Lanthanum carbonate decreases PTH gene expression with no hepatotoxicity in uraemic rats.
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.
Ben-Dov
Iddo Z
IZ
Minerva Center for Calcium and Bone Metabolism, Nephrology and Hypertension Services, Hadassah-Hebrew University Medical Center, Ein-Karem, PO Box 12000, Jerusalem, Israel 91120.
Pappo
Orit
O
Sklair-Levy
Miri
M
Galitzer
Hillel
H
Ilan
Yaron
Y
Naveh-Many
Tally
T
Silver
Justin
J
D000818:Animals; D001706:Biopsy; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression / Q000187:drug effects*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D007811:Lanthanum / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology
D010281:Parathyroid Hormone; C119467:lanthanum carbonate; D012313:RNA; D007811:Lanthanum