Fibroblast growth factor 23

Hormone · Phosphatonin alpha-Klotho needed

The principal phosphatonin. Using alpha-Klotho as an obligatory co-receptor for FGFR1 in the proximal tubule, FGF23 lowers serum phosphate by internalising the sodium-phosphate cotransporters, and lowers calcitriol by suppressing CYP27B1 while inducing CYP24A1.

Traced from the start

  1. Phosphate load and hyperphosphataemia
  2. Osteocyte phosphate sensing
  3. Fibroblast growth factor 23

Detail

Co-receptor
Alpha-Klotho is required for high-affinity binding to FGFR1; its expression is largely confined to kidney, parathyroid and choroid plexus, which is what gives FGF23 its tissue selectivity
Phosphate
Internalises and degrades NaPi-IIa (SLC34A1) and NaPi-IIc in the proximal tubule, producing phosphaturia
Vitamin D
Suppresses CYP27B1 (1-alpha-hydroxylase) and induces CYP24A1 (24-hydroxylase), so calcitriol falls
Parathyroid
Directly suppresses PTH secretion in health; in chronic kidney disease the gland loses Klotho and becomes FGF23-resistant, so PTH rises anyway

When it goes wrong

Chronic kidney disease

FGF23 rises earliest of all the mineral markers, before phosphate or PTH move; the calcitriol suppression it causes helps drive secondary hyperparathyroidism, and a high FGF23 tracks left ventricular hypertrophy and mortality

Burosumab, an anti-FGF23 antibody, in X-linked hypophosphataemia

Phosphate reabsorption and calcitriol production are restored and the rickets heals

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