INTRAVENOUS 1,25(OH)(2)D THERAPY INCREASES THE INTACT PARATHYROID-HORMONE SECRETION SET-POINT IN HEMODIALYZED PATIENTS

We have studied the effect of intravenous calcitriol [1,25(OH)(2)D] th erapy (1 mu g at the end of each dialysis session) on parathyroid secr etory curves of hemodialyzed patients with near-normal basal intact (< 10 pmol/l, n = 7; NNBI) or elevated basal intact (> 10 pmol/l, n = 6; EBI) parathyroid hormone (PTH; iPTH) levels. These results were compa red with those obtained in matched normal individuals (N). Our main ob jective was to define the influence of intravenous 1,25(OH)(2)D therap y on the set point of iPTH stimulation in relation to the severity of secondary hyperparathyroidism. A complete parathyroid function was obt ained by CaCl2 and Na(2)EDTA infusions in 14 N and by modification of the dialysate calcium content in 13 hemodialyzed patients. Ionized cal cium (Ca2+) and iPTH were measured regularly during hypo- and hypercal cemia. Parathyroid secretory curves were derived from these data. Both groups of patients had lower basal Ca2+ (NNBI 1.16 +/- 0.05; EBI 1.10 +/- 0.03; N 1.25 +/- 0.04 mmol/l; p < 0.001) and higher basal iPTH (N NBI 6.3 +/- 2.5; EBI 49.2 +/- 39.5; N 2.5 +/- 0.8 pmol/l; p < 0.01) le vels than N with more extreme values in EBI than in NNBI patients (p < 0.001). NNBI patients had stimulated iPTH levels similar to N (18.4 /- 7.1 vs. 17.3 +/- 7.2 pmol/l), while these levels were markedly incr eased in EBI patients (80.7 +/- 46.0 pmol/l; p < 0.001). After 1,25(OH )(2)D therapy, Ca2+ increased to 1.16 +/- 0.03 mmol/l in EBI and norma lized in NNBI patients (1.25 +/- 0.07 mmol/l). Stimulated iPTH decreas ed by 30% in NNBI (p < 0.05) and by 21% in EBI patients (NS). These tw o factors contributed to a decrease in basal iPTH by 52% in NNBI (p < 0.05) and by 40% in EBI (p < 0.01). The set point of iPTH stimulation was lower than in N (1.18 +/- 0.04 mmol/l) and increased with intraven ous 1,25(OH)(2)D therapy from 1.09 +/- 0.03 to 1.16 +/- 0.05 mmol/l in NNBI (p < 0.05) and from 1.08 +/- 0.04 to 1.12 +/- 0.04 mmol/l in EBI patients (p < 0.05). The set points and changes in set point were cor related with basal Ca2+ (r = 0.56; p = 0.003) and changes in basal Ca2 + (r = 0.64; p = 0.04) observed before and during therapy. The startin g position of each patient on his secretory curve before and after 1,2 5(OH)(2)D therapy was inversely related to his starting Ca2+ concentra tion (n=26; r = -0.66; p = 0.0003). Taking this into account improved the relationship between Ca2+ concentration and the set point of iPTH stimulation by Ca2+ in a stepwise regression (R(2) = 0.62; p = 0.0003) . However, no correlation was found between set points and stimulated iPTH values. We concluded that 1,25(OH)(2)D therapy induced an increas e in the set point of PTH stimulation in hypocalcemic hemodialyzed pat ients related to a similar increase in basal Ca2+ concentration. This is in part related to the starting position of each patient on his sec retory curve which will affect his set point in relation to the hyster esis phenomenon in iPTH secretion. But the set point of PTH stimulatio n is also related to the basal ionized calcium concentration by mechan isms yet to be elucidated.