The dependency of calcium set point on basal plasma calcium in dialysis patients: a better explanation for the discrepancies regarding its link with PTH secretion than methodological differences.
BACKGROUND
The increase of calcium (Ca) set point in uremic hyperparathyroid patients and its decrease with calcitriol therapy are controversial. Besides methodological differences regarding the experimental protocol for obtaining the sigmoidal curve, mainly differences in definitions of maximal PTH (peak or steady value) and of calcium set point itself have been proposed for the discrepant conclusions. However, two other explanations are possible: the various aluminum load of the patients and the dependency of Ca set point upon the basal plasma ionized calcium (PCa).


METHODS
Therefore the Ca set point was measured in 2 groups of patients on maintenance dialysis never exposed to aluminum, one of 7 patients with normosecretion of PTH (NPT) and the other of 8 patients with hyperparathyroidism (HPT) before and after 3 intravenous administration of 4 microg of alfacalcidol in a week. The sigmoidal curve was established during a zero Ca dialysis, without Ca replacement for the first 90 minutes and with intravenous infusion of 41 mmoles of Ca during the 150 last minutes. The curvilinear decrease of PCa induced a peak of PTH followed by a decrease while PCa was still decreasing up to the 90th minute. Therefore PTHmax was taken both at the peak and at its lower value observed at the 90th minute (steady PTHmax). Experimental determinations of the Ca set point were made using both definitions of Brown and Felsenfeld and both PTHmax values. In basal conditions, while using any of the values given by the same calculation methodology, Ca set point was not different in NPT and HPT patients. After alfacalcidol, no change in plasma PTH nor in Ca set point was observed in HPT patients. In contrast, in NPT patients alfacalcidol induced a significant decrease of plasma PTH concentrations in association with an increase in basal PCa and in Ca set point, whatever the definitions of the latter and of PTHmax. Calcitriol induced changes in Ca set point and basal PCa were correlated.


CONCLUSIONS
1) In normocalcemic dialysis patients never exposed to aluminium hyperparathyroidism is not explained by an increased Ca set point 2) Calcitriol suppressive effect on PTH secretion is neither explained by a decrease in Ca set point. 3) Ca set point as measured in vivo does not reflect an intrinsic characteristic of the parathyroid glands since it varies with basal PCa. Better than methodological differences, this dependency may explain the discrepant conclusions between the various clinical investigations.
Hardy-Yverneau
P
P
Service de Néphrologie-Médecine Interne du CHU d'Amiens, France.
Shenouda
M
M
Moriniere
P
P
Legallais
C
C
Brazier
M
M
Achard
J
J
Fournier
A
A
D000535:Aluminum / Q000009:adverse effects; D002117:Calcitriol / Q000627:therapeutic use; D002118:Calcium / Q000008:administration & dosage / Q000097:blood* / Q000502:physiology / Q000627:therapeutic use; D002120:Calcium Channel Agonists / Q000627:therapeutic use; D005260:Female; D015312:Hemodialysis Solutions / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006887:Hydroxycholecalciferols / Q000627:therapeutic use; D006961:Hyperparathyroidism / Q000503:physiopathology / Q000628:therapy; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood / Q000378:metabolism*; D006435:Renal Dialysis; D013997:Time Factors; D014511:Uremia / Q000503:physiopathology / Q000628:therapy
D002120:Calcium Channel Agonists; D015312:Hemodialysis Solutions; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D000535:Aluminum; D002117:Calcitriol; D002118:Calcium; C008088:alfacalcidol