DEPENDENCE OF UPPER LIMIT OF METASTABILITY ON SUPERSATURATION IN NEPHROLITHIASIS

Formation of renal stones requires supersaturation (SS) high enough to induce crystallization; such a SS is referred to as the upper limit o f metastability (ULM). The ULM for calcium oxalate (CaOx) or calcium p hosphate can be measured by adding oxalate or calcium to urine, respec tively, and noting the point at which overt crystallization occurs as evidenced by clouding. In principle, the urine should be more prone to form stone crystals as its SS approaches the ULM, and the SS ULM dist ance has been used as an index of stone forming potential. In addition , one would expect the ULM and initial SS to be unrelated, as the star ting urine SS has no apparent link to the amount of calcium or oxalate that urine can dissolve without leading to crystal formation. However , in rats, we have found a surprising correlation between ULM and SS, such that ULM appears to rise with initial SS, for CaOx, and, to a les ser extent, for brushite (Br), a typical calcium phosphate initial pha se. In this study, we measured CaOx and Br ULM, and SS, in urine of 50 patients and 11 normal people. to determine if ULM and SS were correl ated, as in rats, and to explore the relationship between SS and ULM. We found the same dependence of ULM on SS as in rats, for both CaOx an d Br, and found no differences between patients and normal people with respect to this dependency. However, for Br, patients showed a lower ULM than normals, but the same initial SS, meaning that patients were closer to their crystal formation threshold than normals. Treatments f or stones had no apparent effect on the SS-ULM dependency. We conclude that in humans, as in rats, ULM is related to initial SS, and that th is relationship is the same in patients as in normals for CaOx, but sh ifted in a stone forming direction for Br among patients. The ULM-SS i nteraction is unaffected by contemporary conventional stone treatments , and is more marked for CaOx than Br. The mechanisms of the dependenc e are unknown. The smaller difference between ULM and initial SS for B r in patients than normal supports prior evidence suggesting a defect in stone patients that could lead to calcium phosphate crystallization , subsequent nucleation of CaOx, and stone disease.