Early Response of the Parathyroid Gland to Withdrawal of a Calcimimetic Compound in Uremic Rats.

We examined the response of parathyroid glands to withdrawal of cinacalcet in uremic rats. Uremic rats were fed a high phosphate diet to develop secondary hyperparathyroidism (SHPT) and then divided into groups treated with vehicle (UC), cinacalcet (Cina), and cinacalcet and maxacalcitol (Maxa), a vitamin D receptor activator (VDRA) (Cina+Maxa). After 2 weeks treatment, vehicle and cinacalcet were withdrawn, while Maxa was continued. Rats were analyzed immediately (day 0) and 7 days (day 7) after withdrawal. The Cina and Cina+Maxa had significantly lower PTH than the UC on day 0, but PTH in the Cina reached UC levels on day 7. On day 0, there were significantly more proliferating cell nuclear antigen (PCNA)-positive cells in the UC compared with normal controls, and this increase was significantly suppressed in the Cina and Cina+Maxa. On day 7, the Cina, but not the Cina+Maxa, showed a significant increase in PCNA-positive cells compared with the UC. This increase was related to parathyroid cell diameter regression to UC levels, while combination maintained diameter suppression. These results suggest that parathyroid growth activity is stimulated by cinacalcet withdrawal, although exacerbation of PTH elevation is not induced. Continuous administration of cinacalcet may be necessary for better control of SHPT. Simultaneous use of a VDRA may be preferable in the timing of cinacalcet withdrawal. PMID: 31961714 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research