Phosphate Handling by the Kidney

Expansion

• About 80 to 90 per cent of filtered phosphate is reabsorbed in the proximal tubule by sodium-phosphate (NaPi) cotransporters
• Phosphate also acts as the main urinary buffer, forming titratable acid

Phosphaturic hormones, which remove NaPi transporters from the membrane:

• Parathyroid hormone
• FGF23, from osteocytes, which also suppresses calcitriol synthesis

In chronic kidney disease the sequence is important:

1. Falling GFR retains phosphate
2. FGF23 rises first, maintaining phosphate excretion but suppressing calcitriol
3. Reduced calcitriol lowers calcium absorption from the gut
4. Hypocalcaemia and hyperphosphataemia drive secondary hyperparathyroidism
5. The result is renal osteodystrophy and vascular calcification

This explains treatment: phosphate binders, calcitriol analogues and calcimimetics, all aimed at different points in the same chain.