Rapid decrease of intact parathyroid hormone could be a predictor of better response to cinacalcet in hemodialysis patients

Abstract

Purpose: Cinacalcet is effective for treating refractory secondary hyperparathyroidism (SHPT), but little is known about the response rates and clinical factors influencing the response.

Materials and methods: A prospective, single-arm, multi-center study was performed for 24 weeks. Cinacalcet was administered to patients with intact parathyroid hormone (iPTH) level greater than 300 pg/mL. Cinacalcet was started at a dose of 25 mg daily and titrated until 100 mg to achieve a serum iPTH level<300 pg/mL (primary end point). Early response to cinacalcet was defined as a decrease of iPTH more than 50% within one month.

Results: Fifty-seven patients were examined. Based on the magnitude of iPTH decrease, patients were divided into responder (n=47, 82.5%) and non-responder (n=10, 17.5%) groups. Among the responders, 38 achieved the primary end point, whereas 9 patients showed a reduction in serum iPTH of 30% or more, but did not reach the primary end point. Compared to non-responders, responders were significantly older (p=0.026), female (p=0.041), and diabetics (p<0.001). Additionally, early response was observed more frequently in the responders (30/47, 63.8%), of whom the majority (27/30, 90.0%) achieved the primary end point. Multivariate analysis showed that lower baseline iPTH levels [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.99], the presence of diabetes (OR 46.45, CI 1.92-1125.6) and early response (OR 21.54, CI 2.94-157.7) were significant clinical factors affecting achievement of iPTH target.

Conclusion: Cinacalcet was effective in most hemodialysis patients with refractory SHPT. The presence of an early response was closely associated with the achievement of target levels of iPTH.

Fig. 1

Flow diagram of patient recruitment and progress.

Fig. 2

Parathyroid gland size and serum iPTH levels. Maximal size of parathyroid gland detected on neck CT was highly correlated with serum iPTH levels (r=0.521, p<0.001). iPTH, intact parathyroid hormone.

Fig. 3

Effects of cinacalcet treatment on serum iPTH levels. In patients who achieved primary or secondary end point (responders), iPTH levels decreased significantly from baseline, whereas the levels were not changed or mildly increased in the non-responder group. iPTH, intact parathyroid hormone.

Fig. 4

The cumulative proportion of patients to reach primary or secondary end point per month.

Fig. 5

Changes in serum calcium, phosphorus and calcium phosphorus products levels with cinacalcet treatment. Serum calcium levels were reduced in all three groups (p<0.001), however, the changes of serum phosphorus and calcium phosphorus products levels were statistically insignificant. Data were analyzed by repeated measures ANOVA. ANOVA, analysis of variance.

Fig. 6

The response rates according to baseline iPTH level. iPTH, intact parathyroid hormone.

Fig. 7

Response rate to cinacalcet according to diabetes. Diabetic patients showed a more favorable response to cinacalcet compared to non-diabetics (p<0.001).

Supplemental Fig. 1

Median iPTH levels and response rate to cinacalcet according to age group. iPTH, intact parathyroid hormone.

Supplemental Fig. 2

Clinical factors affecting achievement of iPTH target. iPTH, intact parathyroid hormone; DM, diabetes mellitus.