Potassium Citrate

When potassium citrate is taken by mouth, the body breaks down the absorbed citrate and this produces an alkaline load. That alkaline load raises the pH of the urine, and it also raises urinary citrate, mainly by increasing how fast the kidneys clear citrate. The level of citrate in the blood that can be filtered does not change in any measurable way. So potassium citrate seems to raise urinary citrate mostly by changing how the kidneys handle it, not by putting more citrate through the filter. A larger amount of filtered citrate may still play a part, though. In a few small comparisons, oral citrate raised urinary citrate more than oral bicarbonate did.

Besides raising urinary pH and citrate, potassium citrate increases urinary potassium by roughly the amount of potassium in the medicine. In some patients it causes a short-lived drop in urinary calcium.

These changes make the urine less likely to let stone-forming salts crystallise. Those salts are calcium oxalate, calcium phosphate and uric acid. Citrate in the urine binds to calcium, which lowers the amount of free calcium ion and so reduces how saturated the urine is with calcium oxalate. Citrate also stops calcium oxalate and calcium phosphate (brushite) from forming crystals on their own.

A higher urinary pH also lowers free calcium ion, because more calcium binds to the anions that have dissociated. The same rise in pH turns more uric acid into urate ion, which is more soluble.

Potassium citrate does not change how saturated the urine is with calcium phosphate. The extra citrate binding calcium is cancelled out by the way higher pH causes phosphate to dissociate. Calcium phosphate stones are more stable in alkaline urine.

With normal kidney function, the rise in urinary citrate after a single dose starts within the first hour and lasts for 12 hours. With repeated doses, citrate excretion reaches its highest level by the third day. It also evens out the usual large swings in urinary citrate across the day, so the level stays higher and steadier. When treatment is stopped, urinary citrate starts falling back towards its level before treatment on the first day.

The rise in citrate excretion depends directly on the dose. After long-term use, a dose of 60 mEq a day raises urinary citrate by about 400 mg a day and raises urinary pH by about 0.7 units.

In patients with severe renal tubular acidosis or chronic diarrhoeal syndrome, urinary citrate can be very low (below 100 mg a day). Potassium citrate may then do little to raise it, so a higher dose may be needed to get a satisfactory citrate response. In patients with renal tubular acidosis whose urinary pH is already high, potassium citrate raises the pH only slightly.