Paricalcitol and cinacalcet have disparate actions on parathyroid oxyphil cell content in patients with chronic kidney disease

The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting tha...

Full description

Saved in:
Bibliographic Details
Published in:Kidney international 2017-11, Vol.92 (5), p.1217-1222
Main Authors: Ritter, Cynthia, Miller, Brent, Coyne, Daniel W., Gupta, Diptesh, Zheng, Sijie, Brown, Alex J., Slatopolsky, Eduardo
Format: Article
Language:English
Subjects:
Adult
Calcimimetic Agents - pharmacology
Calcimimetic Agents - therapeutic use
Calcitriol - analogs & derivatives
calcium-sensing receptor
Cell Transdifferentiation - drug effects
chronic kidney disease
Cinacalcet Hydrochloride - pharmacology
Cinacalcet Hydrochloride - therapeutic use
Drug Therapy, Combination - methods
Ergocalciferols - pharmacology
Ergocalciferols - therapeutic use
Female
Humans
hyperparathyroidism
Hyperparathyroidism, Secondary - etiology
Hyperparathyroidism, Secondary - therapy
Hyperparathyroidism, Secondary - urine
Male
Middle Aged
Oxyphil Cells - drug effects
Parathyroid Glands - cytology
Parathyroid Glands - drug effects
Parathyroid Glands - metabolism
Parathyroid Glands - surgery
Parathyroidectomy
Receptors, Calcium-Sensing - metabolism
Renal Insufficiency, Chronic - complications
Renal Insufficiency, Chronic - drug therapy
Renal Insufficiency, Chronic - urine
Uremia - complications
Uremia - drug therapy
Uremia - urine
Vitamin D - analogs & derivatives
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The parathyroid oxyphil cell content increases in patients with chronic kidney disease (CKD), and even more in patients treated with the calcimimetic cinacalcet and/or calcitriol for hyperparathyroidism. Oxyphil cells have significantly more calcium-sensing receptors than chief cells, suggesting that the calcium-sensing receptor and calcimimetics are involved in the transdifferentiation of a chief cell to an oxyphil cell type. Here, we compared the effect of the vitamin D analog paricalcitol (a less calcemic analog of calcitriol) and/or cinacalcet on the oxyphil cell content in patients with CKD to further investigate the genesis of these cells. Parathyroid tissue from four normal individuals and 27 patients with CKD who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Prior to parathyroidectomy, patients had received the following treatment: seven with no treatment, seven with cinacalcet only, eight with paricalcitol only, or cinacalcet plus paricalcitol in five. Oxyphilic areas of parathyroid tissue, reported as the mean percent of total tissue area per patient, were normal, 1.03; no treatment, 5.3; cinacalcet, 26.7 (significant vs. no treatment); paricalcitol, 6.9 (significant vs. cinacalcet; not significant vs. no treatment); and cinacalcet plus paricalcitol, 12.7. Cinacalcet treatment leads to a significant increase in parathyroid oxyphil cell content but paricalcitol does not, reinforcing a role for the calcium-sensing receptor activation in the transdifferentiation of chief-to-oxyphil cell type. Thus, two conventional treatments for hyperparathyroidism have disparate effects on parathyroid composition, and perhaps function. This finding is provocative and may be useful when evaluating future drugs for hyperparathyroidism.
ISSN:0085-2538
1523-1755
DOI:10.1016/j.kint.2017.05.003