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Abstract

We appreciate the opportunity to respond and expand on the information provided in our original report.1Coyne D. Acharya M. Qui P. et al.Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD.Am J Kidney Dis. 2006; 47: 263-276Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar As mentioned there, a small mean increase (0.09 ± 0.04 mg/dL [0.02 ± 0.01 mmol/L]) in serum calcium level was observed in the paricalcitol group compared with a small mean decrease (−0.03 ± 0.04 mg/dL [−0.01 ± 0.01 mmol/L]) in the placebo group. The low serum calcium level observed in the paricalcitol group was discussed1Coyne D. Acharya M. Qui P. et al.Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD.Am J Kidney Dis. 2006; 47: 263-276Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar and is a component of the disease state observed, to a greater magnitude, in other studies.2Coburn J.W. Maung H.M. Elangovan L. et al.Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4.Am J Kidney Dis. 2004; 43: 877-890Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar Ranges were provided in the text to supplement Fig 3.1Coyne D. Acharya M. Qui P. et al.Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD.Am J Kidney Dis. 2006; 47: 263-276Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar These data on changes in serum calcium and phosphorus levels support “minimal or no impact” of paricalcitol, especially compared with other treatments for secondary hyperparathyroidism. A double-blind trial of calcitriol increased serum calcium levels by 8.7% after 32 weeks.3Nordal K.P. Dahl E. Halse J. Attramadal A. Flatmark A. Long-term low-dose calcitriol treatment in predialysis chronic renal failure Can it prevent hyperparathyroid bone disease?.Nephrol Dial Transplant. 1995; 10: 203-206PubMed Google Scholar Doxercalciferol increased serum calcium levels by 5% in a study of similar design to ours.2Coburn J.W. Maung H.M. Elangovan L. et al.Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4.Am J Kidney Dis. 2004; 43: 877-890Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar Calcium acetate (9 tablets in divided doses with meals) increased serum calcium levels 4.8% ± 1.6% after 8 weeks, with even a single tablet increasing serum calcium level by 2.5%.4Phelps K.R. Stern M. Slingerland A. Heravi M. Strogatz D.S. Haqqie S.S. Metabolic and skeletal effects of low and high doses of calcium acetate in patients with preterminal chronic renal failure.Am J Nephrol. 2002; 22: 445-454Crossref PubMed Scopus (6) Google Scholar Cinacalcet decreased serum calcium levels by 7% after 18 weeks and increased calcium-phosphorus product (6.7%) and phosphorus levels (∼14%), with mean phosphorus level greater than 4.5 mg/dL (>1.45 mmol/L) through most of the study.5Charytan C. Coburn J.W. Chonchol M. et al.Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis.Am J Kidney Dis. 2005; 46: 58-67Abstract Full Text Full Text PDF PubMed Scopus (125) Google ScholarA meta-analysis is unwarranted and would be less informative because comparing individual data provides a more rigorous assessment of treatment effect. Individual data can be used because the 3 studies were performed simultaneously, with the same population and design (except for dosing), and yielded similar results (Table 1).Table 1Parathyroid Hormone Reduction Following Daily or Thrice Weekly DosingStudySubjects Achieving (%) PTH Reduction End PointSubjects Achieving (%) Hypercalcemia End PointParicalcitolPlaceboParicalcitolPlaceboA (TIW)33 (92%)4 (12%)1 (3%)0 (0%)B (TIW)29 (91%)6 (17%)1 (3%)0 (0%)C (QD)30 (91%)4 (11%)0 (0%)0 (0%)Abbreviations: PTH, parathyroid hormone; TIW, 3 times weekly; QD, daily. Open table in a new tab Comparisons of the safety, efficacy, and pharmacokinetics of paricalcitol capsules between the 2 dosing regimens also were similar.6Abboud H. Coyne D. Smolenski O. et al.A comparison of dosing regimens of paricalcitol capsule for the treatment of secondary hyperparathyroidism in CKD stages 3 and 4.Am J Nephrol. 2006; 26: 105-114Crossref PubMed Scopus (18) Google Scholar Notably, the published phase 3 cinacalcet data combined patients from 2 studies.7Block G.A. Martin K.J. de Francisco A.L. et al.Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.N Engl J Med. 2004; 350: 1516-1525Crossref PubMed Scopus (937) Google ScholarWe appreciate the opportunity to elaborate on the notable responses to paricalcitol capsules and compare and contrast with alternative secondary hyperparathyroidism therapies. ALL LETTERS TO THE EDITOR MUST BE SUBMITTED ONLINE VIA EDITORIAL MAN-AGER (http://ajkd.edmgr.com). Letters should be in response to an AJKD article, and that article should have appeared no more than 6 months previously. The title must be different from that of the original article. Letters must not exceed 250 words (excluding references, maximum number 10) and contain no more than 1 figure or table. Letters are subject to editing and abridgment without notice and there is no guarantee that your letter will be published. Submitting the letter constitutes your permission for its publication in any current or subsequent issue or edition of AJKD, in any form or media, now known or hereafter developed. We appreciate the opportunity to respond and expand on the information provided in our original report.1Coyne D. Acharya M. Qui P. et al.Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD.Am J Kidney Dis. 2006; 47: 263-276Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar As mentioned there, a small mean increase (0.09 ± 0.04 mg/dL [0.02 ± 0.01 mmol/L]) in serum calcium level was observed in the paricalcitol group compared with a small mean decrease (−0.03 ± 0.04 mg/dL [−0.01 ± 0.01 mmol/L]) in the placebo group. The low serum calcium level observed in the paricalcitol group was discussed1Coyne D. Acharya M. Qui P. et al.Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD.Am J Kidney Dis. 2006; 47: 263-276Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar and is a component of the disease state observed, to a greater magnitude, in other studies.2Coburn J.W. Maung H.M. Elangovan L. et al.Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4.Am J Kidney Dis. 2004; 43: 877-890Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar Ranges were provided in the text to supplement Fig 3.1Coyne D. Acharya M. Qui P. et al.Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD.Am J Kidney Dis. 2006; 47: 263-276Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar These data on changes in serum calcium and phosphorus levels support “minimal or no impact” of paricalcitol, especially compared with other treatments for secondary hyperparathyroidism. A double-blind trial of calcitriol increased serum calcium levels by 8.7% after 32 weeks.3Nordal K.P. Dahl E. Halse J. Attramadal A. Flatmark A. Long-term low-dose calcitriol treatment in predialysis chronic renal failure Can it prevent hyperparathyroid bone disease?.Nephrol Dial Transplant. 1995; 10: 203-206PubMed Google Scholar Doxercalciferol increased serum calcium levels by 5% in a study of similar design to ours.2Coburn J.W. Maung H.M. Elangovan L. et al.Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4.Am J Kidney Dis. 2004; 43: 877-890Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar Calcium acetate (9 tablets in divided doses with meals) increased serum calcium levels 4.8% ± 1.6% after 8 weeks, with even a single tablet increasing serum calcium level by 2.5%.4Phelps K.R. Stern M. Slingerland A. Heravi M. Strogatz D.S. Haqqie S.S. Metabolic and skeletal effects of low and high doses of calcium acetate in patients with preterminal chronic renal failure.Am J Nephrol. 2002; 22: 445-454Crossref PubMed Scopus (6) Google Scholar Cinacalcet decreased serum calcium levels by 7% after 18 weeks and increased calcium-phosphorus product (6.7%) and phosphorus levels (∼14%), with mean phosphorus level greater than 4.5 mg/dL (>1.45 mmol/L) through most of the study.5Charytan C. Coburn J.W. Chonchol M. et al.Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis.Am J Kidney Dis. 2005; 46: 58-67Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar A meta-analysis is unwarranted and would be less informative because comparing individual data provides a more rigorous assessment of treatment effect. Individual data can be used because the 3 studies were performed simultaneously, with the same population and design (except for dosing), and yielded similar results (Table 1). Abbreviations: PTH, parathyroid hormone; TIW, 3 times weekly; QD, daily. Comparisons of the safety, efficacy, and pharmacokinetics of paricalcitol capsules between the 2 dosing regimens also were similar.6Abboud H. Coyne D. Smolenski O. et al.A comparison of dosing regimens of paricalcitol capsule for the treatment of secondary hyperparathyroidism in CKD stages 3 and 4.Am J Nephrol. 