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Long-term treatment with lanthanum carbonate reduces mineral and bone abnormalities in rats with chronic renal failure.

Damment S, Secker R, Shen V, Lorenzo V, Rodriguez M - Nephrol. Dial. Transplant. (2010)

Bottom Line: Lanthanum carbonate (FOSRENOL(®), Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD).Hyperphosphataemia, hypocalcaemia, elevated calcium × phosphorus product and secondary hyperparathyroidism were evident in CRF + vehicle animals.Treatment with lanthanum carbonate reduced hyperphosphataemia and secondary hyperparathyroidism in CRF animals (P < 0.05), and had little effect in NRF animals.

View Article: PubMed Central - PubMed

Affiliation: Shire Pharmaceuticals, Basingstoke, UK. sdamment@shire.com

ABSTRACT

Background: Lanthanum carbonate (FOSRENOL(®), Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). In this study, we used a rat model of chronic renal failure (CRF) to examine the long-term effects of controlling serum phosphorus with lanthanum carbonate treatment on the biochemical and bone abnormalities associated with CKD-mineral and bone disorder (CKD-MBD).

Methods: Rats were fed a normal diet (normal renal function, NRF), or a diet containing 0.75% adenine for 3 weeks to induce CRF. NRF rats continued to receive normal diet plus vehicle or normal diet supplemented with 2% (w/w) lanthanum carbonate for 22 weeks. CRF rats received a diet containing 0.1% adenine, with or without 2% (w/w) lanthanum carbonate. Blood and urine biochemistry were assessed, and bone histomorphometry was performed at study completion.

Results: Treatment with 0.75% adenine induced severe CRF, as demonstrated by elevated serum creatinine. Hyperphosphataemia, hypocalcaemia, elevated calcium × phosphorus product and secondary hyperparathyroidism were evident in CRF + vehicle animals. Treatment with lanthanum carbonate reduced hyperphosphataemia and secondary hyperparathyroidism in CRF animals (P < 0.05), and had little effect in NRF animals. Bone histomorphometry revealed a severe form of bone disease with fibrosis in CRF + vehicle animals; lanthanum carbonate treatment reduced the severity of the bone abnormalities observed, particularly woven bone formation and fibrosis.

Conclusions: Long-term treatment with lanthanum carbonate reduced the biochemical and bone abnormalities of CKD-MBD in a rat model of CRF.

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Related in: MedlinePlus

Serum PTH levels in rats with normal renal function or chronic renal failure after 22 weeks of treatment with vehicle or lanthanum carbonate. *P < 0.05 vs all other groups. NRF, normal renal function; CRF, chronic renal failure.
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fig3: Serum PTH levels in rats with normal renal function or chronic renal failure after 22 weeks of treatment with vehicle or lanthanum carbonate. *P < 0.05 vs all other groups. NRF, normal renal function; CRF, chronic renal failure.

Mentions: Levels of PTH (Figure 3) and vitamin D metabolites (Table 1) were assessed at the end of treatment; PTH levels were significantly higher in vehicle-treated CRF animals than in their NRF counterparts (mean 24-fold higher, P < 0.05). Treatment with lanthanum carbonate inhibited the increase in PTH levels: at the end of the study, mean PTH values in CRF rats treated with lanthanum carbonate were only 3-fold higher than in the NRF groups treated with lanthanum carbonate or vehicle, and the differences between these groups were not statistically significant. CRF rats had higher levels of 25-hydroxyvitamin D than NRF animals; lanthanum carbonate treatment did not significantly alter levels in CRF or NRF treatment groups. There were no statistically significant differences in 1,25-dihydroxyvitamin D levels between any treatment groups. After 22 weeks of treatment, there were no effects of lanthanum carbonate on the plasma levels of alkaline phosphatase, alanine aminotransferase or aspartate aminotransferase in CRF or NRF rats (Table 1).


Long-term treatment with lanthanum carbonate reduces mineral and bone abnormalities in rats with chronic renal failure.

Damment S, Secker R, Shen V, Lorenzo V, Rodriguez M - Nephrol. Dial. Transplant. (2010)

Serum PTH levels in rats with normal renal function or chronic renal failure after 22 weeks of treatment with vehicle or lanthanum carbonate. *P < 0.05 vs all other groups. NRF, normal renal function; CRF, chronic renal failure.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3107768&req=5

fig3: Serum PTH levels in rats with normal renal function or chronic renal failure after 22 weeks of treatment with vehicle or lanthanum carbonate. *P < 0.05 vs all other groups. NRF, normal renal function; CRF, chronic renal failure.
Mentions: Levels of PTH (Figure 3) and vitamin D metabolites (Table 1) were assessed at the end of treatment; PTH levels were significantly higher in vehicle-treated CRF animals than in their NRF counterparts (mean 24-fold higher, P < 0.05). Treatment with lanthanum carbonate inhibited the increase in PTH levels: at the end of the study, mean PTH values in CRF rats treated with lanthanum carbonate were only 3-fold higher than in the NRF groups treated with lanthanum carbonate or vehicle, and the differences between these groups were not statistically significant. CRF rats had higher levels of 25-hydroxyvitamin D than NRF animals; lanthanum carbonate treatment did not significantly alter levels in CRF or NRF treatment groups. There were no statistically significant differences in 1,25-dihydroxyvitamin D levels between any treatment groups. After 22 weeks of treatment, there were no effects of lanthanum carbonate on the plasma levels of alkaline phosphatase, alanine aminotransferase or aspartate aminotransferase in CRF or NRF rats (Table 1).

Bottom Line: Lanthanum carbonate (FOSRENOL(®), Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD).Hyperphosphataemia, hypocalcaemia, elevated calcium × phosphorus product and secondary hyperparathyroidism were evident in CRF + vehicle animals.Treatment with lanthanum carbonate reduced hyperphosphataemia and secondary hyperparathyroidism in CRF animals (P < 0.05), and had little effect in NRF animals.

View Article: PubMed Central - PubMed

Affiliation: Shire Pharmaceuticals, Basingstoke, UK. sdamment@shire.com

ABSTRACT

Background: Lanthanum carbonate (FOSRENOL(®), Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). In this study, we used a rat model of chronic renal failure (CRF) to examine the long-term effects of controlling serum phosphorus with lanthanum carbonate treatment on the biochemical and bone abnormalities associated with CKD-mineral and bone disorder (CKD-MBD).

Methods: Rats were fed a normal diet (normal renal function, NRF), or a diet containing 0.75% adenine for 3 weeks to induce CRF. NRF rats continued to receive normal diet plus vehicle or normal diet supplemented with 2% (w/w) lanthanum carbonate for 22 weeks. CRF rats received a diet containing 0.1% adenine, with or without 2% (w/w) lanthanum carbonate. Blood and urine biochemistry were assessed, and bone histomorphometry was performed at study completion.

Results: Treatment with 0.75% adenine induced severe CRF, as demonstrated by elevated serum creatinine. Hyperphosphataemia, hypocalcaemia, elevated calcium × phosphorus product and secondary hyperparathyroidism were evident in CRF + vehicle animals. Treatment with lanthanum carbonate reduced hyperphosphataemia and secondary hyperparathyroidism in CRF animals (P < 0.05), and had little effect in NRF animals. Bone histomorphometry revealed a severe form of bone disease with fibrosis in CRF + vehicle animals; lanthanum carbonate treatment reduced the severity of the bone abnormalities observed, particularly woven bone formation and fibrosis.

Conclusions: Long-term treatment with lanthanum carbonate reduced the biochemical and bone abnormalities of CKD-MBD in a rat model of CRF.

Show MeSH
Related in: MedlinePlus