PTHrP increases phosphate handling in the kidney by which mechanism?

• A. Decreases phosphate excretion
• B. Increases phosphate excretion
• C. No effect on phosphate
• D. Increases phosphate reabsorption

Answer: (B)

PTHrP acts like PTH in the kidney, promoting phosphaturia by reducing how much phosphate the proximal tubule reabsorbs. In the proximal tubule, most phosphate reabsorption is carried out by sodium-phosphate cotransporters such as NaPi-IIa on the apical membrane. When PTHrP binds to its receptor on these cells, it triggers signaling that downregulates the activity and expression of NaPi-IIa (and to some extent NaPi-IIc). With fewer transporters available, less phosphate is reabsorbed from the filtrate, so more phosphate is excreted in the urine.

That’s why increased phosphate excretion is the mechanism here. If phosphate reabsorption were increased, or if there were no effect, excretion wouldn’t rise. The phosphaturic effect mirrors the classic action of PTH on the kidney, and explains why PTHrP can cause phosphaturia in conditions where it is elevated.