ClinicalTrials.gov NCT00441623.

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Figures

Figure 1.
Figure 1.
Phosphate (A), PTH (B), FGF-23 (C), and calcitriol (D) levels according to eGFR. Dashed line denotes the upper normal limit.
Figure 2.
Figure 2.
Fractional excretion of phosphate according to eGFR (A) and categorized according to serum FGF-23 and PTH level (high denotes >40 ng/L for PTH and >50 pg/ml for FGF-23) (B).
See this image and copyright information in PMC

References

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