Abstract

Objectives: The aim of this study was to determine the differential dose response of parathyroid hormone (PTH) and fibroblast growth factor (FGF23) to paricalcitol in patients with secondary hyperparathyroidism and end-stage renal failure on chronic intermittent hemodialysis.
Materials and methods: The multicenter, randomized, double-blind, prospective, crossover study comprised a total of 43 hemodialysis patients (average age 64 years, female 30%) with 31 complete patient data sets, and with PTH levels between 200 and 600 pg/mL, serum calcium < 2.55 mmol/L, phosphorus ≤ 2.1 mmol/L, and 25 OH-vitamin D > 20 ng/mL as inclusion criteria (Eudract 2007-006606-16).
Results: Mean intact PTH at baseline was 319 pg/mL (standard deviation (SD) 141, normal 11.3 – 42.4 pg/mL; ECLIA; Roche, Basel, Switzerland) and FGF23 651.25 RU/mL (SD 1,099.98; normal 21 – 424 RU/mL; c-terminal, 2^nd generation ELISA kit, Immutopics, San Clemente, CA, USA) at baseline. The initial oral dose of paricalcitol was 2 μg/day, adjusted to a mean dosage of 1.9 μg/day at week 6 and 1.5 μg/day at week 12, guided by PTH response. PTH levels remained significantly suppressed at both 6 (189 pg/mL; SD 95) and 12 weeks (164 pg/mL; SD 95), both p < 0.001 as compared to baseline. FGF23 levels showed a significant increase at 6 weeks (1,442.1 RU/mL, SD 1,860.2; p = 0.002) but returned at 12 weeks to levels not significantly different from baseline (1,150.7 RU/mL, SD 1,509.3; p = 0.24).
Conclusion: Treatment with paricalcitol resulted in a significant reduction in PTH levels at both 6 and 12 weeks compared to placebo. The suppression of PTH levels with paricalcitol was possible without elevating FGF23 within the restrictions of this short duration study, at least if over-suppression of PTH is avoided by dose adaption. Our findings suggest a cautious lower oral paricalcitol starting dose to mitigate the initial spike in FGF23 while effectively managing PTH levels.

Author Details

Authors

• Nicolaus Mussmaecher¹
• Steffen Mitzner²
• Christian Haas³
• Martin Busch⁴
• Markus Ketteler⁵
• Christoph Wanner⁶
• Patrick Biggar⁷

Departments

• ¹ Department of Radiology and Nuclear Medicine, Luzerner Kantonsspital, Zentrumsspital, Luzern, Switzerland,
• ² Division of Nephrology and Fraunhofer Institute for Cell Therapy and Immunology,
• ³ Division of Nephrology, Department of Medicine, University Hospital Rostock, Rostock,
• ⁴ Department of Internal Medicine III, University Hospital Jena, Friedrich-Schiller University, Jena,
• ⁵ Department of General Medicine and Nephrology, Robert-Bosch Hospital, Stuttgart,
• ⁶ Medical Clinic and Polyclinic I, University Hospital Wuerzburg, and
• ⁷ KfH Kidney Center, Kulmbach, Germany

Address

Dr. Patrick Biggar
KfH Kidney Center
Melkendorfer Strasse 8A
95326 Kulmbach, Germany
Email: [email protected]

Citation