Use Of Cinacalcet Research Articles

Cinacalcet should be used to treat secondary hyperparathyroidism in stage 3–4 chronic kidney disease

This, the second of two opposing Viewpoints, presents the case for the use of cinacalcet for the treatment of secondary hyperparathyroidism in patients with chronic kidney disease who are not receiving dialysis. The authors assert that cinacalcet effectively reduces serum parathyroid hormone level in this setting, and that any adverse effects of the drug on calcium or phosphorus levels can be managed by monitoring and treating patients accordingly.

Cinacalcet should not be used to treat secondary hyperparathyroidism in stage 3–4 chronic kidney disease

In the first of two opposing Viewpoints, Daniel W Coyne questions the use of cinacalcet to treat secondary hyperparathyroidism in non-dialysis-dependent patients with chronic kidney disease. He highlights the absence of FDA approval and the lack of published data for cinacalcet in this setting. Cinacalcet does not, he argues, address a universal pathophysiologic feature of secondary hyperparathyroidism; in addition, it has considerable adverse effects.

Use of cinacalcet (Mimpara ®/Sensipar ®) in daily clinical practice

Use of cinacalcet (Mimpara ®/Sensipar ®) in daily clinical practice

Use of Cinacalcet during Pregnancy in Hypophosphatemic Vitamin D Resistant Rickets with Tertiary Hyperparathyroidism

Use of Cinacalcet during Pregnancy in Hypophosphatemic Vitamin D Resistant Rickets with Tertiary Hyperparathyroidism

Potential future uses of calcimimetics in patients with chronic kidney disease.

Cinacalcet has proven effective in the treatment of secondary hyperparathyroidism (SHPT) in dialysis patients, and it may also have benefits in stage 3 and 4 chronic kidney disease (CKD). The efficacy of cinacalcet in the treatment of SHPT was investigated in a study of 54 patients with stage 3 and 4 CKD not receiving dialysis. A significant number of these patients achieved at least a 30% reduction in parathyroid hormone (PTH) from baseline with cinacalcet therapy compared with placebo (56% versus 19%; P = 0.006). Another potential use of cinacalcet is in the treatment of persistent hyperparathyroidism (HPT) after kidney transplantation. The pathophysiologic considerations for persistent HPT in patients who have undergone renal transplantation are different from those in stage 3 and 4 CKD. Post-transplant patients with normal graft function often present with hypercalcaemia, low serum phosphorus and persistently elevated levels of PTH. In eight small open-label studies including a total of 83 patients with persistent HPT after successful kidney transplantation, cinacalcet treatment effectively corrected hypercalcaemia and significantly reduced elevated PTH levels. These studies suggest that cinacalcet therapy is an effective therapy in controlling hyperparathyroidism in patients with stage 3 and 4 CKD and in post-transplant patients with persistent hyperparathyroidism.

Hypercalciuria induced by a high dose of cinacalcet in a renal-transplant recipient

The successful use of cinacalcet in dialysis patients and in patients with primary hyperparathyroidism has prompted transplant physicians to use it to treat renal-transplant patients with persisting hyperparathyroidism. However, in the setting of kidney transplantation, many questions remain unanswered, i.e. the time of initiation of cinacalcet after transplantation, its dosage and the side effects on kidney function all remain unknown. Herein, we report on a kidney-transplant recipient with persisting hyperparathyroidism who developed hypercalciuria afterreceiving high doses of cinacalcet. Cinacalcet was started 3 months after transplantation at a once-daily dose of 60 mg. Thereafter, the dosage was increased progressively because of persistant hyperparathyroidism and hypercalcemia. At a dose of 90 mg b.i.d, hypercalciuria occurred. The latter disappeared after reduction of cinacalcet dosage. Cinacalcet might be responsible for urinary calcium excretion, either by reduction of tubular calcium reabsorption via the reduction of PTH level, or by its direct effect on the calcium sensor receptor located in the upper thick ascending limb of the loop of Henle. We conclude that cinacalcet should be used with caution in renal-transplant patients. Further investigations are required to determine the best way to use this drug in this setting.

Parathyroidectomy Versus Cinacalcet Hydrochloride–Based Medical Therapy in the Management of Hyperparathyroidism in ESRD: A Cost Utility Analysis

Previously, patients with end-stage renal disease (ESRD) with uncontrolled hyperparathyroidism had few options other than parathyroidectomy, which was reserved for patients refractory to medical therapy. Newer calcimimetic agents, such as cinacalcet, may be an alternative, but raise the possibility of indefinite medical treatment that also would increase costs. Cost utility analysis. Base case consisted of prevalent adult US patients with ESRD refractory to management with standard medical therapy. Characteristics were obtained from patients who underwent parathyroidectomy in 2001, and, for purposes of comparison, patients in whom cinacalcet was used were assigned similar characteristics. All data came from preexisting literature and trials or from US Renal Data System analysis files. Use of cinacalcet hydrochloride versus parathyroidectomy. Medicare and societal costs and quality-adjusted life-years from the date of parathyroidectomy or use of cinacalcet followed up for 2 years, respectively. Primary outcomes were cost (measured in US dollars) and cost utility measured using cost per quality-adjusted life-years. At base-case surgical and drug costs, surgical and drug success rates, complication rates/costs, and benefit from correction of hyperparathyroidism, parathyroidectomy was found to be both less expensive and more cost-effective at 7.25 +/- 0.25 months. Parathyroidectomy became more cost-effective at 15.28 to 16.32 months at the upper limit of sensitivity analysis, when drug/surgical costs and success/complication rates/costs were maximally weighted to favor cinacalcet-based medical therapy. We assumed current costs of both cinacalcet and parathyroidectomy and assumed cinacalcet use would be indefinite. For patients with ESRD with uncontrolled hyperparathyroidism who are good candidates for either drug therapy or surgery, cinacalcet hydrochloride is the most cost-effective modality if the patient is to remain on dialysis therapy for 7.25 +/- 0.25 months. Cinacalcet may be more optimal if used in patients who have high risk of mortality or who would expect to receive a kidney transplant quickly. For other subgroups, parathyroidectomy dominated.

