Cinacalcet Hydrochloride Therapy for Secondary Hyperparathyroidism in Hemodialysis Patients

Abstract

This study compared the efficacy of a cinacalcet-based regimen with unrestricted conventional therapy (vitamin D and phosphate binders) for achieving Kidney Disease Outcome Quality Initiative (K/DOQI) targets for dialysis patients. In this multicenter, prospective study, hemodialysis patients with poorly controlled secondary hyperparathyroidism (SHPT) were randomized to receive a cinacalcet-based regimen (n=55) or a conventional therapy (n=27). Doses of cinacalcet, vitamin D sterols, and phosphate binders were adjusted during a 12-week dose-titration phase to achieve intact parathyroid hormone (iPTH) levels ≤ 31.8 pmol/L. The primary end point was the percentage of patients with values in this range during a 24-week efficacy-assessment phase. The clinical response to 36-week cinacalcet treatment was evaluated. A dual energy X-ray absorptiometry was performed before and after 36 weeks of cinacalcet therapy. Fifty-eight percent of the cinacalcet group reached the primary end point, as compared with 19% of the conventional therapy group (P=0.001). A higher percentage of patients receiving the cinacalcet-based regimen versus conventional therapy achieved the targets for calcium, phosphorus and Ca×P. Achievement of targets was greatest in patients with less severe disease (intact PTH range, 31.8 to 53 pmol/L). Cinacalcet therapy increased proximal femur bone mineral density (BMD), but did not affect the lumbar spine. Itching intensity decreased significantly. Cinacalcet based treatment facilitates achievement of the K/DOQI targets for iPTH and bone mineral metabolism compared with conventional therapy in hemodialysis patients. Suppression of iPTH with cinacalcet reverses bone loss in the proximal femur. Cinacalcet alleviated itching.

Rates and Outcomes of Parathyroidectomy for Secondary Hyperparathyroidism in the United States

“…Although the use of calcitriol, active vitamin D analogs, and cinacalcet has been shown to reduce PTH and although cinacalcet reduced rates of parathyroidectomy in some clinical studies (9)(10)(11), little is known regarding effects of medical management on parathyroidectomy rates in clinical practice. Some reports showed that the laboratory changes observed in clinical practice were less dramatic than those in clinical trials (7), and parathyroidectomy rates decreased through 2004 and 2005 but increased again in 2006 (6).…”

Cinacalcet for Treatment of Chronic Kidney Disease-Mineral and Bone Disorder: A Meta-Analysis of Randomized Controlled Trials

“…There were 15 trials comparing cinacalcet to placebo [8, 19-28, 30, 31, 33, 39], 3 trials comparing cinacalcet to standard treatment (i.e., a phosphate binder and/or vitamin D compound) [9, 10, 38], and 6 trials comparing cinacalcet and a vitamin D compound to a vitamin D compound alone [29, 32, 34-37]. Twenty-one trials involved hemodialysis patients [8, 10, 19-24, 26-33, 35-39], 1 trial involved peritoneal dialysis patients [34], and 2 trials enrolled patients on a combination of hemodialysis and peritoneal dialysis [9, 25]. The mean age ranged from 46 to 65 years, and duration of treatment spanned from 7 days to 12 months.…”

“…Fifty-six articles were retrieved for detailed evaluation, of which 24 RCTs with 10,031 participants fulfilled eligibility criteria, and were included in the meta-analysis (Fig. 1) [8-10, 19-39]. …”

“…Five studies were conducted in Asia [10, 27, 30, 34, 39], 1 study in Europe [9], 6 studies in America [19, 20, 22, 24, 29, 38], and 12 in multiple countries [8, 21, 23, 25, 26, 28, 31-33, 35-37]. There were 15 trials comparing cinacalcet to placebo [8, 19-28, 30, 31, 33, 39], 3 trials comparing cinacalcet to standard treatment (i.e., a phosphate binder and/or vitamin D compound) [9, 10, 38], and 6 trials comparing cinacalcet and a vitamin D compound to a vitamin D compound alone [29, 32, 34-37]. Twenty-one trials involved hemodialysis patients [8, 10, 19-24, 26-33, 35-39], 1 trial involved peritoneal dialysis patients [34], and 2 trials enrolled patients on a combination of hemodialysis and peritoneal dialysis [9, 25].…”

“…­FGF-23 has direct effects on cardiac myocyte [4] and is associated with left ventricular hypertrophy and has been linked to an increased risk for cardiovascular mortality [4-6]. Approved in the United States in 2004 [7], cinacalcet is a calcimimetic agent that acts by activating the calcium-sensing receptor in the parathyroid gland to lower serum PTH, and is used to treat secondary hyperparathyroidism [8-10]. …”