Oral Paricalcitol for the Treatment of Secondary Hyperparathyroidism in Patients on Hemodialysis or Peritoneal Dialysis

Abstract

Background/Aims: Secondary hyperparathyroidism is a common complication of chronic kidney disease, resulting from inactivation of vitamin D receptor signaling and phosphate retention. Selective activation of vitamin D receptors with intravenous paricalcitol significantly reduced parathyroid hormone (PTH) levels with no significant hypercalcemia or hyperphosphatemia in predialysis and hemodialysis (HD) patients. This study investigates the effects of oral paricalcitol to reduce PTH in patients receiving chronic HD and peritoneal dialysis (PD). Methods: Eighty-eight patients were randomized in double-blind fashion to receive paricalcitol or placebo for 12 weeks. The dose of the study drug was adjusted weekly using the previous week’s intact PTH (iPTH) level as well as calcium and Ca × P product levels. The primary end points were efficacy (two consecutive iPTH decreases of ≧30%) and safety (two consecutive calcium measurements >11.0 mg/dl). Markers of biochemical bone activity were followed. Results: Demographic characteristics were similar between treatment groups. The mean paricalcitol doses (three times a week) over the entire treatment period for subjects with baseline iPTH ≤500 pg/ml and iPTH >500 pg/ml were 3.9 and 7.6 µg, respectively. A statistically significant decrease in iPTH was seen after week 1, with a mean 30% reduction occurring by week 3. A significantly greater proportion of both HD and PD paricalcitol subjects [83% (33/40) and 100% (18/18), respectively] achieved two consecutive ≧30% decreases in iPTH. The treatment groups were not statistically different in regard to the hypercalcemia safety end point. Phosphate binder use and mean serum phosphorus levels were not different between the treatment groups. The markers of bone activity improved in the treated subjects and worsened in those on placebo. Conclusion: Paricalcitol provides a rapid and sustained reduction of PTH in both HD and PD patients with minimal effect on serum calcium and phosphorus and no significant difference in adverse events as compared with placebo.

Efficacy and Safety of Paricalcitol Therapy for Chronic Kidney Disease

“…After discarding a number of duplicates retrieved by individual searches and reviewing all titles and abstracts, many studies were excluded because they were not RCTs, did not investigate any of the outcomes of interest to this study, or were animal or basic research studies or review articles. Overall, this analysis included nine trials that enrolled a total of 832 patients (9,(19)(20)(21)(22)(23)(24)(25)(26)(27) (Figure 1). Of the 10 included articles, those by Coyne et al (19) and Agarwal et al (25) were from the same clinical trials.…”

“…Five studies assessed PTH (defined as reaching at least a 30% reduction from the maximum baseline at the end of treatment) in a total of 563 patients (19,(21)(22)(23)(24). Two hundred and ninety-nine patients were assigned to the treatment groups and 264 patients were assigned to the control groups.…”

“…Five studies involving 644 patients have been published on the effect of paricalcitol therapy on serum Ca levels in patients with CKD (9,19,20,22,24). Three-hundred and ninety-four patients were assigned to the treatment groups and 250 patients were assigned to the placebo groups.…”

“…Only one study (21) reported end of treatment serum phosphorus. Five of nine studies reported no effects on serum phosphorus after paricalcitol therapy and thus were not in a extractable format for this metaanalysis (20)(21)(22)(23)(24).…”

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

“…Exogenous administration of vitamin D receptor activators (VDRAs), such as calcitriol or the analogs paricalcitol, doxercalciferol, and alfacalcidol, suppresses PTH levels but can increase serum calcium and phosphorus (3)(4)(5). Major renal guidelines recommend use of active vitamin D for SHPT in stages 3-4 CKD, but comparison of different VDRAs in this population has been limited (6)(7)(8).…”