2006; 26: 105-114Crossref PubMed Scopus (18) Google Scholar Notably, the published phase 3 cinacalcet data combined patients from 2 studies.7Block G.A. Martin K.J. de Francisco A.L. et al.Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.N Engl J Med. 2004; 350: 1516-1525Crossref PubMed Scopus (937) Google Scholar We appreciate the opportunity to elaborate on the notable responses to paricalcitol capsules and compare and contrast with alternative secondary hyperparathyroidism therapies. ALL LETTERS TO THE EDITOR MUST BE SUBMITTED ONLINE VIA EDITORIAL MAN-AGER (http://ajkd.edmgr.com). Letters should be in response to an AJKD article, and that article should have appeared no more than 6 months previously. The title must be different from that of the original article. Letters must not exceed 250 words (excluding references, maximum number 10) and contain no more than 1 figure or table. Letters are subject to editing and abridgment without notice and there is no guarantee that your letter will be published. Submitting the letter constitutes your permission for its publication in any current or subsequent issue or edition of AJKD, in any form or media, now known or hereafter developed. ALL LETTERS TO THE EDITOR MUST BE SUBMITTED ONLINE VIA EDITORIAL MAN-AGER (http://ajkd.edmgr.com). Letters should be in response to an AJKD article, and that article should have appeared no more than 6 months previously. The title must be different from that of the original article. Letters must not exceed 250 words (excluding references, maximum number 10) and contain no more than 1 figure or table. Letters are subject to editing and abridgment without notice and there is no guarantee that your letter will be published. Submitting the letter constitutes your permission for its publication in any current or subsequent issue or edition of AJKD, in any form or media, now known or hereafter developed. ALL LETTERS TO THE EDITOR MUST BE SUBMITTED ONLINE VIA EDITORIAL MAN-AGER (http://ajkd.edmgr.com). Letters should be in response to an AJKD article, and that article should have appeared no more than 6 months previously. The title must be different from that of the original article. Letters must not exceed 250 words (excluding references, maximum number 10) and contain no more than 1 figure or table. Letters are subject to editing and abridgment without notice and there is no guarantee that your letter will be published. Submitting the letter constitutes your permission for its publication in any current or subsequent issue or edition of AJKD, in any form or media, now known or hereafter developed. Paricalcitol Capsule for the Treatment of Secondary Hyperparathyroidism in Stages 3 and 4 CKDAmerican Journal of Kidney DiseasesVol. 47Issue 2PreviewBackground: The safety and efficacy of paricalcitol injection have been well established for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stage 5. The capsule form of paricalcitol was developed to provide a convenient dosage form for patients with stages 3 and 4 CKD. Methods: Three randomized, placebo-controlled, phase-3 trials were conducted in patients with stages 3 and 4 CKD with SHPT. Enrollment criteria included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m2 (0.25 and 1.00 mL/s/1.73 m2), an average of 2 consecutive intact parathyroid hormone (iPTH) levels greater than 150 pg/mL (ng/L), 2 consecutive serum calcium levels between 8.0 and 10.0 mg/dL (2.00 and 2.50 mmol/L), and 2 consecutive serum phosphorus levels of 5.2 mg/dL or less (≤1.68 mmol/L). Full-Text PDF Paricalcitol for Treatment of Secondary Hyperparathyroidism in CKD PatientsAmerican Journal of Kidney DiseasesVol. 47Issue 6PreviewIn their recent report, Coyne et al1 combine 3 randomized phase 3 trials in patients with chronic kidney disease stages 3 to 4 aimed at examining the efficacy of oral paricalcitol. They concluded that paricalcitol capsules decreased serum intact parathyroid hormone levels effectively, with minimal or no impact on serum calcium levels. Full-Text PDF