Urinary citrate and renal stone disease: the preventive role of alkali citrate treatment.

Hypocitraturia or low urinary citrate excretion is a common feature in patients with nephrolithiasis, particularly in those with calcium stone disease. Citrate is a weak acid that is synthesized inside Krebs' cycle. It can also enter the body through dietary intake. Differences in intestinal handling, serum concentration as well as filtered load of citrate were not found between kidney stone formers and normal subjects. On the contrary, several metabolic abnormalities, such as metabolic acidosis, hypokalemia and starving, seem to influence the renal handling of citrate by inducing a decrease in the urinary citrate excretion. Hypocitraturia is defined as urinary citrate excretion lower than 320 mg/day. Literature data show a large prevalence of hypocitraturia in patients with nephrolithiasis, ranging from 8% up to 68.3%. The protective role of citrate is linked to several mechanisms; in fact citrate reduces urinary supersaturation of calcium salts by forming soluble complexes with calcium ions and by inhibiting crystal growth and aggregation. Furthermore, citrate increases the activity of some macromolecules in the urine (eg. Tamm-Horsfall protein) that inhibit calcium oxalate aggregation. Citrate seems able to reduce the expression of urinary osteopontin. A role of citrate in pathogenesis of metabolic bone diseases has been recently suggested and citrate measurement in urine has been proposed as a predictor of both bone mass loss and fracture risk. Idiopathic calcium stone disease, with or without hypocitraturia, can be treated with alkaline citrate, as well as other forms of nephrolithiasis and different pathological conditions. The therapy with potassium citrate, or magnesium potassium citrate, is commonly prescribed in clinical practice in order to increase urinary citrate and to reduce stone formation rates. Our data as well as those of the literature confirm that alkali citrate induces both an increase of protective urinay analytes (eg. citrate, potassium and pH) and a decrease of calcium oxalate supersaturation. Moreover, alkali treatment reduces the rate of stone recurrence and increases the clearance rates and dissolution of stone fragments. Last but not the least, an increasing number of papers pointed out the protective role of alkali citrate in preserving bone mass in stone formers as well as in healthy subjects with bone loss. Nevertheless, the evaluation of urinary citrate in patients with kidney stones and the treatment of these patients with alkali salts namely with potassium citrate are still scarce.