Efficacy of Combined CHAp and Lanthanum Carbonate in Therapy for Hyperphosphatemia

Authors: Andreea Cârâc, Elena Moroşan, Ana Corina Ioniță, Rica Boscencu, Geta Cârâc

Abstract:

Although, lanthanum carbonate has not been approved by the FDA for treatment of hyperphosphatemia, we prospectively evaluated the efficacy of the combination of Calcium hydroxyapatite (CHAp) and Lanthanum Carbonate (LaC) for the treatment of hyperphosphatemia on mice. CHAp was prepared by co-precipitation method using Ca(OH)2, H3PO4, NH4OH with calcination at 1200ºC. Lanthanum carbonate was prepared by chemical method using NaHCO3 and LaCl3 at low pH environment, below 4.0. The structures were characterized by FTIR spectra and SEM -EDX analysis. The study group included 16 subjects-mice divided into four groups according to the administered substance: lanthanum carbonate (group A), CHAp (group B), lanthanum carbonate + CHAp (group C) and salt water (group D). The results indicate a phosphate decrease when subjects (mice) were treated with CHAp and lanthanum carbonate (0.5% CMC), in a single dose of 1500 mg/kg. Serum phosphate concentration decreased [(from 4.5 ± 0.8 mg/dL) to 4.05 ± 0.2 mg/dL), P < 0.01] in group A and in group C (to 3.6 ± 0.2 mg/dL) at 12 hours from the administration. The combination of CHAp and lanthanum carbonate is a suitable regimen for hyperphosphatemia treatment because it avoids both the hypercalcemia of CaCO3 and the adverse effects of CHAp.

Keywords: Calcium hydroxyapatite, hyperphosphatemia, lanthanum carbonate, phosphatebinder, structures.

Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1100723

References:

[1] S. Damment, “Pharmacology of the Phosphate Binder, Lanthanum Carbonate”, Laboratory Studies, vol. 33, no. 2, pp. 217-224, 2011.
[2] V. P. Persy, G. J. Behets, A. R. Bervoets, M. E. De Broe, P. C. D’Haese, “Lanthanum: a safe phosphate binder”, Semin Dial, vol. 19, pp. 195-199, 2006.
[3] J. Pairon, F. Roos, P. Sebastien, B. Chamak, I. Abd-alsamad, J. Bernaudin, J. Bignon, P. Brochard, “Biopersistence of cerium in the human respiratory tract and ultrastructural findings”, Am. J. Ind. Med. vol. 27, pp. 349-358, 1995.
[4] A. J. Hutchison, M. E. Barnett, R. J. Krause, G. A. Siami, “Lanthanum carbonate treatment, for up to 6 years, is not associated with adverse effects on the liver in patients with chronic kidney disease Stage 5 receiving hemodialysis”, Clin. Nephrol., vol. 7, no. 3, pp. 286-295, 2009.
[5] S. M. Sprague, H. Abboud, P. Qiu, M. Dauphin, P. Zhang, W. Finn. “Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial”, Clin J Am Soc Nephrol, vol. 4, pp. 178-185, 2009.
[6] A. J. Hutchison, M. E. Barnett, R. Krause, J. T. Kwan, G. A. Siami, “Lanthanum Study Group Long-term efficacy and safety profile of lanthanum carbonate: Results for up to 6 years of treatment”, Nephron Clin Pract., vol. 110, no. 1, pp. c15-23, 2008.
[7] G. J. Behets, G. Dams, S. R. Vercauteren, S. J. Damment, R. Bouillon, M. E. De Broe, P. C. D’Haese, “Does the phosphate binder lanthanum carbonate affect bone in rats with chronic renal failure?”, J. Am. Soc. Nephrol., vol. 15, pp. 2219-2228, 2004.
[8] T. Shigematsu, Y. Nakashima, M. Ohya, Tatsuta K., Koreeda D., Yoshimoto W., Yamanaska S., Sakaguchi T., Hanba Y., Mima T., Negi “The management of hyperphosphatemia by lanthanum carbonate in chronic kidney disease patients”, Inter. J. of Nephrology and Renovascular Disease, May 2012.
[9] I. Mohammed, A. Hutchison, “Phosphate binding therapy in dialysis patients: focus on lanthanum carbonate”, Ther. Clin. Risk Manag., vol 4, no. 5, pp. 887-893, 2008.
[10] W. F. Finn, “Lanthanum carbonate versus standard therapy for the treatment of hyperphosphatemia: safety and efficacy in chronic maintenance hemodialysis patients”, Clin. Nephrol., vol. 65, pp. 191- 202, 2006.
[11] A. J. Hutchison, F. Al-Baaj, “Lanthanum carbonate for the treatment of hyperphosphatemia in renal failure and dialysis patients”, Expert Opin. Pharmacother., vol. 6, pp. 319-28, 2005.
[12] G.J. Behets, G. Dams, S.J. Damment, P. Martin, M. E. Broe, De, D'Haese, “Differences in gastrointestinal calcium absorption after the ingestion of calcium-free phosphate binders”, American Journal of Physiology - Renal Physiology, vol.306, no. 1, pp. F61-F67, 2014.
[13] A. Palasz, P. Czekaj, “Toxicological and cytophysiological aspects of lanthanides action”, II Department of Histology and Embryology, Silesian Medical Academy, Katowice, Poland, vol. 47, no. 4, pp. 1107- 1114, 2000.
[14] Z. Deng, L. Wang, D. Zhang, J. Liu, C. Liu, J. Ma, “Lanthanumcontaining hydroxyapatite coating on ultrafine-grained titanium by micro-arc oxidation: A promising strategy to enhance overall performance of titanium”, Med. Sci. Monit., vol. 20, pp. 163-166, 2014.
[15] D. G. Guo, A. H. Wang, Y. Han, K. W. Xu, “Characterization, physicochemical properties and biocompatibility of La-incorporated apatites”, Acta Biomater. vol. 5, no. 9, pp. 3512-3523, November. 2009.
[16] J.C. Zhang, T.L. Zhang, S.J. Xu, K. Wang, S.F. Yu, “Effects of lanthanum on formation and bone-resorbing activity of osteoclast-like cells”, J. Rare Earths, vol. 22, no. 6, pp. 891-895, 2004.
[17] H. Hayashi, M. Machida, T. Sekine., H. Yamaguchi, Kiriyama, T. Kumita S., “Beam-hardening artifacts on computed tomography images caused by lanthanum carbonate hydrate in a patient on dialysis”, Jpn. J. Radiol., vol. 28, no. 4, pp. 322-324, May 2010.
[18] G. N. Nadkarni, J. Uribarri, “Phosphorus and the kidney: what is known and what is needed”, Adv. Nutr., vol. 5, pp. 98-103, 2014.