Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1α-hydroxyvitamin D2) in dialysis patients with secondary hyperparathyroidism: A sequential comparison

Abstract

Most reports on the effectiveness and side effects of oral versus parenteral calcitriol or alfacalcidol in hemodialysis patients with secondary hyperparathyroidism show no advantage of parenteral treatment. The efficacy and safety of intravenous doxercalciferol (1alphaD(2)) were studied in hemodialysis patients with secondary hyperparathyroidism (plasma intact parathyroid hormone [iPTH]: range, 266 to 3,644 pg/mL; median, 707 pg/mL). These results were compared with those of a previous trial using intermittent oral 1alphaD(2); the same 70 patients were entered onto both trials, and 64 patients completed both trials per protocol. Twelve weeks of open-label treatment in both trials were preceded by identical 8-week washout periods. Degrees of iPTH suppression from baseline were similar in the two trials, with iPTH level reductions less than 50% in 89% and 78% of patients during oral and intravenous treatment, respectively. Grouping patients according to entry iPTH levels (<750 and >/=750 pg/mL) showed similar but more rapid iPTH suppression in the low-iPTH groups, whereas longer treatment and larger doses were required by the high-iPTH groups. Highest serum calcium levels averaged 9.82 +/- 0.14 and 9.67 +/- 0.11 mg/dL during oral and intravenous 1alphaD(2) treatment, respectively (P: = not significant [NS]). Prevalences of serum calcium levels greater than 11.2 mg/dL during oral and intravenous treatment were 3.62% and 0.86% of calcium measurements, respectively (P: < 0.001). Highest serum phosphorus levels during oral and intravenous treatment averaged 5.82 +/- 0.21 and 5.60 +/- 0.21 mg/dL, respectively (P: = NS). The percentage of increments in serum phosphorus levels during oral treatment exceeded that during intravenous treatment during 5 of 12 treatment weeks. Thus, intermittent oral and intravenous therapy with 1alphaD(2) reduced iPTH levels effectively and similarly, hypercalcemia was less frequent, and serum phosphorus levels increased less during intravenous than oral 1alphaD(2) therapy, suggesting that intravenous 1alphaD(2) therapy may be advantageous in patients prone to hypercalcemia or hyperphosphatemia.

Treatment of Secondary Hyperparathyroidism in CKD Patients with Cinacalcet and/or Vitamin D Derivatives

“…In contrast, active vitamin D sterols often induce hypercalcemia and/or hyperphosphatemia (83)(84)(85). The frequency of these side effects may be less with so-called nonhypercalcemic active vitamin D derivatives such as paricalcitol (92) or doxercalciferol (93), but it clearly has not been reduced to zero (94,95).…”

Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

“…Despite many years of clinical use, results from prospective clinical trials describing therapeutic responses to any vitamin D sterol among dialysis patients with SHPT lasting more than 13 mo are available from only six patients after 2 yr of follow-up (20). Sustained treatment with vitamin D alone often proves inadequate for dialysis patients with SHPT (7)(8)(9). Disturbances in calcium and phosphorus metabolism frequently disrupt therapy (10), rendering consistent biochemical control of the disorder difficult (8).…”

“…Sustained treatment with vitamin D alone often proves inadequate for dialysis patients with SHPT (7)(8)(9). Disturbances in calcium and phosphorus metabolism frequently disrupt therapy (10), rendering consistent biochemical control of the disorder difficult (8).…”

Efficacy of Cinacalcet for the Treatment of Secondary Hyperparathyroidism in CKD Patients on Peritoneal or Hemo Dialysis: The Middle-East Experience

“…Vitamin D sterols (calcitriol/ alphacalcidol) effectively reduced intact PTH levels but caused hypercalcemia and hyperphosphatemia as a result of increased calcium and phosphorous absorption from gastrointestinal tract [24]. Thus, hypercalcemia and hyperphosphatemia would be a contraindication for use of vitamin D sterols and thus, in our study vitamin D sterols were withheld in 11.5% of cases in cinacalcet group.…”

“…Poor control of mineral metabolism is also associated with a higher risk for calcification of the coronary arteries and aorta, increased arterial stiffness, cardiac valve calcification and death [5,8,24,25]. Raggi et al documented that hemodialysis patients with moderate to severe SHPT cinacalcet plus low-dose vitamin D sterols displayed attenuated vascular and cardiac valve calcification compared with those on flexible vitamin D therapy [26].…”