Secondary hyperparathyroidism (secondary HPT), a common disorder in
chronic renal failure (CRF) patients, is characterized by hypersecretion of
parathyroid hormone (PTH), parathyroid
hyperplasia, and decreased expression of the
calcium-sensing receptor (CaR). Dietary
phosphate loading promotes secondary HPT, and
phosphate restriction prevents and arrests secondary HPT in CRF. This study examined the ability of
phosphate restriction to restore parathyroid CaR expression and function. Uremic rats fed a 1.2% P diet for 2 weeks developed secondary HPT with down-regulated CaR expression. Continuation on the 1.2% P diet for 2 more weeks worsened the secondary HPT and further decreased CaR, but switching the rats to a 0.2% P diet for 2 weeks normalized PTH, arrested parathyroid
hyperplasia, and restored CaR expression to normal. The
calcium-PTH relationship was abnormal in uremic rats fed a high
phosphate (HP) diet with a right-shifted
calcium set point but was corrected by 2 weeks of
phosphate restriction. A time course revealed that following the switch to a low
phosphate diet, PTH levels were normalized by day 1, and growth was arrested by day 2, but CaR expression was restored between days 7 and 14. We conclude that although
phosphate restriction restores CaR expression and function in parathyroid glands of uremic rats, it is a late event and not involved in the arrest of secondary HPT.