The role of phosphorus in the of secondary hyperparathyroidism and parathyroid cell proliferation in chronic renal failure

Hyperplasia of the parathyroid glands and high levels of parathyroid hormon e (PTH) are among the most consistent findings in patients with chronic ren al, failure. In early renal failure, alterations in vitamin D metabolism pl ay a key role in the development of secondary hyperparathyroidism. Low leve ls of calcitriol and decreased expression of the vitamin D responsive eleme nt may allow greater synthesis and secretion of PTH, Phosphorus independent of serum calcium and calcitriol increases PTH synthesis and secretion by a post-transcriptional mechanism. Studies in vivo in uremic rats demonstrate d that an increase in dietary phosphorus induces parathyroid gland hyperpla sia, If the rats are then fed a low-phosphorus diet, the levels of serum PT H return to normal; however, the size of the parathyroid glands remains enl arged. No apoptosis was observed in the glands, To further characterize the effects of phosphorus on PTH synthesis and secretion, intact rat parathyro id glands. were metabolically labeled during a 4-hour incubation in methion ine-free medium containing 1.25 mM Ca2+, [S-35]methionine, and either 2.8 m M or 0.2 mM phosphorus. Total PTH secretion, as measured in the medium, was increased more than 6-fold in glands incubated in high-phosphorus medium c ompared with glands incubated in the low-phosphorus medium. Thus, in the pa st 20 years, numerous investigators have provided strong evidence for the a ction of phosphorus on PTH secretion, Unfortunately, the absence of a parat hyroid cell line is slowing the progress in understanding the molecular mec hanism(s) involved in phosphorus regulation of PTH.