the colas, the associated low intake of calcium-rich beverages, or the phosphorus itself.

Except as noted in very young infants, none of these adjustments in calcium-regulating hormones is clearly adverse in its own right, particularly if calcium intake is adequate. Hence these effects do not provide a useful basis for estimating the Tolerable Upper Intake Level (UL).

Metastatic Calcification

The most serious, clearly harmful effect of hyperphosphatemia is calcification of nonskeletal tissues. This occurs when the calcium and phosphorus concentrations of ECF exceed the limits of solubility for secondary calcium phosphate (CaHPO4). This critical concentration is strongly dependent on amounts of other ions in the ECF, especially HCO3 citrate, H+, and K+, and so cannot be unambiguously defined. However, tissue calcification virtually never occurs at ECF calcium × phosphorus ion products less than ~4 (mmol/liter)2 [~1 (mg/dl)2]. Although ECF in adults is normally less than half-saturated with respect to CaHPO4, elevation of plasma Pi, if extreme, can bring the ECF to the point of saturation. Although both calcium and phosphate are involved in such ectopic mineralization, ECF calcium levels are tightly regulated and are usually affected little by even large variations in calcium intake. By contrast, the sensitivity of ECF Pi to joint effects of diet and renal clearance means that an elevation in ECF Pi will usually be the cause of supersaturation. When calcification involves the kidney, renal function can deteriorate rapidly, renal phosphorus clearance drops, and ECF Pi rises yet further, leading to a rapid downhill spiral.

Under saturated conditions, susceptible tissue matrices will begin to accumulate CaHPO4 crystals, particularly if local pH rises above 7.4. Saturation of ECF with respect to calcium and phosphorus almost never occurs in individuals with normal renal function, mainly because urine phosphate excretion rises in direct proportion to dietary intake. As Figure 5-1 shows, the upper limit of the normal adult range for serum Pi typically occurs at absorbed intakes above 2.2 g (71 mmol)/day. At 62.5 percent absorption, that means ingested intakes above 3.4 g (110 mmol)/day. The 1994 CSFII data indicate that the reported intake at the ninety-fifth percentile was 2.5 g (81.7 mmol)/day in boys aged 14 through 18 years (see Appendix D). Hyperphosphatemia from dietary causes becomes a problem mainly in patients with end-stage renal disease or in such conditions as vitamin D intoxication. When functioning kidney tissue mass is reduced to less than ~20 percent of normal, the GFR becomes too low to clear typical absorbed loads of dietary phospho-

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