Calcium oxalate crystallization in undiluted postprandial urine of healthy male volunteers as influenced by citrate.
The crystallization of calcium oxalate (CaOx) in undiluted urine of healthy male volunteers, collected 3 h after intake of a test meal, was evaluated. In two experiments in vitro either the urinary total citrate concentration was increased (urine A) or the urinary pH was elevated (urine B). In one clinical trial the bioequivalence of orally taken potassium citrate (PC) or potassium-sodium citrate (PSC) (n = 9) was studied, in two other trials the dose-response effects of oral PC (n = 8) and oral calcium-sodium citrate (CSC; n = 8). Elevation of urinary citrate (urine A) decreased CaOx crystallization (nucleation, growth, agglomeration time), the crystal content of calcium and oxalate was low and the one of citrate was high. Elevation of urinary pH (urine B) also inhibited CaOx crystallization, the calculated molar ratio free (ionised) citrate/free (ionised) calcium at pH 7.0 was about twice the value observed at pH 5.5, and the ratio complexed citrate/complexed calcium was low. PC and PSC, leading to high urinary citrate and pH, inhibited CaOx crystallization, the former at the stages nucleation, growth and agglomeration, the latter largely beyond nucleation. CSC increased calciuria and crystal growth, but left crystal agglomeration time unchanged. The urinary molar ratio total calcium/total citrate appeared to indicate the state of crystallization, as influenced by alkali containing citrate. It was concluded that 1) application of a technically simple test allows to study CaOx crystallization in undiluted urine; 2) changes in urinary pH and citrate manifest as altered CaOx crystallization, presumably inhibiting this process, the stage of nucleation included, via the action of free citrate and the formation of a calcium citrate complex (stoichiometry < 3:2); 3) oral intake of PC, PSC or CSC modulate differently CaOx crystallization. The significance of these findings, especially with CSC, for renal stone risk is uncertain, but awaits clarification by long-term studies using the described techniques and the calcium/citrate ratio in postprandial urine.
Fan
J
J
Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen, Erlangen, Germany.
Schwille
P O
PO
Schmiedl
A
A
Fink
E
E
Manoharan
M
M
D000328:Adult; D002129:Calcium Oxalate / Q000652:urine*; D002951:Citrates / Q000493:pharmacokinetics / Q000494:pharmacology*; D003460:Crystallization; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D019518:Postprandial Period / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D013810:Therapeutic Equivalency
D002951:Citrates; D002129:Calcium Oxalate; D012964:Sodium; D011188:Potassium