Nephrol Dial Transplant (2001) 16: 506-512
© 2001 European Renal Association-European Dialysis and Transplant Association
Failure of high doses of calcitriol and hypercalcaemia to induce apoptosis in hyperplastic parathyroid glands of azotaemic rats
1 Departments of Nephrology and 2 Pathology, Pontificia Universidad Católica de Chile, Santiago, Chile, 3 Department of Medicine, West Los Angeles VA Medical Center and UCLA, Los Angeles, California, USA
Background. Whether calcitriol administration, which is used to treat secondary hyperparathyroidism in dialysis patients, induces regression of parathyroid-gland hyperplasia remains a subject of interest and debate. If regression of the parathyroid gland were to occur, the presumed mechanism would be apoptosis. However, information on whether high doses of calcitriol can induce apoptosis of parathyroid cells in hyperplastic parathyroid glands is lacking. Consequently, high doses of calcitriol were given to azotaemic rats and the parathyroid glands were evaluated for apoptosis.
Methods. Rats were either sham-operated (two groups) or underwent a two-stage 5/6 nephrectomy (three groups). For the first 4 weeks, all rats were given 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, three of the five groups were given high doses of calcitriol (500 pmol/100 g body 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 diet; (ii) NRF+0.6% P+calcitriol; (iii) renal failure (RF)+0.6% P; (iv) RF+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 sacrifice, the respective serum calcium values in calcitriol-treated 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-treated 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 marked 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 apoptosis could be induced in azotaemic rats by the combination of high doses of calcitriol and severe hypercalcaemia despite the marked reduction in PTH levels that was observed.
Keywords: apoptosis; calcitriol; hypercalcaemia; parathyroid gland; parathyroid hormone; rat
Correspondence and offprint requests to: Dr Aquiles Jara, Department of Nephrology, Pontificia Universidad Católica de Chile, Marcoleta 345, Santiago, Chile.
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