Calcium oxalate (CaOx) and calcium phosphate (CaP) crystals do not pre
cipitate in large amounts in normal urine despite considerable supersa
turation (SS), partly because urine inhibits crystal nucleation, aggre
gation, and growth. In normal rats and rats bred for hypercalciuria (G
HS), we varied SS by varying calcium intake to test the hypothesis tha
t increased SS might deplete inhibitors and reduce inhibition of cryst
al formation. In normal rats when compared to a low calcium diet (0.02
% Ca), a high calcium diet (1.2% Ca) raised the SS of CaOx from 0.8 to
8.2. The high calcium diet also raised the upper limit of metastabili
ty (ULM) of CaOx (the SS at which crystals form in urine) from 11.8 to
36. In GHS rats, diet change altered CaOx SS from 1.5 to 12, and ULM
from 17 to 50 (all differences, P < 0.001). Because ULM rose with SS,
the increased SS had little potential to increase CaOx stone risk. For
CaP, however, SS rose From 0.6 to 2.4 and 1.1 to 8 in normal and GHS
rats (P < 0.001 for both), respectively, whereas ULM for CaP did not i
ncrease significantly (8 vs. 7 and 7 vs. 11: P = NS, both changes). Th
erefore, CaP SS rose close to the ULM, posing a high stone risk. The s
tones formed by these rats are composed of CaP. Increasing CaOx SS by
diet raises ULM for CaOx thereby offsetting the risk of CaOx stones in
rats.