Calcium Oxalate Crystallization in Undiluted Urine of Healthy Males: in Vitro and in Vivo Effects of Various Citrate Compounds

We evaluated the crystallization of calcium oxalate (CaOx) in undiluted urine, collected 3 hours after intake of a test meal by healthy males. In two experiments in vitro, either the total citrate concentration was increased (urine A) or the pH was elevated (urine B). In addition, in three clinical trials, the bioequivalence of orally taken potassium citrate (PC) and potassium-sodium citrate (PSC) (n = 9), and the dose-response effects of oral PC (n = 8) and oral calciumsodium citrate (CSC; n = 8) were studied. Elevation of urinary citrate (urine A) decreased CaOx crystallization (nucleation, growth, agglomeration time), and increased the calcium and citrate content of the crystallized mass; elevation of urinary pH (urine B) also suppressed CaOx crystallization, the calculated molar ratio ionized citrate/ionized calcium at pH 7 was about twice the value observed at pH 5.5, and the ratio complexed citrate/complexed calcium was low. PC and PSC inhibited CaOx crystallization to a similar extent. CSC increased crystal growth but left agglomeration time unchanged. The urinary molar ratio (total calcium/total citrate) appeared to be directly related to the CaOx crystal growth rate. We concluded that: (1) changes in urine pH, citrate, and calcium are reflected by CaOx crystallization; (2) free citrate and a calcium citrate complex (stoichiometry ≤ 1:1) inhibit CaOx crystallization; (3) in individuals taking PC, PSC or CSC, the renal stone risk may be characterized using the presented CaOx crystallization test and the urinary calcium/citrate ratio.