Limits...
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.

Show MeSH

Related in: MedlinePlus

Changes in serum creatinine in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. *P < 0.05 vs all other groups. Data are presented as mean ± standard error of the mean. NRF, normal renal function; CRF, chronic renal failure. Dashed vertical line indicates initiation of vehicle or lanthanum carbonate treatment.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3107768&req=5

fig1: Changes in serum creatinine in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. *P < 0.05 vs all other groups. Data are presented as mean ± standard error of the mean. NRF, normal renal function; CRF, chronic renal failure. Dashed vertical line indicates initiation of vehicle or lanthanum carbonate treatment.

Mentions: Blood biochemistry was assessed before induction of CRF (Week − 3), at the end of disease induction (Week 0) and during the subsequent 22 weeks of treatment. At the end of disease induction, serum creatinine was significantly higher in CRF rats than in NRF animals (P < 0.05). During the subsequent 22 weeks of treatment, serum creatinine remained elevated in CRF rats, but levels were lower in those treated with lanthanum carbonate than in vehicle-treated controls (P < 0.05 for creatinine at Week 22, Figure 1). The addition of lanthanum carbonate to the diet of NRF animals did not affect creatinine levels.


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)

Changes in serum creatinine in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. *P < 0.05 vs all other groups. Data are presented as mean ± standard error of the mean. NRF, normal renal function; CRF, chronic renal failure. Dashed vertical line indicates initiation of vehicle or lanthanum carbonate treatment.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

fig1: Changes in serum creatinine in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. *P < 0.05 vs all other groups. Data are presented as mean ± standard error of the mean. NRF, normal renal function; CRF, chronic renal failure. Dashed vertical line indicates initiation of vehicle or lanthanum carbonate treatment.
Mentions: Blood biochemistry was assessed before induction of CRF (Week − 3), at the end of disease induction (Week 0) and during the subsequent 22 weeks of treatment. At the end of disease induction, serum creatinine was significantly higher in CRF rats than in NRF animals (P < 0.05). During the subsequent 22 weeks of treatment, serum creatinine remained elevated in CRF rats, but levels were lower in those treated with lanthanum carbonate than in vehicle-treated controls (P < 0.05 for creatinine at Week 22, Figure 1). The addition of lanthanum carbonate to the diet of NRF animals did not affect creatinine levels.

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