STONE DISEASE

Rapid Communication: Relative effect of urinary calcium and oxalate on saturation of calcium oxalate
Pak CY, Adams-Huet B, Poindexter JR, Pearle MS, Peterson RD, Moe OW
Center for Mineral Metabolism and Clinical Research, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-8571, USA
Kidney Int. 2004; 66: 2032-7

• Background: The study compared the effect of urinary calcium with that of oxalate on urinary saturation [relative saturation ratio (RSR)] of calcium oxalate.
• Methods: A retrospective data analysis was conducted on urinary stone risk analysis from 667 patients with predominantly calcium oxalate stones. Urinary RSR of calcium oxalate was individually calculated using Equil 2. A “theoretical” curve of the relationship between urinary RSR of calcium oxalate and concentration of calcium or oxalate was obtained at two stability constants for calcium oxalate complex, while varying calcium or oxalate and using group mean values for urinary constituents.
• Results: At the stability constant of 7.07 x 10(3), the increase in RSR of calcium oxalate was less marked with calcium than with oxalate. However, at the stability constant of 2.746 x 10(3) from the Equil 2 that is considered the “gold standard,” calcium and oxalate were equally effective in increasing RSR of calcium oxalate. The above theoretical curves (relating RSR with calcium or oxalate) were closely approximated by the actual curves constructed with data from individual urine samples. Urinary saturation of calcium oxalate was equally dependent on urinary concentrations of calcium and oxalate (r = 0.75 unadjusted and 0.57 adjusted for variables, and P < 0.0001 for calcium; r = 0.73 unadjusted and 0.60 adjusted, P < 0.0001 for oxalate).
• Conclusion: Among calcium oxalate stone-formers, urinary calcium is equally effective as urinary oxalate in increasing RSR of calcium oxalate.
  
  
• Editorial Comment
  It has long been held that urinary oxalate is a more important contributor to calcium oxalate stone formation than urinary calcium. This perception stems from work published in 1972 by Nordin, Peacock and Wilkinson (1) in which the relationship of urinary calcium and oxalate concentration on urinary saturation calcium oxalate was determined using the stability proposed by Robertson of 7.07 x 10(3). Their work showed that although urinary saturation of calcium oxalate initially increased with increasing urinary calcium concentration, saturation reached a plateau at moderate calcium concentration; in contrast, saturation of calcium oxalate continued to rise with increasing urinary oxalate concentration, thereby supporting a more pronounced effect of urinary oxalate than calcium on urinary saturation of calcium oxalate. Although Robertson later adjusted his stability constant, in line with a lower stability constant proposed by Finlayson (2), the relationships between urinary calcium and oxalate and urinary saturation of calcium oxalate were never re-assessed.
  Pak and colleagues reexamined the relative contribution of urinary calcium and oxalate on urinary saturation of calcium oxalate using retrospective data from predominantly calcium oxalate stone formers in their stone registry. First, they constructed theoretical curves relating urinary calcium and oxalate concentrations to urinary saturation of calcium oxalate using average values for urinary analyses derived from the population of patients studied and varying the urinary calcium and oxalate concentrations from zero to 2 standard deviations above the mean of the patient-derived values. When the higher original Roberson stability constant was used, urinary saturation reached a plateau at relatively lower concentrations of urinary calcium than urinary oxalate. On the other hand, when the lower Finlayson stability constant was used (as is used in the Equil 2 computer program, considered the gold standard for calculating saturation of stone-forming salts), saturation increased with both urinary calcium and oxalate concentrations, with the 2 curves departing only at high concentrations, at which point the curves reached a plateau at relatively lower calcium than oxalate concentrations. Furthermore, when actual urinary saturations were plotted against urinary calcium and oxalate concentrations for the patients in the database using the 2 stability constants, the “actual” values closely approximated the “theoretical” values derived using the lower Finlayson stability constant. Of significance, the calcium and oxalate curves were nearly superimposable.
  These findings suggest that urinary calcium and oxalate contribute equally to the tendency toward calcium oxalate stone formation. As such, recent studies downplaying the role of dietary calcium in stone formation and advising against calcium restriction for stone prevention should be viewed cautiously. Indeed, urinary calcium, among stone risk factors, has most consistently been shown to be associated with risk of calcium stone formation. Although these findings in no way minimize the contribution of oxalate to calcium oxalate stone formation, both dietary calcium and oxalate should be taken into account when recommending dietary measures for stone prevention and efforts to reduce both levels in the urine may result in reduced stone formation rates.

References
1. Nordin BEC, Peacock M, Wildinson R: Hypercalciuria and calcium stone disease. Clin Endo Metab. 1972; 1: 169-83.
2. Finlayson G, Roth R, BuBois L: Calcium Oxalate Solubility Studies in Urinary Calculi, Madrid, International Symposium on Renal Stone Research, 1972, pp 1-7.

Dr. Margaret S. Pearle
Associate Professor of Urology
University of Texas Southwestern Med Ctr
Dallas, Texas, USA