Changes in fibroblast growth factor 23 during treatment of secondary hyperparathyroidism with alfacalcidol or paricalcitol

Hansen, Ditte; Rasmussen, Knud; Pedersen, Susanne Møller; Rasmussen, Lars Melholt; Brandi, Lisbet

doi:10.1093/ndt/gfr668

Cited by 55 publications

(40 citation statements)

References 32 publications

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“…This would indicate that the differential effects of cinacalcet and vitamin D analogs on FGF-23 are not likely mediated by their effects on PTH but rather, may be mediated by direct effects on bone cells and/or other indirect effects on mineral metabolism, such as changes in Ca and/or P concentrations. Although previous studies have also noted these opposite effects of vitamin D analogs and cinacalcet on FGF-23 concentrations (16)(17)(18)(19)(20)(21)(22), this trial is unique in that participants were randomized to treatment with either cinacalcet or vitamin D analogs as monotherapy, thereby permitting a direct comparison of their effects. Both animal and human studies have shown that PTH administration increases FGF-23 (6-10), supporting the hypothesis that PTH is an important regulator of FGF-23.…”

Section: Discussionmentioning

confidence: 99%

“…Studies have shown that treatment of SHPT with vitamin D analogs is associated with increases in FGF-23 concentrations, whereas use of cinacalcet is associated with a reduction in FGF-23 (16)(17)(18)(19)(20)(21)(22). However, the majority of these trials were single-arm studies, and in those that used cinacalcet, it was added to standard-of-care treatment regimens that generally included vitamin D analogs.…”

Section: Introductionmentioning

confidence: 99%

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Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism

Sprague

Wetmore

Gurevich³

et al. 2015

Clinical Journal of the American Society of Nephrology

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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 (Ca3P) were assessed. Correlations and logistic regression were used to explore relationships between changes in FGF-23 and changes in PTH, Ca, P, and Ca3P from baseline to week 52 by treatment arm.Results Median (quartiles 1, 3) decrease in FGF-23 concentrations was observed in the cinacalcet arm (240%; 263%, 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=20.04, 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 Ca3P 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 Ca3P 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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism

Sprague

Wetmore

Gurevich³

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…FGF23 levels are increased as kidney function declines [47] and in dialysis patients treatment with vitamin D analogs increases FGF23 [20]. High FGF23 levels are associated with increased mortality and left ventricular hypertrophy in dialysis patients [48,49].…”

Section: Discussionmentioning

confidence: 99%

The influence of vitamin D analogs on calcification modulators, N-terminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients: a randomized crossover study

Hansen

Rasmussen

et al. 2014

BMC Nephrol

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BackgroundThe risk of cardiovascular disease is tremendously high in dialysis patients. Dialysis patients treated with vitamin D analogs show decreased cardiovascular morbidity and mortality compared with untreated patients. We examined the influence of two common vitamin D analogs, alfacalcidol and paricalcitol, on important cardiovascular biomarkers in hemodialysis patients. Anti-inflammatory effects and the influence on regulators of vascular calcification as well as markers of heart failure were examined.MethodsIn 57 chronic hemodialysis patients enrolled in a randomized crossover trial comparing paricalcitol and alfacalcidol, we examined the changes in osteoprotegerin, fetuin-A, NT-proBNP, hs-Crp, IL-6 and TNF-α, during 16 weeks of treatment.ResultsNT-proBNP and osteoprotegerin increased comparably in the paricalcitol and alfacalcidol-treated groups. Fetuin-A increased significantly in the alfacalcidol-treated group compared with the paricalcitol-treated group (difference 32.84 μmol/l (95% C.I.; range 0.21–67.47)) during the first treatment period. No difference was found between the groups during the second treatment period, and IL-6, TNF-α and hs-Crp were unchanged in both treatment groups.ConclusionsParicalcitol and alfacalcidol modulate regulators of vascular calcification. Alfacalcidol may increase the level of the calcification inhibitor fetuin-A. We did not find any anti-inflammatory effect or difference in changes of NT-proBNP.Trial registryClinicalTrials.gov NCT00469599 May 3 2007.

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“…Further, VDRA administration in dialysis patients was shown to increase FGF23 concentrations [43], an established independent predictor of mortality in this population [44]. …”

Section: Another Paradigm Shift In Vdra Use For Shptmentioning

confidence: 99%

Active Vitamin D in Chronic Kidney Disease: Getting Right Back Where We Started from?

Negrea

2018

Kidney Dis

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Background: The vitamin D system is essential for optimal health in humans. Circulating calcitriol, a key metabolite in maintaining calcium and phosphorus homeostasis, is produced in the kidney. In kidney failure, calcitriol levels progressively decrease, contributing to the development of renal secondary hyperparathyroidism (SHPT). Summary: For years, SHPT had a central role in the disturbed mineral metabolism of renal patients. As calcitriol deficiency contributes to SHPT development, treatment with calcitriol or other compounds able to activate the vitamin D receptor (VDR) was one of the mainstays of therapy for renal patients in the last 40 years. In this review, we discuss how the treatment with VDR activators (VDRA) evolved during this time in the United States, as well as the main factors responsible for these changes. Key Messages: Management of SHPT with VDRA in renal patients has undergone a few paradigm shifts over the last 40 years. When treating SHPT, the newly developed therapies as well as VDRA need to be carefully considered and used appropriately. Nephrologists need to use an integrated approach that avoids excessive use of VDRA, ensures replenishment of vitamin D stores, and avoids hypercalcemia and hyperphosphatemia.

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Changes in fibroblast growth factor 23 during treatment of secondary hyperparathyroidism with alfacalcidol or paricalcitol

Abstract: Alfacalcidol and paricalcitol increase the plasma levels of FGF23 equally and substantially in haemodialysis patients.

Cited by 55 publications

References 32 publications

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism

Effect of Cinacalcet and Vitamin D Analogs on Fibroblast Growth Factor-23 during the Treatment of Secondary Hyperparathyroidism

The influence of vitamin D analogs on calcification modulators, N-terminal pro-B-type natriuretic peptide and inflammatory markers in hemodialysis patients: a randomized crossover study

Active Vitamin D in Chronic Kidney Disease: Getting Right Back Where We Started from?

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