Achieving NKF-K/DOQI™ bone metabolism and disease treatment goals with cinacalcet HCl

Moe, Sharon M.; Chertow, Glenn M.; Coburn, Jack W.; Quarles, L. Darryl; Goodman, William G.; Block, Geoffrey A.; Drüeke, Tilman B.; Cunningham, John A.; Sherrard, Donald J.; McCary, Laura C.; Olson, Kurt; Turner, Stewart A.; Martin, Kévin

doi:10.1111/j.1523-1755.2005.67139.x

Cited by 305 publications

(265 citation statements)

References 30 publications

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“…Both groups exhibited similar reductions in actual and percent changes in 6-mo intervals for PTH, CaϫP, Ca, and P levels following cinacalcet treatment. The efficacy data of the current study is consistent with analysis of pooled data from the four double-blind, placebocontrolled lead-in studies of cinacalcet in patients with SHPT and stage 5 CKD on dialysis and traditional therapies (vitamin D sterols and oral phosphate binder), showing cinacalcet to be significantly more effective than placebo at maintaining recommended levels of PTH, CaϫP, Ca, and P (19). Treatment-related AEs reported in the double-blind placebo-controlled studies among subjects randomized to cinacalcet were limited to nausea and vomiting, which were generally mild to moderate in severity and transient in duration.…”

Section: Discussionsupporting

confidence: 68%

Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

Sprague

Evenepoel²,

Curzi³

et al. 2009

Clinical Journal of the American Society of Nephrology

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Background & objectives: Chronic kidney disease (CKD) is commonly complicated by secondary hyperparathyroidism (SHPT), leading to increased risk of morbidity and mortality. SHPT is a progressive disease often requiring long-term therapy to control parathyroid hormone (PTH) and mineral imbalances. Vitamin D sterols and phosphate binders, used as traditional therapies to lower PTH and phosphorus, may provide inadequate long-term control for many dialysis patients. Cinacalcet, by simultaneously lowering PTH, calcium, phosphorus, and calcium-phosphorus levels, may maintain PTH and mineral balance in these individuals. However, as with traditional therapies, long-term data are limited.Design, setting, participants, & measurement: Dialysis subjects from at least one of five lead-in studies (double-blind placebo-controlled, including one extension trial) completing up to 52 wk of either cinacalcet or placebo were eligible for this open-label extension study, including an 8-wk dose titration (initiated at 30 mg/d), followed by 24-wk maintenance and up to 132 wk of follow-up. Final efficacy analysis was at week 180.Results: Three hundred thirty-four of 589 enrolled subjects received cinacalcet from the beginning of the lead-in study. Weekly median PTH values were <300 pg/ml (weeks 16 through 180) and median Ca؋P values were <55 mg 2 /dl 2 (weeks 4 through 180). Similar results were exhibited in the 255 subjects who initially received placebo. Among the patients exposed to cinacalcet from the beginning of the lead-in study, 3% of subjects exhibited treatment-related serious adverse events.Conclusions: Cinacalcet effectively maintained PTH, Ca and P reductions in dialysis subjects for up to 180 wk. Clin J Am Soc Nephrol 4: 1465-1476, 2009. doi: 10.2215 S econdary hyperparathyroidism (SHPT) occurs often in chronic kidney disease (CKD). It is characterized by increases in the synthesis and secretion of parathyroid hormone (PTH) and by disturbances in calcium (Ca), phosphorus (P), and vitamin D metabolism (1). SHPT is a progressive disorder among those undergoing dialysis in whom PTH levels increase by an average of 6% per year (2). Elevated PTH, Ca, P, and CaϫP levels and alterations in vitamin D metabolism are associated with important adverse outcomes, including cardiovascular disease, in such patients (3-6).The long-term efficacy and safety of traditional therapies for SHPT have not been critically examined. Despite many years of clinical use, results from prospective clinical trials describing therapeutic responses to any vitamin D sterol among dialysis patients with SHPT lasting more than 13 mo are available from only six patients after 2 yr of follow-up (20). Sustained treatment with vitamin D alone often proves inadequate for dialysis patients with SHPT (7-9). Disturbances in calcium and phosphorus metabolism frequently disrupt therapy (10), rendering consistent biochemical control of the disorder difficult (8).Treatment with cinacalcet hydrochloride (cinacalcet) often concurrently lowers PTH, Ca, P, and CaϫP levels a...

