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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 x P product levels. The primary end points were efficacy (two consecutive iPTH decreases of >or=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 were 3.9 and 7.6 microg, 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 >or=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., ((c) 2007 S. Karger AG, Basel.)

Background: Secondary hyperparathyroidism is a common complication in children receiving hemodialysis. Active vitamin D is an effective therapy, but its use is often limited by hypercalcemia and increased calcium x phosphorus (Ca x P) product. Paricalcitol, a selective vitamin D receptor activator, causes less sustained hypercalcemia and increase in Ca x P product than calcitriol and has been used effectively in adult hemodialysis patients., Study Design: Double blind, placebo-controlled., Setting & Participants: Hemodialysis units and pediatric subjects receiving hemodialysis., Intervention: After a washout period of 2 to 6 weeks, 29 subjects aged 5 to 19 years received either paricalcitol or placebo for up to 12 weeks (0.04 mug/kg if initial intact parathyroid hormone [iPTH] level < 500 pg/mL [ng/L]; 0.08 mug/kg if initial iPTH level > 500 pg/mL [ng/L]). The dose was increased by 0.04 mug/kg every 2 weeks until there was a 30% decrease in iPTH level from baseline or calcium level greater than 11 mg/dL (>2.74 mmol/L) or Ca x P product greater than 75 mg(2)/dL(2) (>6.04 mmol(2)/L(2))., Outcomes & Measurements: Two consecutive 30% decreases from baseline in iPTH levels and safety of paricalcitol, including hypercalcemia and increase in Ca x P product., Results: 60% of the paricalcitol group had 2 consecutive 30% decreases from baseline iPTH levels compared with 21% in the placebo group (P = 0.06). The paricalcitol group had a mean decrease in iPTH level of 164 pg/mL (ng/L), whereas the placebo group had a mean increase of 238 pg/mL (ng/L; P = 0.03). There was no difference from baseline to final visit in calcium, phosphorus, or Ca x P product values in either group., Limitations: Low power to detect differences in safety between groups and a short-term study., Conclusion: Paricalcitol decreased iPTH levels in children receiving hemodialysis with no significant changes in serum calcium, phosphorus, or Ca x P product values during the course of the study.

Background: Intermittent dosing of calcitriol for secondary hyperparathyroidism (SHPT) has been associated with greater parathyroid hormone (PTH) reduction with fewer calcemic and phosphatemic effects than daily (QD) dosing., Methods: Secondary analyses of three randomized, double-blind, placebo-controlled multicenter studies in stage 3 and 4 chronic kidney disease (CKD) patients with SHPT were performed to compare three times per week (TIW) with QD dosing of paricalcitol. The pharmacokinetics of TIW and QD dosing of paricalcitol capsules were assessed in a separate group of healthy subjects., Results: Pharmacokinetics revealed similar steady state paricalcitol exposure between dosing regimens. In CKD patients, baseline data were similar between the TIW studies (n = 72, paricalcitol; n = 73, placebo) and QD studies (n = 35, paricalcitol; n = 40, placebo). Both dosing regimens resulted in similar efficacy (91%) for the primary end point of two consecutive > or = 30% decreases in intact PTH from baseline, but the QD regimen resulted in a greater percent reduction in intact PTH from baseline. The chances for developing increased serum calcium and phosphorus levels or Ca x P product were similar between paricalcitol and placebo groups for both treatment regimens. Furthermore, no difference in the risk for these elevations was detected between the TIW and QD regimens., Conclusions: QD dosing of paricalcitol capsules is as efficacious as TIW dosing in achieving the primary end point (2 consecutive > or = 30% reductions in PTH) in stage 3 and 4 CKD patients with SHPT. Moreover, the QD regimen had no significant effect on hypercalcemia, hyperphosphatemia or Ca x P product as compared with placebo or intermittent dosing., (Copyright 2006 S. Karger AG, Basel)

Background: Proteinuria is a marker of cardiovascular and renal disease in patients with chronic kidney disease (CKD), and reduction in proteinuria has been associated with improved cardiovascular and renal outcomes. While active vitamin D and its analogs have been shown to have renal protective effects in animals, these hormones have not been shown to reduce proteinuria in CKD patients., Methods: In three double-blind, randomized, placebo-controlled studies to evaluate the safety and efficacy of oral paricalcitol, 220 CKD stage 3 and 4 patients with secondary hyperparathyroidism (SHPT) were randomized to oral paricalcitol (N= 107, mean dose 9.5 microg/week) or placebo (N= 113) and followed for up to 24 weeks. In conjunction with other safety measures, proteinuria was measured by dipstick and read by an automated reader at the beginning and end of trial. We subsequently analyzed the dipstick data to evaluate the effect of paricalcitol on proteinuria., Results: At baseline, proteinuria was present in 57 patients randomized to oral paricalcitol and 61 patients randomized to placebo (NS). At the final visit, 29/57 (51%) of the paricalcitol patients compared to 15/61 (25%) placebo patients had reduction in proteinuria, P= 0.004 (odds for reduction in proteinuria 3.2 times greater for paricalcitol patients, 95% CI 1.5-6.9). For the patients who had both proteinuria at baseline and parathyroid hormone (PTH) suppression (end point defined as 2 consecutive > or =30% decreases in iPTH from baseline), 27/51 (53%) patients had a reduction in the proteinuria in the paricalcitol group and 0/7 (0%) had a reduction in proteinuria in the placebo group. Reduction of proteinuria favored patients on paricalcitol, regardless of age, sex, race, diabetes mellitus, hypertension, or use of therapies to block the renin-angiotensin-aldosterone system (RAAS)., Conclusion: Our results demonstrate that the reduction in proteinuria was associated with paricalcitol treatment, and the reduction in proteinuria was independent of concomitant use of agents that block the RAAS. Paricalcitol as a potential pharmacologic means of reducing proteinuria in CKD patients warrants further investigation.

Background: Abnormalities of serum calcium, phosphorous and intact parathyroid hormone (PTH) are associated with morbidity and mortality in haemodialysis patients. Pharmacologic parenteral vitamin D administration is used to correct these abnormalities; however, the relationship between vitamin D therapies and hospitalizations has never been addressed., Methods: Healthcare data from January 1999 to November 2001 were analysed for 11,443 adult haemodialysis patients who received at least 10 doses of vitamin D therapy. Multivariate models were used to evaluate the effects of vitamin D therapy on: (i) total number of hospitalizations, (ii) total number of hospital days and (iii) risk of first hospitalization after initiation of vitamin D therapy., Results: When compared with the calcitriol group, the paricalcitol group had a lower risk of first all-cause hospitalization (14% less likely, P<0.0001), fewer hospitalizations per year (0.642 fewer, P<0.001) and fewer hospital days per year (6.84 fewer, P<0.001). In the paricalcitol and calcitriol groups, respectively, 5.6 and 41.3% patients switched to another vitamin D compound. For those patients who started and remained on the same vitamin D product, paricalcitol-treated patients experienced 0.846 fewer hospitalizations per year and 9.17 fewer hospital days per year, P<0.001 for both. The paricalcitol group also had a lower risk of first PTH-related hospitalizations, fewer PTH-related annual hospitalizations and fewer days per year., Conclusion: Paricalcitol-treated patients experienced fewer hospitalizations and hospital days per year when compared with calcitriol-treated patients. Initiating vitamin D therapy with paricalcitol may result in overall savings of approximately 7600-11,000 US dollars per patient per year. A randomized, controlled, blinded study would be valuable in confirming and understanding these results.