Cinacalcet HCl and Concurrent Low-dose Vitamin D Improves Treatment of Secondary Hyperparathyroidism in Dialysis Patients Compared with Vitamin D Alone

Abstract

Background and objectives: Patients with chronic kidney disease (CKD) receiving dialysis often develop secondary hyperparathyroidism with disturbed calcium and phosphorus metabolism. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) was established to guide treatment practices for these disorders. The ACHIEVE study was designed to test two treatment strategies for achieving KDOQI goals.Design, setting, participants, measurements: Individuals on hemodialysis treated with vitamin D sterols were enrolled in this 33-week study. Subjects were randomly assigned to treatment with either cinacalcet and low-dose vitamin D (Cinacalcet-D) or flexible vitamin D alone (Flex-D) to achieve KDOQI-recommended bone mineral targets. ACHIEVE included a 6-week screening phase, including vitamin D washout, a 16-week dose-titration phase, and an 11-week assessment phase.Results: Of 173 subjects enrolled, 83% of Cinacalcet-D and 67% of Flex-D subjects completed the study. A greater proportion of Cinacalcet-D versus Flex-D subjects had a >30% reduction in parathyroid hormone (PTH) (68% versus 36%, P < 0.001) as well as PTH <300 pg/ml (44% versus 23%, P ‫؍‬ 0.006). The proportion of subjects simultaneously achieving targets for intact PTH (150 -300 pg/ml) and calcium-phosphorus product (Ca؋P) (<55 mg 2 /dl 2 ) was also greater (21% versus 14%), but this was not statistically significant. This was attributable to 19% of Cinacalcet-D subjects with a PTH value below the KDOQI target range.Conclusions: Achievement of KDOQI targets was difficult, especially with Flex-D. Maintaining calcium and phosphorus target values precluded the use of vitamin D doses necessary to lower PTH to within the narrow target range and highlighted limitations inherent to the KDOQI treatment algorithm.

Prescription Patterns and Mineral Metabolism Abnormalities in the Cinacalcet Era

“…Several studies have reported the effect of cinacalcet on decreasing iPTH levels (1,4,5), with associations between cinacalcet administration and decreased iPTH levels in this study found to be consistent with those in randomized control studies (4,5) and a previous observational study (1). However, little is known about the effect of concomitant therapy with cinacalcet and VDRA (15), particularly with regard to the effect of VDRA dosage change in concomitant therapy.…”

“…Although a number of previous studies have reported that cinacalcet administration reduced levels of phosphorus and calcium (1,4,5,(7)(8)(9), few have examined the effects of concomitant therapy with VDRA. We found that a combination pattern involving starting cinacalcet and decreased VDRA was effective in achieving target levels of phosphorus and calcium.…”

Effects of Cinacalcet and Concurrent Low-Dose Vitamin D on FGF23 Levels in ESRD

“…To assess the effects of treatment with Cinacalcet and calcitriol analogs on circulating FGF23 levels in ESRD patients, we measured FGF23 levels in participants of the ACHIEVE study, a randomized controlled clinical trial of HD patients with SHPT designed to test whether treatment with Cinacalcet plus lowdose calcitriol analogs (Cinacalcet-D) would compare with treatment with calcitriol analogs alone in (Flex-D) in attainment of National Kidney Foundation K/DOQI mineral metabolic parameters (25). In this secondary analysis, we used prospectively collected samples from a subset of participants to study change in FGF23 levels in response to the two treatment strategies.…”

Calcimimetics in CKD—results from recent clinical studies

“…Cunningham et al [14] Meta-analysis of eight randomized, vitamin D alone (where flexible dosing was allowed) in 173 dialysis patients (ACHIEVE) [12]. In this study, the fixed combination of cinacalcet plus low-dose vitamin D resulted in an effective PTH lowering when compared to vitamin D alone.…”