NDT Advance Access originally published online on November 7, 2006
Nephrology Dialysis Transplantation 2007 22(2):362-368; doi:10.1093/ndt/gfl623
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Lanthanum carbonate decreases PTH gene expression with no hepatotoxicity in uraemic rats
1Minerva Center for Calcium and Bone Metabolism, Nephrology and Hypertension Services, 2Pathology Department, 3Radiology Department and 4Liver Unit, Hadassah—Hebrew University Medical Center, Jerusalem, Israel 91120
Correspondence and offprint requests to: Prof. Justin Silver, Minerva Center for Calcium and Bone Metabolism, Nephrology and Hypertension Services, Hadassah – Hebrew University Medical Center, Ein-Karem, PO Box 12000, Jerusalem, Israel 91120. Email: silver{at}huji.ac.il
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Abstract |
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Background. Lanthanum (La) carbonate is an effective phosphate-binder, used to reverse hyperphosphataemia due to chronic kidney disease. Some recent studies in rodents have cast safety uncertainties. The aims of this study were to examine the effects of La on parathyroid hormone (PTH) gene expression and hepatic toxicity.
Methods. Uraemia was induced in rats by a 0.3% adenine-containing diet for 2 weeks. Thereafter, rats were maintained for 4 weeks on an adenine diet with 1.5 or 3% La. Normal, uraemic, and uraemic rats fed a low-phosphorus (P) diet served as controls.
Results. Azotaemia developed in all adenine-fed rats. La of 3%, but not 1.5% La, decreased serum P to normal in uraemic rats. Both La 1.5 and 3% decreased urine P excretion. Plasma PTH was tripled in uraemic compared with normal rats. Both the 3.0% La and the low-P diet decreased PTH to normal. PTH mRNA content was increased 2-fold in uraemic compared with normal rats. The 3% La or the low-P diet decreased PTH mRNA levels to normal in uraemic rats. Liver enzymes were normal in all groups. Adenine-induced uraemia decreased liver weight with no additional effect of La. Liver weights corrected for body-weights were the same in all study groups, including the La group. Therefore, La had no effect upon absolute or corrected liver weight. Liver magnetic resonance imaging and microscopy did not reveal toxic changes due to La.
Conclusions. These findings confirm that in rats with adenine-induced uraemia, the P-binder La reverses the hyperphosphataemia and hyperparathyroidism. They are the first demonstration that La decreases PTH gene expression. Importantly, we found no evidence of drug-induced liver toxicity.
Keywords: chronic kidney disease; gene expression; hyperphosphataemia; lanthanum carbonate; phosphate binders; secondary hyperparathyroidism
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