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Section: Discussionsupporting

confidence: 68%

Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

Sprague

Evenepoel²,

Curzi³

et al. 2009

Clinical Journal of the American Society of Nephrology

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“…In addition, it supports studies that have shown that cinacalcet has no clinically relevant interaction with standard immunosuppressive drugs (53). The most frequently reported treatmentemergent AE in the cinacalcet group was diarrhea, similar to what has been reported in other CKD cohorts (7,9,21,54). Previously, concerns have been raised about decreases in renal function following cinacalcet therapy for the treatment of persistent HPT including limited, but significant drops in eGFR (29).…”

Section: Evenepoel Et Alsupporting

confidence: 71%

“…These morphological transformations are associated with down-regulation of the vitamin D receptor and calcium-sensing receptor (CaSR), which result in parathyroid gland resistance to inhibitory feedback mechanisms (6). Successful renal transplantation corrects the physiologic and metabolic abnormalities responsible for the pathogenesis of secondary HPT (7)(8)(9). However, while endorgan resistance to the action of PTH rapidly wanes parallel to the recovery of renal function, regression of parathyroid gland hyperplasia is uncommon.…”

Section: Introductionmentioning

confidence: 99%

A Randomized Study Evaluating Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients With Persistent Hyperparathyroidism

Evenepoel

Cooper

Holdaas

et al. 2014

American Journal of Transplantation

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Persistent hyperparathyroidism (HPT) after kidney transplantation (KTx) is associated with hypercalcemia, hypophosphatemia and abnormally high levels of parathyroid hormone (PTH). In this randomized trial, cinacalcet was compared to placebo for the treatment of hypercalcemia in adult patients with persistent HPT after KTx. Subjects were randomized 1:1 to cinacalcet or placebo with randomization stratified by baseline corrected total serum calcium levels ( 11.2 mg/dL [2.80 mmol/L] or >11.2 mg/dL [2.80 mmol/L]). The primary end point was achievement of a mean corrected total serum calcium value <10.2 mg/dL (2.55 mmol/L) during the efficacy period. The two key secondary end points were percent change in bone mineral density (BMD) at the femoral neck and absolute change in phosphorus; 78.9% cinacalcetversus 3.5% placebo-treated subjects achieved the primary end point with a difference of 75.4% (95% confidence interval [CI]: 63.8, 87.1), p < 0.001. There was no statistical difference in the percent change in BMD at the femoral neck between cinacalcet and placebo groups, p ¼ 0.266. The difference in the change in phosphorus between the two arms was 0.45 mg/dL (95% CI: 0.26, 0.64), p < 0.001 (nominal). No new safety signals were detected. In conclusion, hypercalcemia and hypophosphatemia were effectively corrected after treatment with cinacalcet in patients with persistent HPT after KTx.

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“…Initial randomized controlled studies (RCT) with placebo arm recognized that cinacalcet could cause severe hypocalcaemia (<7.5 mg/dl) in up to 5 % of patients requiring oral calcium and/or vitamin D substitution [17]. Even more patients (35-45 %) experience digestive intolerance, in 8-15 %, requiring to terminate treatment [19,20,23] (EL 2b; RG B). The benefit of cinacalcet to improve bone mineral density is described; however, data are scarce and further studies with long-term follow-up are needed to substantiate this effect [24] (EL 3a).…”

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

108

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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Achieving NKF-K/DOQI™ bone metabolism and disease treatment goals with cinacalcet HCl

Abstract: In subjects on dialysis with secondary HPT, cinacalcet facilitates achievement of the K/DOQI-recommended targets for PTH, calcium, phosphorus, and Ca x P.

Cited by 305 publications

References 30 publications

Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

A Randomized Study Evaluating Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients With Persistent Hyperparathyroidism

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

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