Treatment of primary hypercalciuria: Potassium citrate
Citrate supplementation, as alkaline potassium salt, was formerly introduced in the treatment of distal renal tubular acido- sis and subsequently extended to idiopathic hypocitraturic calcium nephrolithiasis. Regardless of the accompanying cation (sodium, potassium, magnesium) citrate salts exhibit direct effects on calcium excretion, acting by two distinct mechanisms: first, citrate anion is a strong ligand of calcium, and this will result in a decrease in free ionised calcium concentration; second, alkalinisation is expected to reduce bone resorption, thereby decreasing total calcium excretion. The principal effect of citrate on calcium excretion is due to its ability to bind calcium, so that the calcium-citrate soluble complex accounts for by about 10 to 40% of total urinary calcium (Figure 1). Therefore, an increase in urinary citrate will result in a decrease in the fraction of free-ionised calcium, which is the species thermodynamically important for the saturation of calcium forming salts.
The effect of potassium citrate upon the skeleton is shared by other alkaline salts, such as potassium bicarbonate. In fact, in postmenopausal women, the oral administration of potassium bicarbonate, at a dose sufficient to neutralise endogenous acid, improved calcium balance, by reducing calcium excretion, through a reduction of bone resorption and an increase in the rate of bone formation. In a prospective short-term study, alkaline mineral water induced a significant reduction in the biochemical markers of bone resorption. There also are recent reports of a specific effect of potassium intake on calcium excretion, because it has been found that potassium deficiency increases, whereas potassium supplementation as either citrate or bicarbonate or chloride salts, decreases calcium excretion. Potassium citrate, given to healthy menopausal women decreased net acid excretion and concurrently decreased markers of bone resorption (Figure 2). Percent variations of urine citrate were inversely related to those of de- oxypyridinolines and hydroxyproline, whereas calcium excretion exhibited only minor decreases .
Figure 1 – Dependence offree ionised calcium on citrate in urine specimens at two different total calcium concentrations.
Figure 2 – Effetcs of a three-month course of potassium citrate on bone metabolism and calcium excretion in post-menopausal women. Treated women (panel A) are compared to untreated ones (panel B) (**p<0.001 vs baseline; **p<0.01 vs baseline).