Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study

Hyo Jin Kim, Hyunsuk Kim, Nara Shin, Ki Young Na, Yong Lim Kim, Daejung Kim, Jae Hyun Chang, Young Rim Song, Young-Hwan Hwang, Yon Su Kim, Curie Ahn, Joongyub Lee, Kook-Hwan Oh, Representing the Cinacalcet stUdy for Peritoneal Dialysis Patients In Double Arm on the Lowing Effect Of iPTH Level (CUPID) Study Group, Hyo Jin Kim, Hyunsuk Kim, Nara Shin, Ki Young Na, Yong Lim Kim, Daejung Kim, Jae Hyun Chang, Young Rim Song, Young-Hwan Hwang, Yon Su Kim, Curie Ahn, Joongyub Lee, Kook-Hwan Oh, Representing the Cinacalcet stUdy for Peritoneal Dialysis Patients In Double Arm on the Lowing Effect Of iPTH Level (CUPID) Study Group

Abstract

Background: Elevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients.

Objectives: The CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23.

Design: Multicenter, open-labeled, randomized controlled study.

Setting: Seven university-affiliated hospitals in Korea.

Participants: Overall, 66 peritoneal dialysis patients were enrolled.

Intervention: Sixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome.

Main outcome measures: Achievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary).

Results: 72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 ± 18.0 mg/day of cinacalcet and 0.13 ± 0.32 μg/d oral vitamin D (P < 0.001 vs. control with 0.27 ± 0.18 μg/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (- 42.54% vs. 15.83%, P = 0.008). After adjustment, cinacalcet treatment was independently associated with the serum FGF23 reduction.

Conclusion: Cinacalcet treatment was independently associated with the reduction of FGF23 in our PD patients.

Trial registration: Controlled trials NCT01101113.

Figures

Figure 1
Figure 1
Dose titration algorithm for cinacalcet and vitamin D in the cinacalcet group during dose-titration period. Initially, cinacalcet group started with 25 mg/day of cinacalcet p.o. and the cinacalcet dose was, in a stepwise pattern, increased at a 4-week interval to 50 mg/day to achieve an iPTH target between 150 and 300 pg/ml. iPTH, intact parathyroid hormone; Ca, calcium; P, phosphorus; Vit D, vitamin D.
Figure 2
Figure 2
Mineral metabolic parameters at each scheduled visit for both groups. Median iPTH (A), mean calcium-phosphorus product (Ca X P) (B), calcium (Ca) (C), and phosphorus (P) (D). iPTH decreased by 42.3% in the cinacalcet group, and by 30.7% in the control group (P = 0.483). Error bars denote interquartile range (A), or standard deviation (SD) (B, C, D). iPTH, intact parathyroid hormone; Ca, calcium; P, phosphorus.
Figure 3
Figure 3
Median percent change from baseline to final values of fibroblast growth factor (FGF23). Cinacalcet group, n = 22; Control group, n = 30. The change of FGF23 was significantly different; -42.5% vs. 15.8%, P = 0.008 as compared with control group.
Figure 4
Figure 4
Mean vitamin D dose at each time point. Error bars denote standard deviation (SD). *P < 0.05 as compared with control group.

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