Correspondence

Age, Renal Tubular Phosphate Reabsorption, and Serum Phosphate Levels in Adults

N Engl J Med 2008; 359:864-866August 21, 2008

Article

To the Editor:

A relation between age and serum phosphate levels in adults has been recognized since 1969.1 We used data from the Gubbio Population Study to analyze serum phosphate levels and renal phosphate handling in relation to age in 2107 men and 2560 women (age range, 18 to 97 years).2 Information concerning medical history and diet was collected by questionnaire. Overnight urine samples were obtained for analysis of albuminuria and markers of protein and salt intake. Early-morning samples of blood and urine were collected under fasting conditions to examine renal tubular function. Renal tubular phosphate handling was assessed as the ratio of the maximum rate of tubular phosphate reabsorption to the glomerular filtration rate (TmP:GFR).3 Laboratory analyses were performed with the use of an autoanalyzer, with an intraassay error of less than 5% for serum variables and of less than 10% for urinary variables.

Among men, serum phosphate levels declined with age almost linearly (Figure 1Figure 1Serum Phosphate and Maximum Tubular Phosphate Reabsorption in Adults, According to Age., top graph). Serum phosphate levels in women under the age of 45 years overlapped with those in men and then increased between the ages of 45 and 54 years before progressively declining from 55 years. The age-associated decline in serum phosphate levels was not associated with hypocalcemia and hypocalciuria, nor with indexes of protein and salt intake (not shown). The increase in serum phosphate levels in women between the ages of 45 and 54 years was probably not related to age itself, but rather to menstrual status, since serum phosphate levels were higher in 97 menopausal women under 50 years of age (mean age, 44.8 years) than in 67 menstruating women 50 years of age or older (mean age, 51.6 years) (3.61 mg per deciliter [1.17 mmol per liter] and 3.45 mg per deciliter [1.11 mmol per liter], respectively; P=0.04). In both sexes, the decrease in the TmP:GFR ratio with age was similar to that in serum phosphate levels (Figure 1, bottom graph).

Thus, in adults, serum phosphate levels decline with age, except for a transient increase during the perimenopausal period in women.4 The age-associated decline in serum phosphate levels reflects changes in tubular phosphate reabsorption, which, in turn, might be explained by age-dependent changes in tubular phosphate handling or in its hormonal modulators (e.g., parathyroid hormone, phosphatonins, and growth hormone). The lack of association between the decrease in serum phosphate levels with hypocalcemia or hypocalciuria does not support a role for hyperparathyroidism caused by vitamin D deficiency. A possible mechanism might be the age-dependent decrease in growth-factor secretion and related stimulation of phosphate reabsorption.5 The practical implication is that phosphate-depleting disorders might induce hypophosphatemia more readily in older persons because the tubular capacity for phosphate reabsorption and the level of serum phosphate before the development of such disorders are already diminished. For parallel reasons, disorders causing increases in serum phosphate levels should more readily induce hyperphosphatemia in younger persons.

Massimo Cirillo, M.D.
Second University of Naples, 80131 Naples, Italy
massimo.cirillo@unina2.it

Carolina Ciacci, M.D.
Federico II University, 80131 Naples, Italy

Natale G. De Santo, M.D.
Second University of Naples, 80131 Naples, Italy

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