Variability of the calcium ion activity with pH in stone-forming and non-stone-forming urine

In recurrent renal stone-formers (N = 20) and matched healthy adults (N = 20), the actual activity of ionized calcium (alpha Ca2+) and pH were determined in whole urine with an ion-selective electrode. No significant difference was found for the actual median activity of ionized calcium, however the actual median pH was significantly higher in stone-formers compared to healthy adults (pH = 5.57 vs. pH = 5.24; p < 0.005). The relationship between Ca2+ activity and pH was studied in each collected urine by titration with HCl/NaOH. In all urines the Ca2+ activity decreased with increasing pH in a typical bifasic manner. All curves showed a characteristic "breaking point" at a similar median pH in the stone-formers and in the healthy adults (pH = 6.81 vs. pH = 6.77) (NS). However the slope of the curves in the stone-formers and healthy adults changed from a median value of delta lg alpha Ca2+/delta pH of -0.139 and -0.173 (NS) respectively, to a highly significant difference of -1.326 and -1.053 (p < 0.0001) between the groups, indicating increased binding/precipitation of Ca2+ in stone-formers than in healthy adults supporting the theory of the lack of inhibitors in stone-formers. The strong relationship between the activity of ionized calcium and pH, combined with a higher actual pH and a higher decrease of ionized calcium with pH in stone-formers than in healthy adults, indicates hydrogen ion as a major factor in stone-formation. The close relationship between Ca2+ activity and pH indicates the need for simultaneous measurements of the pH in order to interpret data for the Ca2+ activity. In order to preserve a low urinary pH, where Ca2+ is predominantly in a free ionic state, our results suggest that treatment with acidifying salts could be a logical choice in order to prevent stone-formation.