Kinetics of 1,25-dihydroxyvitamin D metabolism in the aging rat

To determine whether postmaturational aging influences the kinetics of 1,25-dihydroxyvitamin D [1,25(OH)2D] metabolism in the rat, we measured the metabolic clearance (MCR) and production (PR) rates of 1,25(OH)2D in 6-, 12-, 18-, and 24-mo-old Fischer 344 rats using the constant infusion method. Plasma calcium, phosphorus, and parathyroid hormone (PTH), urinary calcium and phosphorus, and glomerular filtration rate (GFR) were also measured. MCR and PR increased 57 and 91%, respectively (when expressed per rat), and 32 and 39%, respectively (when expressed per kg body wt), between 6 and 24 mo of age, with the greatest increase occurring between 18 and 24 mo. The plasma concentration of 1,25(OH)2D remained unchanged. Plasma PTH, when compared with 6-mo-old animals, was significantly elevated at 18 mo (147%) and even higher at 24 mo (240%). GFR (51Cr-labeled EDTA clearance) remained unchanged through 18 mo but tended to be reduced at 24 mo. Plasma phosphorus tended to decrease with age, whereas plasma calcium, urinary calcium, and urinary phosphorus did not differ among the age groups. These data indicate that both clearance and production of 1,25(OH)2D increase with postmaturational aging in the rat. They also suggest that the early age-related rise in plasma PTH is neither a consequence of low plasma calcium nor of renal insufficiency.