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Management of hyperphosphatemia in patients with end-stage renal disease: focus on lanthanum carbonate.

Persy VP, Behets GJ, De Broe ME, D'Haese PC - Int J Nephrol Renovasc Dis (2009)

Bottom Line: Although lanthanum is a metal cation no aluminium-like toxicity is observed since the bioavailability of lanthanum is extremely low and its metabolism differs from that of aluminium.Clinical studies now document the absence of toxic effects of lanthanum for up to 6 years of follow-up.The effects of lanthanum on bone, vasculature and brain are discussed and put in perspective with lanthanum pharmacokinetics.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathophysiology, University of Antwerp, Belgium.

ABSTRACT
Elevated serum phosphate levels as a consequence of chronic kidney disease (CKD) contribute to the increased cardiovascular risk observed in dialysis patients. Protein restriction and dialysis fail to adequately prevent hyperphosphatemia, and in general treatment with oral phosphate binding agents is necessary in patients with advanced CKD. Phosphate plays a pivotal role in the development of vascular calcification, one of the factors contributing to increased cardiovascular risk in CKD patients. Treatment of hyperphosphatemia with standard calcium-based phosphate binders and vitamin D compounds can induce hypercalcemic episodes, increase the Ca × PO(4) product and thus add to the risk of ectopic mineralization. In this review, recent clinical as well as experimental data on lanthanum carbonate, a novel, non-calcium, non-resin phosphate binding agent are summarized. Although lanthanum is a metal cation no aluminium-like toxicity is observed since the bioavailability of lanthanum is extremely low and its metabolism differs from that of aluminium. Clinical studies now document the absence of toxic effects of lanthanum for up to 6 years of follow-up. The effects of lanthanum on bone, vasculature and brain are discussed and put in perspective with lanthanum pharmacokinetics.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of lanthanum localization in bone. With micro X-ray fluorescence, lanthanum was found at active bone formation and resorption sites, as well as on quiescent bone surfaces and dispersed throughout the mineralized matrix. Lanthanum concentrations in proximity to resorption lacunae probably reflect lanthanum uptake in osteoclasts or macrophages.58 Adapted with permission from Persy VP et al. Semin Dial. 2006;19(3):195–199.59 Copyright © 2006 Blackwell Publishing.
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f2-ijnrd-2-001: Schematic representation of lanthanum localization in bone. With micro X-ray fluorescence, lanthanum was found at active bone formation and resorption sites, as well as on quiescent bone surfaces and dispersed throughout the mineralized matrix. Lanthanum concentrations in proximity to resorption lacunae probably reflect lanthanum uptake in osteoclasts or macrophages.58 Adapted with permission from Persy VP et al. Semin Dial. 2006;19(3):195–199.59 Copyright © 2006 Blackwell Publishing.

Mentions: Toxic effects strongly depend on local concentrations in target tissue and cells, whereas physicochemical interference with mineralization on the level of hydroxyapatite nucleation, crystal growth or structure strongly depends on the molar ratio of an element over calcium. Lanthanum localization studies have not revealed any indication that lanthanum would selectively concentrate at particular sites or cell types in bone. Localization of lanthanum carbonate in bone with micro X-ray fluorescence demonstrated the presence of lanthanum at both active and quiescent trabecular surface, independent of the type of underlying ROD. In addition, lanthanum could be detected distributed diffusely throughout the mineralized matrix, especially in subjects with increased bone turnover, and concentrated close to resorption lacunae, probably in osteoclasts or macrophages (Figure 2).58


Management of hyperphosphatemia in patients with end-stage renal disease: focus on lanthanum carbonate.

Persy VP, Behets GJ, De Broe ME, D'Haese PC - Int J Nephrol Renovasc Dis (2009)

Schematic representation of lanthanum localization in bone. With micro X-ray fluorescence, lanthanum was found at active bone formation and resorption sites, as well as on quiescent bone surfaces and dispersed throughout the mineralized matrix. Lanthanum concentrations in proximity to resorption lacunae probably reflect lanthanum uptake in osteoclasts or macrophages.58 Adapted with permission from Persy VP et al. Semin Dial. 2006;19(3):195–199.59 Copyright © 2006 Blackwell Publishing.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108761&req=5

f2-ijnrd-2-001: Schematic representation of lanthanum localization in bone. With micro X-ray fluorescence, lanthanum was found at active bone formation and resorption sites, as well as on quiescent bone surfaces and dispersed throughout the mineralized matrix. Lanthanum concentrations in proximity to resorption lacunae probably reflect lanthanum uptake in osteoclasts or macrophages.58 Adapted with permission from Persy VP et al. Semin Dial. 2006;19(3):195–199.59 Copyright © 2006 Blackwell Publishing.
Mentions: Toxic effects strongly depend on local concentrations in target tissue and cells, whereas physicochemical interference with mineralization on the level of hydroxyapatite nucleation, crystal growth or structure strongly depends on the molar ratio of an element over calcium. Lanthanum localization studies have not revealed any indication that lanthanum would selectively concentrate at particular sites or cell types in bone. Localization of lanthanum carbonate in bone with micro X-ray fluorescence demonstrated the presence of lanthanum at both active and quiescent trabecular surface, independent of the type of underlying ROD. In addition, lanthanum could be detected distributed diffusely throughout the mineralized matrix, especially in subjects with increased bone turnover, and concentrated close to resorption lacunae, probably in osteoclasts or macrophages (Figure 2).58

Bottom Line: Although lanthanum is a metal cation no aluminium-like toxicity is observed since the bioavailability of lanthanum is extremely low and its metabolism differs from that of aluminium.Clinical studies now document the absence of toxic effects of lanthanum for up to 6 years of follow-up.The effects of lanthanum on bone, vasculature and brain are discussed and put in perspective with lanthanum pharmacokinetics.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pathophysiology, University of Antwerp, Belgium.

ABSTRACT
Elevated serum phosphate levels as a consequence of chronic kidney disease (CKD) contribute to the increased cardiovascular risk observed in dialysis patients. Protein restriction and dialysis fail to adequately prevent hyperphosphatemia, and in general treatment with oral phosphate binding agents is necessary in patients with advanced CKD. Phosphate plays a pivotal role in the development of vascular calcification, one of the factors contributing to increased cardiovascular risk in CKD patients. Treatment of hyperphosphatemia with standard calcium-based phosphate binders and vitamin D compounds can induce hypercalcemic episodes, increase the Ca × PO(4) product and thus add to the risk of ectopic mineralization. In this review, recent clinical as well as experimental data on lanthanum carbonate, a novel, non-calcium, non-resin phosphate binding agent are summarized. Although lanthanum is a metal cation no aluminium-like toxicity is observed since the bioavailability of lanthanum is extremely low and its metabolism differs from that of aluminium. Clinical studies now document the absence of toxic effects of lanthanum for up to 6 years of follow-up. The effects of lanthanum on bone, vasculature and brain are discussed and put in perspective with lanthanum pharmacokinetics.

No MeSH data available.


Related in: MedlinePlus