One of the points I took away from this talk is that we need to re-evaluate the role of the “calcium-phosphate product” in clinical medicine. Presently, the KDOQI guidelines state that nephrologists should attempt to maintain the Ca x P product below 55 in order to minimize pathologic calcification. I had always been taught that if the Ca x P product exceeds 55, there is a tendency for calcium phosphate to precipitate and deposit within the walls of blood vessels. Is this true?
This 20007 KI review (“The Fallacy of the calcium-phosphorus product“) makes the case that this view is erroneous. The majority of medial calcification seen in CKD/ESRD patients is in the form of hydroxyapatite, which is much more complex than calcium phosphate; the chemical structure is Ca10(PO4)6(OH)2. As the formation of hydroxyapatite involves multiple separate steps, it is very unlikely to occur spontaneously. A more likely scenario is that a local balance between specific calcification inhibitors (e.g., pyrophosphate) and activators (e.g., alkaline phosphatase) maintained at a local level determines whether or not pathologic calcification occurs. Furthermore, experiments in which exogenous calcium and phosphate were added to samples of human plasma demonstrated that calcium-phosphate precipitation did not occur until the Ca x P product exceeded over 200–a number which is never achieved in human patients.
Nonetheless, despite these potential flaws in the physiologic rationale for the Ca x P product, there is abundant epidemiologic evidence showing an association between the Ca x P product and cardiovascular mortality. Perhaps this simply reflects the observation that serum calcium and serum phosphate levels each independently potentially contribute to pathologic calcification. In any case, the prevailing current approach is to control serum phosphate levels with binders to within the normal range as much as possible while tolerating some degree of mild hypocalcemia.