Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: results of the IMPACT SHPT study

Ketteler, Markus; Martin, Kévin; Wolf, Myles; Amdahl, Michael; Cozzolino, Mario; Goldsmith, David; Sharma, Amit; Marx, Steven E.; Khan, Samina

doi:10.1093/ndt/gfs018

Cited by 88 publications

(95 citation statements)

References 29 publications

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“…Our results, which show a dissociation between PTH changes and changes in FGF-23, are consistent with recently reported data from the Improved Management of Intact Parathyroid Hormone with Paricalcitol-Centered Therapy Versus Cinacalcet Therapy with Low-Dose Vitamin D in Hemodialysis Patients with SHPT Study (16,25). Cozzolino et al (16) showed that a mean PTH reduction of 56% in the paricalcitol arm was accompanied by an 800%-1500% increase in FGF-23 concentrations, whereas the 38% reduction in PTH observed in the cinacalcet arm was associated with a 25%-32% reduction in FGF-23 concentrations.…”

Section: Discussionsupporting

confidence: 92%

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: Discussionsupporting

confidence: 92%

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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“…Generally, PTX is a valuable option in any patient diagnosed with renal HPT; however, the majority of patients may be controlled medically. Successful medical treatment can be achieved with phosphate binders, calcium supplements, active vitamin D analogues and cinacalcet which alter calcium receptor sensitivity of parathyroid glands and kidneys, thus reducing PTH secretion and restoring calcium-phosphorus homeostasis [17][18][19][20] (evidence level (EL); recommendation grade (RG) EL 1a; RG A) [21]. Cinacalcet is stated to reduce mortality in renal HPT patients, while contradictory reports acclaim a lack of patient-relevant outcomes improvement and relevant side-effects in patients on dialysis [22].…”

Section: Resultsmentioning

confidence: 99%

Surgical management of secondary hyperparathyroidism in chronic kidney disease—a consensus report of the European Society of Endocrine Surgeons

Lorenz

Bartsch

Sancho

et al. 2015

Langenbecks Arch Surg

100

130

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Background Despite advances in the medical management of secondary hyperparathyroidism due to chronic renal failure and dialysis (renal hyperparathyroidism), parathyroid surgery remains an important treatment option in the spectrum of the disease. Patients with severe and complicated renal hyperparathyroidism (HPT), refractory or intolerant to medical therapy and patients with specific requirements in prospect of or excluded from renal transplantation may require parathyroidectomy for renal hyperparathyroidism. Methods Present standard and actual controversial issues regarding surgical treatment of patients with hyperparathyroidism due to chronic renal failure were identified, and pertinent literature was searched and reviewed. Whenever applicable, evaluation of the level of evidence concerning diagnosis and management of renal hyperparathyroidism according to standard criteria and recommendation grading were employed. Results were discussed at the 6th Workshop of the European Society of Endocrine Surgeons entitled Hyperparathyroidism due to multiple gland disease: An evidence-based perspective.Results Presently, literature reveals scant data, especially, no prospective randomized studies to provide sufficient levels of evidence to substantiate recommendations for surgery in renal hyperparathyroidism. Appropriate surgical management of renal hyperparathyroidism involves standard bilateral exploration with bilateral cervical thymectomy and a spectrum of four standardized types of parathyroid resection that reveal comparable outcome results with regard to levels of evidence and recommendation. Specific patient requirements may favour one over the other procedure according to individualized demands. Conclusions Surgery for patients with renal hyperparathyroidism in the era of calcimimetics continues to play an important role in selected patients and achieves efficient control of hyperparathyroidism. The overall success rate and longterm control of renal hyperparathyroidism and optimal handling of postoperative metabolic effects also depend on the timely indication, individually suitable type of parathyroid resection and specialized endocrine surgery.

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“…The mean baseline iPTH in this study was around 500 pg/mL and the primary efficacy end point was the proportion of patients achieving iPTH value of 150-300 pg/mL from week 21 onwards. A greater proportion of patients achieved the primary end point in paricalcitol group compared to cinacalcet group (115,116). However, FGF-23 level was increased significantly with paricalcitol which was likely due to the significant increase in serum phosphate.…”

Section: Selective Vdramentioning

confidence: 85%

Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

Salam

Khwaja

Wilkie

2016

Drugs

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or Article Brief (if supplied by editors): As a 'Therapy in Practice' article, we would like this to provide a succinct, up-to-date clinically orientated guide to the optimum management of secondary hyperparathyroidism in patients with chronic kidney disease. The review should include an appropriate background to the development of SHPT. It should focus primarily on pharmacological treatments but as appropriate, non-pharmacological approaches (dietary, surgical) may be discussed to fully place pharmacological therapy in context. Submission date: 31 st March 2016Word count: 4156 Compliance with Ethical StandardsFunding and conflict of interest statement from each author: Takeaway messages from the article SHPT is associated with adverse outcomes in CKD and dialysis patients  Optimum PTH level is unclear in pre-dialysis CKD and the recommended range is wide for dialysis patients.  Management of SHPT is largely pharmacological focussing on lowering PTH  PTH lowering treatment has not shown improved cardiovascular risk, fractures and mortality. AbstractSecondary hyperparathyroidism (SHPT) is a common complication of CKD and is part of the chronic kidney disease-mineral bone disorder (CKD-MBD). SHPT is associated with increased risk of fracture and mortality, thus SHPT control is recommended as kidney function declines. Effective SHPT management becomes more difficult once skeletal and cardiovascular adverse effects associated with severe SHPT have become established. However, interventional studies to lower parathyroid hormone (PTH) have so far shown inconsistent results in improving patient-centred outcomes such as mortality, cardiovascular events and fracture. Pharmacological treatment effect on PTH level is also inconsistent between predialysis CKD and dialysis patients which adds to the complexity of SHPT management. This review aims to give an overview on the pathophysiology, pharmacological and non-pharmacological treatment for SHPT in CKD including some of the limitations of current therapeutic options.

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Paricalcitol versus cinacalcet plus low-dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: results of the IMPACT SHPT study

Cited by 88 publications

References 29 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

Surgical management of secondary hyperparathyroidism in chronic kidney disease—a consensus report of the European Society of Endocrine Surgeons

Pharmacological Management of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease

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