Effects of different doses of alkaline citrate on urine composition and crystallization of calcium oxalate

Abstract

Prophylactic treatment with alkaline citrate in patients with recurrent calcium oxalate (CaOx) stone disease results in reduced CaOx supersaturation and increased urinary citrate. The effects of a single evening dose were compared with those of two and three daily doses in six recurrent CaOx stone formers with hypercalciuria, hypocitraturia or raised calcium/citrate quotients. While on a standardized hospital diet the patients were given 7.5 g (28 mmol) of sodium potassium citrate (URALYT-U) in one, two, and three doses. Fractional urine collections during 24 hours were analyzed for pH, composition, and crystallization risk (CR). All dosage regimens had favourable effects on urinary calcium, citrate, calcium/citrate quotients, and CaOx-CR. The most sustained effect was recorded with three divided doses. Single evening doses resulted in the most pronounced effects between 22.00-06.00 h, thereby counteracting the increased risk of CaOx crystallization during that period. In terms of 24h urine composition the best effect was recorded with alkaline citrate administered three times daily, but because of the favourable response by a single evening dose between 22.00-06.00 h the assumption was made that this dosage regimen might be sufficient to reduce the risk of CaOx crystallization and stone formation. However, the validity of such an assumption can only be established by long-term clinical studies.

A new approach to studying inhibitors of calcium oxalate crystal growth

“…di-and tricarbocylic acids and pyrophosphate. Some of these compounds occur naturally in the urine or are already used in the treatment of nephrolithiasis [3,6]. The inhibitors' behaviour regarding the medium was studied without any assumptions about their possible mechanisms of action.…”

Citrate and urease-induced crystallization in synthetic and human urine

“…That citrate causes an increase in urine pH is well known and is used therapeutically to prevent calcium stone formation [2,4]. The main physiological effects of citrate addition are not only an increase in urinary pH but also a decrease in urinary calcium.…”

“…In some individuals urinary colonization by urease-producing microorganisms does not lead to the formation of any concrements whereas in others there is rapid formation of large staghorn stones. Diversity in urinary citrate composition may explain the differing susceptibility of patients to forming infection stones in the presence of UTI with urease-producing microorganisms [10,11,13,14].Calcium oxalate urine crystallization is inhibited by glycosaminoglycans, citrate, magnesium, pyrophosphate, and proteins [2,3,4,6,8,9]. Some reports claim that citrate is one of the most potent inhibitors [2,6,8].…”

Metaphylaxis in Pediatric Urinary Stone Disease

“…The daily dose may include 1-3 mEq/kg, depending on the urine pH and the primary disease, and the dose may be as high as 5-8 mEq/kg for infants with distal RTA [45]. Ideally, three doses a day should be administered, and if only one dose is possible, it should be administered in the evening [46].…”