Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers
Open accessAbstract
Background Hyperphosphatemia is a risk factor for the development of several different complications of chronic kidney disease (CKD), including secondary hyperparathyroidism and cardiovascular complications, due to the formation of calcium-phosphate deposits. Fibroblast growth factor-23 (FGF-23) is a recently discovered protein that is mutated in autosomal-dominant hypophosphatemic rickets, an inherited phosphate wasting disorder, and it may represent a novel hormonal regulator of phosphate homeostasis. We therefore hypothesized that FGF-23 levels may be altered in hyperphosphatemia associated with renal failure and that its concentration changes in response to different levels of phosphate intake.Methods Using a two-site enzyme-linked immunosorbent assay (ELISA) detecting the C-terminal portion of FGF-23, serum concentration was measured in 20 patients with different stages of renal failure (creatinine range 155 to 724 micromol/L), in 33 patients with end-stage renal disease (ESRD) on dialysis treatment, and in 30 patients with functioning renal grafts. Furthermore, six healthy males were given oral phosphate binders in combination with low dietary phosphate intake for 2 days followed by 3 days of repletion with inorganic phosphate. FGF-23 levels were determined at multiple time points.Results FGF-23 serum levels were significantly elevated in CKD with a strong correlation between serum creatinine and FGF-23 concentration. Independent correlations were also seen between FGF-23 and phosphate, calcium, parathyroid hormone (PTH), and 1,25(OH)2D3. No changes in serum FGF-23 levels were observed in volunteers following ingestion of oral phosphate binders/low dietary phosphate intake, which led to a decline in phosphate excretion or during the subsequent repletion with inorganic phosphate through oral phosphate and a normal diet.Conclusion Circulating FGF-23 was significantly elevated in patients with CKD and its concentration correlated with renal creatinine clearance. In healthy volunteers, FGF-23 levels did not change after phosphate deprivation or phosphate loading.
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Two to five days of high dietary Pi intake increases iFGF23 but not cFGF23.
“Two to five days of high dietary Pi intake increases iFGF23 but not cFGF23 [20, 25, 34, 58].”
From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [34]
Controlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake.
“controlled experiments in healthy humans examined periods of either a few hours or several weeks, and often varied dietary calcium intake.”
From Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels (2025) · cites this paper as [34]
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Controlled dietary phosphate loading in healthy young men elevates plasma phosphate and FGF23 levels
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- Authors
- Larsson, T., Nisbeth, U. L. F., Ljunggren, Ö., Jüppner, H., & Jonsson, K. B.
- Affiliations
- Uppsala University Hospital (SE)
- Harvard University (US)
- Corresponding author
- Jonsson, Kenneth B.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2003-12
- Volume
- 64
- Issue
- 6
- Pages
- 2272-2279
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2003490678
- Cited by
- 689
- References
- 14
- Citations by year
- 2026: 4 · 2025: 12 · 2024: 14 · 2023: 17 · 2022: 20 · 2021: 28 · 2020: 23 · 2019: 29 · 2018: 29 · 2017: 24 · 2016: 34 · 2015: 36 · 2014: 37 · 2013: 51 · 2012: 52
- FWCI
- 13.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Parathyroid Disorders and Treatments
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Health Sciences › Medicine › Nephrology › Renal function and acid-base balance
- Keywords
- fibroblast growth factor 23, chronic kidney disease, hyperphosphatemia, phosphate homeostasis, renal function decline, phosphate intake, phosphate binders, parathyroid hormone, 1,25-dihydroxyvitamin D, end-stage renal disease, dialysis, kidney transplantation, secondary hyperparathyroidism
- MeSH terms
- Fibroblast Growth Factor-23, Adult, Creatinine, Diet, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Fibroblast Growth Factors, Gels, Humans, Kidney, Kidney Failure, Chronic, Male, Osmolar Concentration, Phosphates, Polyamines, Case-Control Studies, Kidney Transplantation, Renal Insufficiency
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