Potassium citrate

Citrate and citric acid solutions are systematic and urinary alkalinizers thereby providing symptomatic relief of dysuria.

When potassium citrate is given orally, the metabolism of absorbed citrate produces an alkaline load. The induced alkaline load in turn increases urinary pH and raises urinary citrate by augmenting citrate clearance without measurably altering ultrafilterable serum citrate. Thus, potassium citrate therapy appears to increase urinary citrate principally by modifying the renal handling of citrate, rather than by increasing the filtered load of citrate. The increased filtered load of citrate may play some role, however, as in small comparisons of oral citrate and oral bicarbonate, citrate had a greater effect on urinary citrate.

In addition to raising urinary pH and citrate, potassium citrate increases urinary potassium by approximately the amount contained in the medication. In some patients, potassium citrate causes a transient reduction in urinary calcium.

The changes induced by potassium citrate produce urine that is less conducive to the crystallization of stone-forming salts (calcium oxalate, calcium phosphate and uric acid). Increased citrate in the urine, by complexing with calcium, decreases calcium ion activity and thus the saturation of calcium oxalate. Citrate also inhibits the spontaneous nucleation of calcium oxalate and calcium phosphate (brushite).

The increase in urinary pH also decreases calcium ion activity by increasing calcium complexation to dissociated anions. The rise in urinary pH also increases the ionization of uric acid to the more soluble urate ion.

Potassium citrate therapy does not alter the urinary saturation of calcium phosphate, since the effect of increased citrate complexation of calcium is opposed by the rise in pH-dependent dissociation of phosphate. Calcium phosphate stones are more stable in alkaline urine.

In the setting of normal renal function, the rise in urinary citrate following a single dose begins by the first hour and lasts for 12 hours. With multiple doses the rise in citrate excretion reaches its peak by the third day and averts the normally wide circadian fluctuation in urinary citrate, thus maintaining urinary citrate at a higher, more constant level throughout the day. When the treatment is withdrawn, urinary citrate begins to decline toward the pre-treatment level on the first day.

The rise in citrate excretion is directly dependent on the potassium citrate dosage. Following long-term treatment, potassium citrate at a dosage of 60 mEq/day raises urinary citrate by approximately 400 mg/day and increases urinary pH by approximately 0.7 units.

In patients with severe renal tubular acidosis or chronic diarrheal syndrome where urinary citrate may be very low (<100 mg/day), potassium citrate may be relatively ineffective in raising urinary citrate. A higher dose of potassium citrate may therefore be required to produce a satisfactory citraturic response. In patients with renal tubular acidosis in whom urinary pH may be high, potassium citrate produces a relatively small rise in urinary pH.

Potassium citrate is absorbed and the citrate is metabolised to bicarbonate. Citric acid is metabolised to carbon dioxide and water. Oxidation is virtually complete with less than 5% of citrate being excreted unchanged in the urine.

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