Differential Effects of Paricalcitol and Calcitriol on Intestinal Calcium Absorption in Hemodialysis Patients

Abstract

Background/Aims: Increased parathyroid activity associated with chronic kidney disease is often managed with calcitriol, which can elevate serum calcium (Ca) by increasing bone resorption and intestinal absorption, whereas paricalcitol promotes less bone resorption. This study compared intestinal Ca absorption in hemodialysis patients treated with calcitriol versus paricalcitol (dose ratio 1:3). Methods: Patients (n = 22) aged ≧20 years, on maintenance hemodialysis for ≧2 months with intact parathyroid hormone (iPTH) levels of >200 pg/ml were enrolled in a single-center, double-blind, active-controlled, randomized, crossover trial. Mean fractional intestinal Ca absorption (±SE) was measured by the single-tracer method (⁴²Ca) and evaluated with an analysis of variance crossover model. Results: Mean fractional intestinal Ca absorption was significantly lower after paricalcitol (0.135 ± 0.006) versus calcitriol treatment (0.158 ± 0.006, p = 0.022), a 0.023 difference in absolute Ca absorption fraction. Overall Ca absorption was low in the study population, indicating that regulation of Ca absorption may be dysfunctional. There were no significant differences in serum PTH, Ca, phosphorus (P), or Ca × P. Conclusion: Overall, paricalcitol-treated patients absorbed ∼14% less Ca compared with calcitriol-treated patients with similar effects on PTH. In hemodialysis patients, paricalcitol may provide a benefit by lowering the Ca available for removal by dialysis and/or for deposit in bone or soft tissues.

Calcium Absorption Response to Cholecalciferol Supplementation in Hemodialysis

“…Net absorption, taking into account both absorption and calcium loss, results in a net absorption of ;10% in healthy persons. In this study and previous studies of dialysis patients (27), we see percent calcium absorption values that are very low, and we see no response to vitamin D or doxercalciferol. The most probable interpretation is a defect in the mucosal response to vitamin D.…”

“…To put this finding into perspective, healthy persons absorb ;34% of the calcium load in these conditions (23). In one older study of renal disease, calcitriol increased calcium absorption in patients with chronic renal disease on hemodialysis (9), but this effect was not reproduced in a recent study comparing calcitriol with paricalcitol (27). Although calcitriol is clearly associated with hypercalcemia in dialysis patients, it cannot be assumed this result is a result of increased calcium absorption.…”

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

“…Also in chronic hemodialysis patients with SHPT paricalcitol intravenous therapy seemed to be superior compared with calcitriol therapy in a single-center randomized open label study (2). Moreover, paricalcitol has a small effect on intestinal calcium absorption compared with calcitriol in hemodialysis patients (273). were 5.4 Ϯ 1.10 to 5.9 Ϯ 1.55 mg/dl.…”

A Randomized Multicenter Trial of Paricalcitol versus Calcitriol for Secondary Hyperparathyroidism in Stages 3–4 CKD

“…Crossover trials of these agents in hemodialysis patients have also demonstrated less intestinal calcium absorption and less stimulation of bone resorption with paricalcitol compared with calcitriol (12,13). These differences are thought to be the result of less activation of the intestinal and bone VDRs by paricalcitol.…”