39: Assessing the Use of the Calcimimetic Cinacalcet with Low Dose Vitamin D Versus Escalating Doses of Vitamin D Alone in the Treatment of Secondary Hyperparathyroidism (HPT)—The Achieve Study

39: Assessing the Use of the Calcimimetic Cinacalcet with Low Dose Vitamin D Versus Escalating Doses of Vitamin D Alone in the Treatment of Secondary Hyperparathyroidism (HPT)—The Achieve Study

Preliminary Experience With Cinacalcet Use in Persistent Secondary Hyperparathyroidism After Kidney Transplantation

There is limited experience with the use of cinacalcet in the treatment of persistent secondary hyperparathyroidism after kidney transplantation. We retrospectively analyzed our experience in 18 renal allograft recipients who initiated cinacalcet therapy from 1 month to 23 years (median 3 years) posttransplantation and were maintained on the drug for 6 months. The daily dose was titrated from 30 mg up to a maximum of 180 mg to achieve a reduction in serum intact parathyroid hormone (PTH) levels. Sustainable, significant decreases in mean calcium and alkaline phosphatase were noted at 1 month and intact PTH by 3 months, with 50% of patients achieving at least a 30% drop in PTH levels at 6 months. Serum phosphorous increased at 6 months, whereas urine N-telopeptides decreased. There were no significant changes in serum osteocalcin, albumin, and hemoglobin levels. We did not observe a tachyphylaxis phenomenon. Two patients reported occasional nausea, but did not require medication discontinuation. Estimated glomerular filtration rate did decrease progressively over the 6-month period. Cinacalcet appears to be an effective drug for the treatment of posttransplant hypercalcemia due to persistent secondary hyperparathyroidism. Further studies with more patients and longer follow-up will be needed to better elucidate the efficacy/safety profile for this agent, particularly with regard to long-term bone histology and renal outcomes.

The UK NICE has issued guidance to the NHS in England and Wales on the use of cinacalcet for the treatment of secondary hyperparathyroidism.

The UK NICE has issued guidance to the NHS in England and Wales on the use of cinacalcet for the treatment of secondary hyperparathyroidism.

The UK NICE has issued guidance to the NHS in England and Wales on the use of cinacalcet for the treatment of secondary hyperparathyroidism.

The UK NICE has issued guidance to the NHS in England and Wales on the use of cinacalcet for the treatment of secondary hyperparathyroidism.

Use of cinacalcet in a patient on long-term dialysis with end-stage renal failure and refractory secondary hyperparathyroidism

Progressive secondary hyperparathyroidism (sHPT) is a serious complication of chronic renal failure (CRF) caused by cellular transformation of parathyroid glands leading to aggressive growth potential and diminished expression of both the vitamin D receptor and calcium-sensing receptor (CaSR) [1]. These changes precipitate increased secretion of parathyroid hormone (PTH) (>400 pg/ml) and disruptions in the homeostatic control of serum calcium, serum phosphate and vitamin D [2,3]. While many patients with sHPT can be managed by conventional pharmacological therapy (oral phosphate binders, oral or intravenous calcitriol) and/or dietary restrictions or supplementation, these treatments fail to control disease progression in some patients. Pharmacological treatments for sHPT may also be associated with severe side effects [3], leading to vascular and soft tissue calcification [4]. Parathyroidectomy is a successful treatment for advanced autonomous sHPT that is unresponsive to medical treatment. However, sHPT may persist and progress if residual parathyroid gland tissue remains or if supernumerary glands are overlooked [5]. In addition, approximately 20% of patients who undergo autograft after parathyroidectomy develop graft-dependent recurrent hyperparathyroidism [6]. Regardless of cause, treatment-refractory patients with persistent sHPT are at risk of serious clinical complications including muscle weakness, osteodystrophy and soft tissue and vascular calcification [2]. Vascular calcification [7] and PTH levels >476 pg/ml [8] have been independently associated with an increased risk of a fatal cardiovascular event. Clinical management of dialysis patients with sHPT is particularly challenging and effective treatments are needed. Cinacalcet, a new calcimimetic agent that targets the CaSR on parathyroid cells and increases its sensitivity to calcium [9], may fill this therapeutic gap. Cinacalcet has recently been approved for the treatment of sHPT in patients with chronic kidney disease on dialysis.

Evaluation and management of bone disease following renal transplantation

Purpose of review Bone disease is a common problem after renal transplantation. Interventions to alleviate bone disease such as bisphosphonates and vitamin D analogues are widely available and are increasingly used in the transplant population. This article reviews the literature published within the past 12 months regarding the assessment and treatment of bone disease in renal transplant recipients. Recent findings Recent literature details new diagnostic approaches to identifying patients with bone fragility including quantitative ultrasound and computed tomography. Recent randomized, controlled trials examine the use of vitamin D and analogues (n = 2) and alendronate (n = 1) to prevent bone disease in renal transplantation. Two observational studies of the use of cinacalcet to treat posttransplant hyperparathyroidism have become available and randomized trials are awaited. Summary There continues to be a paucity of evidence that intervention for bone disease in the renal transplant population achieves a reduction in fracture events, and treatment remains associated with cost and toxicity. The diagnostic utility of radiology and bone histomorphometry to identify patients most at risk of transplant-related fracture also remains imprecise.