Renal proximal tubule: phosphate handling

Target organ · NaPi-IIa / NaPi-IIc Phosphaturia

Some 80-90% of filtered phosphate is reclaimed by the sodium-phosphate cotransporters NaPi-IIa and NaPi-IIc on the proximal brush border. PTH and FGF23 both cause these transporters to be internalised and degraded, so both hormones waste phosphate in the urine.

Traced from the start

  1. Fall in ionised calciumRise in ionised calcium
  2. Calcium-sensing receptor on parathyroid chief cells
  3. Phosphate load and hyperphosphataemia
  4. Osteocyte phosphate sensing
  5. Parathyroid hormoneFibroblast growth factor 23
  6. Renal proximal tubule: phosphate handling

Detail

Transporters
Apical, sodium-driven NaPi-IIa (SLC34A1) and NaPi-IIc (SLC34A3)
Inhibited by
PTH and FGF23, which both internalise the transporters; also dopamine and glucocorticoids
Measure
The renal phosphate threshold TmP/GFR separates renal phosphate wasting from redistribution or poor intake
Side effect of PTH here
PTH also inhibits proximal NHE3 and bicarbonate reabsorption, which is why marked PTH excess gives a mild hyperchloraemic metabolic acidosis

When it goes wrong

Primary hyperparathyroidism

Hypophosphataemia with inappropriate phosphaturia alongside the hypercalcaemia; the low phosphate is what separates it from most other causes of hypercalcaemia

Proximal tubular injury in Fanconi syndrome (myeloma, tenofovir, ifosfamide, Wilson disease)

Phosphaturia with glycosuria, aminoaciduria and a proximal renal tubular acidosis, producing hypophosphataemic osteomalacia

Practise this structure

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