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

Abstract

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.