Back to Search
Start Over
Lanthanum carbonate decreases PTH gene expression with no hepatotoxicity in uraemic rats.
- Source :
-
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association [Nephrol Dial Transplant] 2007 Feb; Vol. 22 (2), pp. 362-8. Date of Electronic Publication: 2006 Nov 07. - Publication Year :
- 2007
-
Abstract
- 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.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Biopsy
Disease Models, Animal
Disease Progression
Kidney Failure, Chronic blood
Kidney Failure, Chronic etiology
Kidney Failure, Chronic prevention & control
Lanthanum pharmacokinetics
Liver drug effects
Liver pathology
Magnetic Resonance Imaging
Male
Parathyroid Hormone blood
Polymerase Chain Reaction
Rats
Rats, Sprague-Dawley
Uremia blood
Uremia etiology
Gene Expression drug effects
Lanthanum therapeutic use
Liver metabolism
Parathyroid Hormone genetics
RNA genetics
Uremia drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0931-0509
- Volume :
- 22
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
- Publication Type :
- Academic Journal
- Accession number :
- 17090605
- Full Text :
- https://doi.org/10.1093/ndt/gfl623