Reversal of secondary hyperparathyroidism by phosphate restriction restores parathyroid calcium‐sensing receptor expression and function

CS Ritter, DR Martin, Y Lu… - Journal of Bone and …, 2002 - academic.oup.com
CS Ritter, DR Martin, Y Lu, E Slatopolsky, AJ Brown
Journal of Bone and Mineral Research, 2002academic.oup.com
Abstract Secondary hyperparathyroidism (2° 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 2° HPT, and phosphate restriction prevents and arrests
2° 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 …
Abstract
Secondary hyperparathyroidism (2° 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 2° HPT, and phosphate restriction prevents and arrests 2° 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 2° HPT with down‐regulated CaR expression. Continuation on the 1.2% P diet for 2 more weeks worsened the 2° 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 2° HPT.
Oxford University Press