Parathyroid function as a determinant of the response to calcitriol treatment in the hemodialysis patient

Background. Bolus calcitriol (CTR) is used for the treatment of secondary h yperparathyroidism in dialysis patients. Although CTR treatment reduces par athyroid hormone (PTH) levels in many dialysis patients, a significant numb er fail to respond. Methods. To learn whether or not an analysis of parathyroid function could further illuminate the response to CTR, a PTH-calcium curve was performed b efore and after at least two months of CTR treatment in 50 hemodialysis pat ients with a predialysis intact PTH of greater than 300 pg/ml. Results. For the entire group (N = 50), CTR treatment resulted in a 24% red uction in predialysis (basal) PTH from 773 +/- 54 to 583 +/- 71 pg/ml (P < 0.001), whereas ionized calcium increased from 1.10 +/- 0.02 to 1.22 +/- 0. 02 mM (P < 0.001): however, maximal and minimal PTH did not change from pre -CTR values. Based on whether or not the basal PTH decreased by 40% or more during CTR treatment, patients were divided into responders (Rs, N = 25) a nd nonresponders (NRs, N = 25). Before CTR, the NR group was characterized by a greater basal (959 +/- 80 vs. 586 +/- 51 pg/ml, P < 0.001) and maximal (1899 +/- 170 vs. 1172 +/- 108 pg/ml, P < 0.001) PTH and serum phosphorus (6.14 +/- 0.25 vs. 5.14 +/- 0.34 mg/dl, P < 0.01). Logistical regression an alysis showed that the pre-CTR basal PTH was the most important predictor o f the post-CTR basal PTH. and a pre-CTR basal PTH of 750 pg/ml represented a 50% probability of a response. Basal PTH correlated with the ionized calc ium in the NR group (r = 0.59, P = 0.002) but not in the R group (r = 0.06, P = NS). In the R group, an inverse correlation was present between ionize d calcium and the basal/maximal PTH ratio, an indicator of whether calcium is suppressing basal PTH secretion relative to the maximal secretory capaci ty (maximal PTH) r = -0.55, P = 0.004; in the NR group, this correlation ap proached significance but was positive (r = 0.34, P = 0.09). After CTR trea tment, serum calcium increased in both groups, and despite marked differenc es in basal PTH (Rs, 197 +/- 25 vs. NRs, 969 +/- 85 pg/ml), an inverse corr elation between ionized calcium and basal/maximal PTH was present in both g roups (Rs, r = -0.61, P = 0.001, and NRs, r = -0.60, P = 0.001). Conclusions. (a) Dynamic testing of parathyroid function provided insights into the pathophysiology of PTH secretion in hemodialysis patients. (b) The magnitude of hyperparathyroidism was the most important predictor of the r esponse to CTR. (c) Before CTR treatment, PTH was sensitive to calcium in R s, and serum calcium was PTH driven in NRs, and (d) after the CTR-induced i ncrease in serum calcium, calcium suppressed basal PTH relative to maximal PTH in both groups.