Failure of high doses of calcitriol and hypercalcaemia to induce apoptosisin hyperplastic parathyroid glands of azotaemic rats

Background. Whether calcitriol administration, which is used to treat secon dary hyperparathyroidism in dialysis patients, induces regression of parath yroid-gland hyperplasia remains a subject of interest and debate. If regres sion of the parathyroid gland were to occur, the presumed mechanism would b e apoptosis. However, information on whether high doses of calcitriol can i nduce apoptosis of parathyroid cells in hyperplastic parathyroid glands is lacking. Consequently, high doses of calcitriol were given to azotaemic rat s and the parathyroid glands were evaluated for apoptosis. Methods. Rats were either sham-operated (two groups) or underwent a two-sta ge 5/6 nephrectomy (three groups). For the first 4 weeks, all rats were giv en a high (1.2%) phosphorus (P) diet to stimulate parathyroid gland growth and then were changed to a normal (0.6%) P diet for 2 weeks. At week 7, thr ee of the five groups were given high doses of calcitriol (500 pmol/100 g b ody weight) intraperitoneally every 24 h during 72 h before sacrifice. The five groups during week 7 were: (i) normal renal function (NRF) + 0.6% P di et, (ii) NRF + 0.6% P + calcitriol; (iii) renal failure (RF)+0.6% P; (iv) R F+1.2% P+calcitriol; and (v) RF+0.6% P+calcitriol. Parathyroid glands were removed at sacrifice and the TUNEL stain was performed to detect apoptosis. Results, At sacrificer the respective serum calcium values in calcitriol-tr eated groups (groups 2, 4, and 5) were 15.52+/-0.26, 13.41+/-0.39 and 15.12 +/-0.32 mg/dl. In group 3, PTH was 178 +/- 42 pg/ml, but in calcitriol-trea ted groups, PTH values were suppressed, 8+/-1 (group 2), 12 +/- 2 (group 4) , and 7 +/- 1 pg/ml (group 5). Despite, the severe hypercalcaemia and marke d PTH suppression in calcitriol-treated groups, the percentage of apoptotic cells in the parathyroid glands was very low (range 0.08+/-0.04 to 0.25+/- 0.20%) and not different among the five groups. Conclusions. We found no evidence in hyperplastic parathyroid glands that a poptosis could be induced in azotaemic rats by the combination of high dose s of calcitriol and severe hypercalcaemia despite the marked reduction in P TH levels that was observed.