Activation of the calcium receptor by a calcimimetic compound halts the progression of secondary hyperparathyroidism in uremic rats

The secondary hyperparathyroidism that develops in rats with chronic renal insufficiency (CRI) can be totally prevented by activation of the parathyro id Ca2+ receptor with a calcimimetic compound, when treatment is initiated before parathyroid cell hyperplasia and increased circulating parathyroid h ormone levels develop. In clinical practice, however, secondary hyperparath yroidism is usually manifest by the time CRI is diagnosed. This study exami ned the effects of daily oral gavage or continuous subcutaneous infusion fo r 8 wk of the calcimimetic NPS R-568 on the progression of established mild or moderate-to-severe secondary hyperparathyroidism in rats with CRI induc ed by 5/6 nephrectomy. Both oral and infused NPS R-568 completely prevented further hyperplasia but did not reduce total parathyroid cell number below that present at the initiation of treatment. This prevention of cellular p roliferation occurred despite increases in plasma phosphate and decreases i n Ca2+ and 1,25-dihydroxyvitamin D levels, and supports the view that the C a2+ receptor is the dominant regulator of parathyroid cell hyperplasia in a ddition to parathyroid hormone secretion. The clinical implications of thes e findings suggest that controlling Ca2+ receptor activity with calcimimeti c compounds could be sufficient to manage secondary hyperparathyroidism in CRI.