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 hyperparathyroidism in dialysis patients. Although CTR treatment reduces parathyroid hormone (PTH) levels in many dialysis patients, a significant number 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 before and after at least two months of CTR treatment in 50 hemodialysis patients with a predialysis intact PTH of greater than 300 pg/ml.


RESULTS
For the entire group (N = 50), CTR treatment resulted in a 24% reduction 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) and 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 analysis showed that the pre-CTR basal PTH was the most important predictor of 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 calcium 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 ionized calcium and the basal/maximal PTH ratio, an indicator of whether calcium is suppressing basal PTH secretion relative to the maximal secretory capacity (maximal PTH) r = -0.55, P = 0.004; in the NR group, this correlation approached significance but was positive (r = 0.34, P = 0.09). After CTR treatment, serum calcium increased in both groups, and despite marked differences in basal PTH (Rs, 197 +/- 25 vs. NRs, 969 +/- 85 pg/ml), an inverse correlation between ionized calcium and basal/maximal PTH was present in both groups (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 response to CTR. (c) Before CTR treatment, PTH was sensitive to calcium in Rs, and serum calcium was PTH driven in NRs, and (d) after the CTR-induced increase in serum calcium, calcium suppressed basal PTH relative to maximal PTH in both groups.
Nephrology Services from the Hospital Universitario Reina Sofia, Cordoba, Spain. mrodriguez@sofia.hrs.sas.cica.es
M
M
Rodriguez
F
F
Caravaca
E
E
Fernandez
M J
MJ
Borrego
V
V
Lorenzo
J
J
Cubero
A
A
Martin-Malo
A
A
Betriu
A
A
Jimenez
A
A
Torres
A J
AJ
Felsenfeld
D002117:Calcitriol / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood; D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000187:drug effects* / Q000503:physiopathology*; D010281:Parathyroid Hormone / Q000097:blood; D006435:Renal Dialysis / Q000009:adverse effects*; D016896:Treatment Outcome
D002120:Calcium Channel Agonists; D010281:Parathyroid Hormone; D002117:Calcitriol; D002118:Calcium