Phosphate and FGF-23 !
- Regulation
- For completeness
Phosphate builds bone and stores energy. Bone cells make FGF-23, a hormone that tells the kidney to throw out extra phosphate.
Updated 2026-11-01
Also called: Phosphatonin, Klotho, NaPi-IIa
See it in 3D: Kidneys · Parathyroid glands · Femur
What it is
Phosphate is needed for bone mineral, ATP, nucleic acids and membranes; about 85% of the body's phosphate is in bone. Its blood level is set mainly by the kidney, which reabsorbs most filtered phosphate in the proximal tubule. Two hormones make the kidney excrete phosphate: PTH and FGF-23, a hormone made by osteocytes. FGF-23 also lowers calcitriol, closing a loop between bone, kidney and gut. It rises early in chronic kidney disease.
How it works, step by step
- Dietary phosphate is absorbed in the small intestine, partly through NaPi-IIb, which calcitriol upregulates.
- The kidney filters phosphate and the proximal tubule reabsorbs about 80–90% through NaPi-IIa and NaPi-IIc.
- A rise in phosphate load (and in calcitriol) stimulates osteocytes to secrete FGF-23.
- FGF-23 binds FGFR1–Klotho in the tubule: NaPi transporters are removed from the brush border and phosphate is lost in urine.
- It also suppresses renal calcitriol synthesis, which reduces gut phosphate absorption.
- In CKD fewer nephrons must excrete the load, so FGF-23 climbs; low calcitriol and phosphate retention then drive PTH up.
Hormone axes and feedback
Calcium regulation (PTH, calcitriol, calcitonin)Lesion None (normal)
Tap a box to see the hormone, or choose a lesion to see the lab pattern.
- Stimulates (+)
- Inhibits / negative feedback (−)
- Level ↑
- Level ↓
Reference values
| Parameter | Value | Note |
|---|---|---|
| Serum phosphate, adult | ≈ 2.5–4.5 mg/dL | ≈ 0.81–1.45 mmol/L |
| Serum phosphate, children | higher than adults | supports bone growth |
| Filtered phosphate reabsorbed | ≈ 80–90% | proximal tubule |
| Phosphate stored in bone | ≈ 85% | as hydroxyapatite |
Approximate values for a healthy adult at rest; each laboratory sets its own ranges.
Hormones that set phosphate
| Hormone | Kidney phosphate | Calcitriol | Serum phosphate |
|---|---|---|---|
| PTH | Excretion ↑ | ↑ | ↓ |
| FGF-23 | Excretion ↑ | ↓ | ↓ |
| Calcitriol | Small reabsorption ↑ | — | ↑ (gut absorption) |
Clinical notes
- CKD–mineral and bone disorder: hyperphosphatemia, low calcitriol, high PTH and FGF-23, renal osteodystrophy and vascular calcification.
- Hyperphosphatemia binds calcium, lowering ionized calcium (tetany risk) and depositing calcium phosphate in tissues.
- Severe hypophosphatemia lowers ATP and 2,3-BPG: muscle weakness, respiratory failure, hemolysis and rhabdomyolysis.
- X-linked hypophosphatemia (PHEX mutation) is the most common inherited rickets; calcitriol is low despite low phosphate.
Test yourself
Think of the answer, then tap the question to see it.
In X-linked hypophosphatemia, phosphate is low but calcitriol is not high. Why is that inappropriate, and what causes it?
Low phosphate normally stimulates 1α-hydroxylase. Excess FGF-23 suppresses that enzyme and activates 24-hydroxylase, so calcitriol stays low or normal.
Why does FGF-23 rise before serum phosphate in early chronic kidney disease?
With fewer nephrons, each must excrete more phosphate. Osteocytes raise FGF-23, which increases excretion per nephron and keeps serum phosphate normal for a while.
Why can refeeding a starved patient cause dangerous hypophosphatemia?
Carbohydrate raises insulin, which drives phosphate into cells for glycolysis and ATP synthesis, while total body phosphate is already depleted.
How do PTH and FGF-23 differ in their effect on vitamin D?
Both cause phosphaturia, but PTH stimulates 1α-hydroxylase (more calcitriol) and FGF-23 suppresses it (less calcitriol).
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- Calcium regulation: PTH, vitamin D and calcitonin
- Bone remodeling
- Renal handling of calcium, phosphate and magnesium
- Physiology of acute and chronic kidney failure
- Prolonged fasting and starvation
Related conditions
In Biochemistry
Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.
Sources: 6.7 Calcium Homeostasis: Interactions of the Skeletal System and Other Organ Systems (OpenStax (Rice University), 2022); Phosphate in Blood: MedlinePlus Medical Test (MedlinePlus, US National Library of Medicine, 2025); Chronic Kidney Disease (StatPearls (NCBI Bookshelf), 2024); Rickets: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 80). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).
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Representative model, for educational purposes only.