When you eat little salt, your kidneys rely more on a specific channel (ENaC) to hold onto sodium — so blocking it with amiloride makes you pee out a lot more salt. When you eat a lot of salt, that channel isn’t as important, and another part of the kidney (DCT) handles most of the sodium.

When healthy young men eat very little salt, their kidneys rely more on a specific sodium pump (ENaC) in the final part of the kidney to hold onto sodium — and blocking that pump removes as much sodium as blocking the earlier pump.

When healthy young men eat a lot of salt, their kidneys use the part of the tubule that thiazide drugs target to reabsorb more sodium — so when you give them a thiazide, it works way better at making them pee out salt.

When people eat a lot of salt, their kidneys use a specific part (the DCT) to reabsorb more sodium — so when you give them a diuretic like hydrochlorothiazide, it works way better at making them pee out salt.

When healthy young men eat very little salt, their kidneys rely more on a specific sodium pump (ENaC) in the last part of the kidney to hold onto sodium — but when they eat a lot of salt, that pump becomes less important.