Calcium-mediated parathyroid hormone suppression to assess progression of secondary hyperparathyroidism during treatment among incident dialysis patients.

Abstract

Parathyroid gland function is affected adversely by tissue hyperplasia and gland enlargement in hyperparathyroidism. We examined the effects of 2 treatment strategies on the progression of secondary hyperparathyroidism using measurements of the nonsuppressible component of calcium-regulated PTH secretion as an index of parathyroid mass. In this randomized, open-label study, subjects managed with hemodialysis for >3 but <12 months before entering the trial (mean, 7.2 months) who had baseline plasma PTH levels >300 pg/mL received cinacalcet and low-dose vitamin D sterols (Cin-D, n = 153) or larger, varying doses of calcitriol, or other vitamin D analogs (Flex-D, n = 151). Study drug doses were adjusted periodically based on PTH and serum total calcium determinations. The exploratory endpoint was calcium-regulated PTH release, assessed using a standardized PTH suppression test before and after 52 weeks of treatment and 4 weeks after withdrawing treatment. PTH and serum total calcium were measured before hemodialysis using high-calcium (3.5 mEq/L or 1.75 mmol/L) dialysate and after 150 and 180 minutes. Mean (95% confidence interval) nonsuppressible calcium-regulated PTH release at baseline did not differ between Cin-D, 33.4% (25.9%, 40.9%), and Flex-D, 28.1% (23.2%, 32.9%). Corresponding values after 52 weeks of treatment were 34.3% (29.7%, 38.9%) and 42.0% (32.7%, 51.3%), not significant, and did not change measurably in either group when reevaluated 4 weeks after treatments were withdrawn. Disease progression over 12 months was not documented using a PTH suppression test in this population. Calcium-mediated PTH suppression was maintained fully, however, in Cin-D despite reductions in serum total calcium concentration, whereas values did not increase in Flex-D despite substantial increases in serum calcium.