Tags

Type your tag names separated by a space and hit enter

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism.
Clin J Am Soc Nephrol. 2015 Jun 05; 10(6):1021-30.CJ

Abstract

BACKGROUND AND OBJECTIVES

Cinacalcet and vitamin D are often combined to treat secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects on fibroblast growth factor-23 (FGF-23) concentrations in patients on hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during treatment of SHPT are evaluated.

DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS

A multicenter, randomized, open-label study to compare the efficacy of cinacalcet versus traditional vitamin D therapy for management of secondary hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a prospective, phase 4, multicenter, randomized, open-label study conducted globally. Participants (n=312) were randomized 1:1 to cinacalcet (n=155) or vitamin D analog (n=157) for 52 weeks. Levels of FGF-23 were measured at baseline and weeks 20 and 52. The absolute and percentage changes from baseline in plasma FGF-23, parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and calcium-phosphorus product (Ca×P) were assessed. Correlations and logistic regression were used to explore relationships between changes in FGF-23 and changes in PTH, Ca, P, and Ca×P from baseline to week 52 by treatment arm.

RESULTS

Median (quartiles 1, 3) decrease in FGF-23 concentrations was observed in the cinacalcet arm (-40%; -63%, 16%) compared with median increase in the vitamin D analog arm (47%; 0%, 132%) at week 52 (P<0.001). Changes in FGF-23 in both arms were unrelated to changes in PTH (cinacalcet: r=0.17, P=0.11; vitamin D analog: r=-0.04, P=0.70). Changes in FGF-23 in the vitamin D analog but not the cinacalcet arm were correlated with changes in Ca (cinacalcet: r=0.11, P=0.30; vitamin D analog: r=0.32, P<0.01) and P (cinacalcet: r=0.19, P=0.07; vitamin D analog: r=0.49, P<0.001). Changes in FGF-23 were correlated with changes in Ca×P in both arms (cinacalcet: r=0.26, P=0.01; vitamin D analog: r=0.57, P<0.001). Independent of treatment arm, participants with reductions in P or Ca×P were significantly more likely to show reductions in FGF-23.

CONCLUSIONS

During treatment of SHPT, cinacalcet use was associated with a decrease in FGF-23 concentrations, whereas vitamin D analogs were associated with an increase. The divergent effects of these treatments on FGF-23 seem to be independent of modification of PTH. It is possible that effects of cinacalcet and vitamin D analogs on FGF-23 may be mediated indirectly by other effects on bone and mineral metabolism.

Authors+Show Affiliations

Division of Nephrology and Hypertension, NorthShore University HealthSystem, Evanston, Illinois; ssprague@northshore.org.Division of Nephrology, Hennepin County Medical Center, Minneapolis, Minnesota;Fresenius Medical Care, St. Petersburg, Russia;Division of Nephrology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada;Columbia Nephrology Associates, Columbia, South Carolina; and.Clinical Research, Amgen Inc., Thousand Oaks, California.Clinical Research, Amgen Inc., Thousand Oaks, California.Clinical Research, Amgen Inc., Thousand Oaks, California.

Pub Type(s)

Clinical Trial, Phase IV
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25873267

