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Single-dose oral calcitriol and changes of plasma 1,84iPTH in uremic children
G Klaus1, H Schmidt-Gayk, H J Roth
1Division of Pediatric Nephrology, University of Heidelberg, Germany.
Insights
Oral calcitriol effectively lowers parathyroid hormone (PTH) in children with chronic kidney disease for up to 72 hours. Individual responses vary, suggesting other factors influence calcitriol
Area of Science:
- Pediatric Nephrology
- Endocrinology
- Pharmacology
Background:
- Chronic kidney disease (CKD) often leads to secondary hyperparathyroidism.
- Intravenous and oral calcitriol (1,25(OH)2D3) pulse therapy are used to manage elevated intact parathyroid hormone (iPTH).
- The mechanisms behind the prolonged efficacy of intermittent calcitriol administration require further investigation.
Purpose of the Study:
- To investigate the pharmacokinetics of oral calcitriol and its effect on intact parathyroid hormone (iPTH) levels in children with advanced renal failure.
- To determine the duration of the iPTH suppressive effect after oral calcitriol administration.
- To explore factors influencing the interindividual variability in iPTH suppression.
Main Methods:
- A study involving 10 children with advanced renal failure and elevated baseline iPTH.
- Administration of a standard oral dose of calcitriol (2 micrograms).
- Monitoring of serum 1,25(OH)2D3 and iPTH concentrations over 72 hours, along with assessment of baseline characteristics.
Main Results:
- Oral calcitriol administration led to a significant increase in serum 1,25(OH)2D3 levels, peaking at 6 hours and returning to baseline by 48 hours.
- Serum iPTH concentrations were significantly suppressed between 6 and 72 hours post-administration, with a median maximal decrease of 51.4%.
- The degree of iPTH suppression was dependent on baseline iPTH levels but not on calcitriol pharmacokinetics, body surface area, or changes in ionized calcium.
Conclusions:
- Oral calcitriol exerts a prolonged (up to 72 hours) suppressive effect on iPTH in pediatric uremic patients.
- The significant interindividual variation in iPTH suppression is not explained by calcitriol pharmacokinetics alone.
- Additional unidentified factors likely play a crucial role in modulating the iPTH response to calcitriol in CKD patients.
Abstract:
Both intravenous and oral 1,25(OH)2 D3 pulse therapy are effective in decreasing iPTH in patients with chronic renal failure. In order to understand why intermittent application of calcitriol is effective, we investigated 10 children with advanced renal failure (4 female, 6 male; median age 6.5 [3-16] years; body surface area 0.58-1.57m2; CCR 7 [5-47] mL/min/1.73m2) with elevated baseline concentrations of 1,84iPTH (median 63.5 [9.4-300] pmol/L). After a standard dose of 2 micrograms calcitriol per os (equal to 1.27-3.45 micrograms/m2), serum 1,25(OH)2D3 concentrations increased. The peak concentration occurred after 6 h (3-12), and 1,25(OH)2D3 serum levels returned to baseline by 48 h. 1,84iPTH concentrations were significantly suppressed by 6-72 h. The median maximal decrease was 51.4% of baseline (22.3%-74%). The decrement was a function of baseline 1,84iPTH, but not of 1,25(OH)2D3 serum peak concentration, area under the curve, body surface area, or change in ionized serum calcium. We conclude: (i) oral 1,25(OH)2D3 has a prolonged (up to 72 h) suppressive effect on 1,84iPTH concentrations in uremic patients, and (ii) the wide interindividual variation in suppression of 1,84iPTH was not explained by the kinetics of 1,25(OH)2D3 concentration, which implies that additional factors influence the 1,84iPTH response to 1,25(OH)2D3.