Theoretical modeling of the urinary supersaturation of calcium salts in healthy individuals and kidney stone patients: Precursors, speciation and therapeutic protocols for decreasing its value

摘要

Background: Supersaturation (SS) of urinary salts has been extensively invoked for assessing the risk of renal stone formation, but precursors have often been ignored. Our objectives were to establish by computer modeling, which urinary components are essential for calculating reliable SS values, to investigate whether unique equilibrium processes occur in the urine of stone formers (SF) which might account for their higher SS levels relative to healthy controls (N), to determine the relative efficacies of three different, widely-used protocols for lowering urinary SS of calcium salts and to examine the influence of precursors. Methods: Urinary data from published studies were consolidated into three N-SF cohort pairs and were selected for modeling using the speciation program JESS. SS values of calcium oxalate monohydrate (COM) and its precursors calcium oxalate di- and tri-hydrate (COD, COT), as well as those of hydroxyapatite (HAP) and its precursors octacalcium phosphate (OCP) and brushite (Bru) were calculated. A pragmatic approach for the statistical analysis of the modeling outputs was developed and applied. Results: Thirteen urinary parameters were identified as being crucial for the accurate calculation of SS of calcium oxalate (CaOx) and calcium phosphate (CaP) salts. Chloride, sulfate and ammonium, or combinations thereof, have frequently been omitted from SS calculations, thereby giving erroneously high values for these parameters. Subtle differences occur in the urinary equilibrium processes of SF and N. SS (OCP) and SS (HAP) are more sensitive to dilution effects than the other urinary salts. Decreasing urinary Ca and decreasing Ox are equally efficacious in reducing SS of CaOx salts, and are marginally superior to increasing urinary volume. Decreasing urinary calcium and increasing urinary volume are equally efficacious in reducing SS of CaP salts. SS of precursors follow the Ostwald Lussac empirical rule and undergo the same changing trends in different urinary scenarios. Conclusions: Researchers are advised to include all of the 13 identified urinary parameters in their calculations of SS of Ca salts, in order to attain better accuracy. Differences in achieving speciation equilibria in N and SF contribute towards higher values of SS in SF, but in a minor way only. Increasing urinary volume is confirmed as the most realistically efficacious strategy for decreasing SS of urinary calcium salts. SS of HAP should be assigned equal importance to that of Bru in considering the stone-forming potential of urine. Precursors of CaOx and CaP salts should be taken into account when investigating stone forming mechanisms.