Proximal tubule: phosphate reabsorption and PTH

Proximal tubule · detail · NaPi-IIa PTH FGF23

About 80-85% of filtered phosphate is reclaimed by apical sodium-phosphate cotransporters in the proximal tubule. PTH and FGF23 retrieve these transporters from the membrane, making the proximal tubule the site of the kidney's phosphate regulation.

Traced from the start

  1. Glomerular filtration barrier
  2. Proximal tubule: phosphate reabsorption and PTH

Detail

Reabsorbs
80-85% of filtered phosphate (transport-maximum limited); also ~65% of filtered Ca2+ passively (paracellular, solvent drag) and ~15-20% of Mg2+
Transporter
Apical NaPi-IIa and NaPi-IIc (Na+-phosphate cotransport)
Hormone
PTH (PTH1R, cAMP/PKA) and FGF23 (FGFR-Klotho) internalise NaPi-IIa causing phosphaturia; PTH also stimulates 1-alpha-hydroxylase here to make calcitriol
Diuretic
None specific; acetazolamide and SGLT2 inhibitors modestly increase phosphate excretion

When it goes wrong

Primary hyperparathyroidism

Hypercalcaemia with hypophosphataemia and raised urinary phosphate; hypercalciuria despite PTH-driven distal calcium reabsorption because the filtered calcium load rises

X-linked hypophosphataemic rickets (PHEX mutation, excess FGF23) or Fanconi syndrome

Renal phosphate wasting with low TmP/GFR, rickets in children, osteomalacia in adults

Falling nephron mass in CKD

Phosphate retention despite rising FGF23 and PTH: secondary hyperparathyroidism and mineral bone disease

Practise this structure

1 question in the bank tagged Parathyroid.