FGF23 (fibroblast growth factor 23) is produced by osteocytes in response to hyperphosphataemia and elevated vitamin D. The primary renal action of FGF23 (acting via FGFR1-Klotho receptor complex) is:

• A Increases NaPi-IIa transporter expression in proximal tubule, retaining phosphate
• B Decreases NaPi-IIa and NaPi-IIc phosphate cotransporter expression, increasing renal phosphate excretion; also suppresses CYP27B1 (1-alpha-hydroxylase) reducing calcitriol synthesis ✓
• C Activates PTH secretion from parathyroid glands to indirectly increase phosphate excretion
• D Increases TRPV5/6 calcium channels in distal tubule to retain calcium with phosphate

Explanation

FGF23 is the primary phosphatonin hormone. Acting on proximal tubular cells through the FGFR1c/Klotho co-receptor complex, FGF23 triggers internalisation and degradation of NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3) sodium-phosphate cotransporters, dramatically increasing urinary phosphate excretion (phosphaturia). Simultaneously, FGF23 suppresses CYP27B1 (1-alpha-hydroxylase) expression and upregulates CYP24A1 (24-hydroxylase), reducing active vitamin D (1,25-OH2D3) synthesis. This prevents vitamin D-mediated intestinal phosphate absorption. The combined effect keeps serum phosphate from rising excessively. In CKD, elevated FGF23 precedes clinical hyperphosphataemia and is associated with cardiovascular mortality. FGF23 does not activate PTH or affect calcium channels in the distal tubule.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.