Citation

Sprague, Stuart M., et al. "Effect of Cinacalcet and Vitamin D Analogs On Fibroblast Growth Factor-23 During the Treatment of Secondary Hyperparathyroidism." Clinical Journal of the American Society of Nephrology : CJASN, vol. 10, no. 6, 2015, pp. 1021-30.
Sprague SM, Wetmore JB, Gurevich K, et al. Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism. Clin J Am Soc Nephrol. 2015;10(6):1021-30.
Sprague, S. M., Wetmore, J. B., Gurevich, K., Da Roza, G., Buerkert, J., Reiner, M., Goodman, W., & Cooper, K. (2015). Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism. Clinical Journal of the American Society of Nephrology : CJASN, 10(6), 1021-30. https://doi.org/10.2215/CJN.03270314
Sprague SM, et al. Effect of Cinacalcet and Vitamin D Analogs On Fibroblast Growth Factor-23 During the Treatment of Secondary Hyperparathyroidism. Clin J Am Soc Nephrol. 2015 Jun 5;10(6):1021-30. PubMed PMID: 25873267.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism. AU - Sprague,Stuart M, AU - Wetmore,James B, AU - Gurevich,Konstantin, AU - Da Roza,Gerald, AU - Buerkert,John, AU - Reiner,Maureen, AU - Goodman,William, AU - Cooper,Kerry, Y1 - 2015/04/14/ PY - 2014/03/03/received PY - 2014/12/26/accepted PY - 2015/4/16/entrez PY - 2015/4/16/pubmed PY - 2016/3/10/medline KW - ESRD KW - clinical nephrology KW - dialysis KW - hyperparathyroidism SP - 1021 EP - 30 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 10 IS - 6 N2 - BACKGROUND AND OBJECTIVES: Cinacalcet and vitamin D are often combined to treat secondary hyperparathyroidism (SHPT) in patients on dialysis. Independent effects on fibroblast growth factor-23 (FGF-23) concentrations in patients on hemodialysis administered cinacalcet or vitamin D analogs as monotherapies during treatment of SHPT are evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A multicenter, randomized, open-label study to compare the efficacy of cinacalcet versus traditional vitamin D therapy for management of secondary hyperparathyroidism among subjects undergoing hemodialysis (PARADIGM) was a prospective, phase 4, multicenter, randomized, open-label study conducted globally. Participants (n=312) were randomized 1:1 to cinacalcet (n=155) or vitamin D analog (n=157) for 52 weeks. Levels of FGF-23 were measured at baseline and weeks 20 and 52. The absolute and percentage changes from baseline in plasma FGF-23, parathyroid hormone (PTH), calcium (Ca), phosphorus (P), and calcium-phosphorus product (Ca×P) were assessed. Correlations and logistic regression were used to explore relationships between changes in FGF-23 and changes in PTH, Ca, P, and Ca×P from baseline to week 52 by treatment arm. RESULTS: Median (quartiles 1, 3) decrease in FGF-23 concentrations was observed in the cinacalcet arm (-40%; -63%, 16%) compared with median increase in the vitamin D analog arm (47%; 0%, 132%) at week 52 (P<0.001). Changes in FGF-23 in both arms were unrelated to changes in PTH (cinacalcet: r=0.17, P=0.11; vitamin D analog: r=-0.04, P=0.70). Changes in FGF-23 in the vitamin D analog but not the cinacalcet arm were correlated with changes in Ca (cinacalcet: r=0.11, P=0.30; vitamin D analog: r=0.32, P<0.01) and P (cinacalcet: r=0.19, P=0.07; vitamin D analog: r=0.49, P<0.001). Changes in FGF-23 were correlated with changes in Ca×P in both arms (cinacalcet: r=0.26, P=0.01; vitamin D analog: r=0.57, P<0.001). Independent of treatment arm, participants with reductions in P or Ca×P were significantly more likely to show reductions in FGF-23. CONCLUSIONS: During treatment of SHPT, cinacalcet use was associated with a decrease in FGF-23 concentrations, whereas vitamin D analogs were associated with an increase. The divergent effects of these treatments on FGF-23 seem to be independent of modification of PTH. It is possible that effects of cinacalcet and vitamin D analogs on FGF-23 may be mediated indirectly by other effects on bone and mineral metabolism. SN - 1555-905X UR - https://wwww.unboundmedicine.com/medline/citation/25873267/Effect_of_Cinacalcet_and_Vitamin_D_Analogs_on_Fibroblast_Growth_Factor_23_during_the_Treatment_of_Secondary_Hyperparathyroidism_ L2 - https://cjasn.asnjournals.org/cgi/pmidlookup?view=long&amp;pmid=25873267 DB - PRIME DP - Unbound Medicine ER -