This article appraisal is part of the EMiNEM Bone and Mineral Metabolism Series. Click here to reach the EMiNEM homepage on UKidney
To determine whether cinacalcet is capable of inducing a reduction in parathyroid volume in addition to PTH level.
Study Design and Study Population
81 stable chronic hemodialysis patients with moderate to severe secondary hyperparathyroidism (intact PTH > 300 pg/ml) on standard therapy for CKD-MBD (oral phosphate binders plus vitamin D analogues). Size of parathyroid volume determined by ultrasonography. 56 patients had parathyroid glands smaller than 500 mm3 (group S) and 25 patients had at least one enlarged gland larger than 500 mm3 (group L).
Intervention or Observation
Cinacalcet was given in a dose sufficient to achieve an intact PTH < 180 pg/ml. Ultrasonography was performed at baseline, week 26 and week 52. The study group was compared to historical controls.
Primary and Secondary End-Points
Primary: Proportion of patients with a mean intact PTH level < 180 pg/ml in last 14 weeks (of 52) of cinacalcet treatment.
Secondary: Proportion of patients with a > 30% reduction from baseline in intact PTH.
The change in parathyroid gland volume as evaluated by ultrasonography.
Statistical analysis: Differences in parathyroid gland volume at baseline and at week 25 and week 52 were analyzed on the basis of the as-treated analysis, using repeated measures ANOVA followed by the Bonferroni post-hoc test.
Treatment with cinacalcet (dose between 25-100 mg) effectively decreased intact PTH by 55% from baseline in group S and by 58% in group L. Cinacalcet therapy also resulted in a significant reduction in parathyroid gland volume regardless of pretreatment size which was in sharp contrast to historical controls where parathyroid gland volume progressively increased with traditional therapy alone.
This prospective multicenter study was carried out in stable hemodialysis patients for a 52-week period which is longer than many similar studies. The study group was divided into 2 subgroups based on the size of the parathyroid glands but the findings were similar in both groups with a significant reduction in PTH levels and parathyroid gland size. High resolution sonography was carried out with a standardized protocol.
The major limitation in this study was the use of historical controls.
This study confirms the effectiveness of cinacalcet in the suppression of secondary hyperparathyroidism. In contrast to vitamin D analogues, there is no predisposition to hypercalcemia or hyperphosphatemia. This is one of the first reports to document a significant decrease in parathyroid gland volume with the administration of cinacalcet which occurred in both moderate and severe secondary hyperparathyroidism. Unanswered questions are whether patients can eventually discontinue cinacalcet and whether this therapy decreases the incidence of parathyroidectomy.
Reviewed by Reviewed by Dr. Paul Barre