Limits...
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

Lanthanum is localized in lysosomes at the biliary pole of hepatocytes. Transmission electron microscopy image of liver tissue of La loaded rat (dose: 0.3 mg/kg/day IV, 4 weeks) showing electron dense precipitates displaying a crystalline granular structure within the lysosomes and bile canaliculus. The presence of lanthanum in these granular structures was evidenced by electron energy loss spectroscopy (EELS). Adapted with permission from Macmillan Publishers, Ltd. Kidney Int. Bervoets AR, Behets GJ, Schryvers D, et al. 2009;75(4):389–398. Copyright © 2008.62
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3108761&req=5

f3-ijnrd-2-001: Lanthanum is localized in lysosomes at the biliary pole of hepatocytes. Transmission electron microscopy image of liver tissue of La loaded rat (dose: 0.3 mg/kg/day IV, 4 weeks) showing electron dense precipitates displaying a crystalline granular structure within the lysosomes and bile canaliculus. The presence of lanthanum in these granular structures was evidenced by electron energy loss spectroscopy (EELS). Adapted with permission from Macmillan Publishers, Ltd. Kidney Int. Bervoets AR, Behets GJ, Schryvers D, et al. 2009;75(4):389–398. Copyright © 2008.62

Mentions: To enable subcellular localization of lanthanum in liver tissue, rats received daily intravenous injections with 0.3 mg/kg lanthanum chloride for 4 weeks, leading to liver lanthanum concentrations of 30 to 50 μg/g (10- to 20-fold higher than values seen after oral lanthanum loading). Sensitive techniques such as transmission electron microscopy (TEM), Energy dispersive X-ray analysis (EDX) and electron loss spectroscopy (EELS) were used to demonstrate that lanthanum in the liver of these animals was present in the lysosomes of hepatocytes, with most of the lanthanum concentrated in the biliary pole of the hepatocyte and within bile canaliculi. No lanthanum could be detected in hepatocyte mitochondria, nucleus or cytoplasm (Figure 3).63


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)

Lanthanum is localized in lysosomes at the biliary pole of hepatocytes. Transmission electron microscopy image of liver tissue of La loaded rat (dose: 0.3 mg/kg/day IV, 4 weeks) showing electron dense precipitates displaying a crystalline granular structure within the lysosomes and bile canaliculus. The presence of lanthanum in these granular structures was evidenced by electron energy loss spectroscopy (EELS). Adapted with permission from Macmillan Publishers, Ltd. Kidney Int. Bervoets AR, Behets GJ, Schryvers D, et al. 2009;75(4):389–398. Copyright © 2008.62
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijnrd-2-001: Lanthanum is localized in lysosomes at the biliary pole of hepatocytes. Transmission electron microscopy image of liver tissue of La loaded rat (dose: 0.3 mg/kg/day IV, 4 weeks) showing electron dense precipitates displaying a crystalline granular structure within the lysosomes and bile canaliculus. The presence of lanthanum in these granular structures was evidenced by electron energy loss spectroscopy (EELS). Adapted with permission from Macmillan Publishers, Ltd. Kidney Int. Bervoets AR, Behets GJ, Schryvers D, et al. 2009;75(4):389–398. Copyright © 2008.62
Mentions: To enable subcellular localization of lanthanum in liver tissue, rats received daily intravenous injections with 0.3 mg/kg lanthanum chloride for 4 weeks, leading to liver lanthanum concentrations of 30 to 50 μg/g (10- to 20-fold higher than values seen after oral lanthanum loading). Sensitive techniques such as transmission electron microscopy (TEM), Energy dispersive X-ray analysis (EDX) and electron loss spectroscopy (EELS) were used to demonstrate that lanthanum in the liver of these animals was present in the lysosomes of hepatocytes, with most of the lanthanum concentrated in the biliary pole of the hepatocyte and within bile canaliculi. No lanthanum could be detected in hepatocyte mitochondria, nucleus or cytoplasm (Figure 3).63

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