Evidence for adaptation of the entire PTH-calcium curve to sustained changes in the serum calcium in haemodialysis patients

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Abstract
BACKGROUND: Based on in vitro studies, the set point of calcium has often been considered to represent an intrinsic property of parathyroid gland function. However, in the dialysis patient, the serum calcium does not consistently reflect the magnitude of hyperparathyroidism; in addition, little information is available on whether the PTH-calcium curve is modified by sustained changes in the serum calcium. The present study in haemodialysis patients was designed to evaluate whether the set point of calcium and the dynamics of PTH secretion were modified by sustained changes in the serum calcium. METHODS: To accomplish the goal of the study and obtain a wide range of changes in the serum calcium, haemodialysis patients were dialysed with either a 1.75 mM (group I) or a 1.25 mM (group II) calcium dialysate for 2 weeks, and were then changed to a 1.25 mM (group I) or a 1.75 mM (group II) calcium dialysate for an additional 2 weeks. At the end of the first and second 2-week periods, low and high calcium studies were performed to obtain PTH-calcium curves. RESULTS: In group I, the serum ionized calcium decreased with the lower calcium dialysate (P < 0.02) and the set point of calcium was reduced (P < 0.02); in group II, the serum calcium did not change and the set point of calcium was not modified. When both groups were evaluated together, the delta serum calcium correlated directly with the delta set point of calcium (r = 0.87, P < 0.001) and inversely with the delta PTH (r = -0.73, P < 0.005); at the same time, an inverse correlation was observed between the delta PTH and the delta set point of calcium (r = -0.67, P < 0.01). Moreover, the delta serum calcium correlated with both the delta ratio of basal/maximal PTH (r = -0.71, P < 0.005) and the change in predialysis serum calcium necessary to maximally stimulate PTH (r = 0.84, P < 0.001); these latter two are indicators of the position of PTH along the PTH-calcium curve. Finally, in group I the entire PTH-calcium curve shifted to the left on the 1.25 mM calcium dialysate as compared with the 1.75 mM calcium dialysate. CONCLUSION: The findings of the present study indicate that: (1) the set point of calcium followed sustained changes in the serum calcium independently of PTH secretion, and (2) the parathyroid gland was able both to adjust the position of PTH secretion on the PTH-calcium curve and to adapt PTH secretion to the existing serum calcium concentration.

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