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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

Changes in (A) urinary phosphorus and (B) urinary calcium excretion in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. A. P < 0.05 NRF + lanthanum carbonate vs NRF + vehicle, Week 4–22. P < 0.05 CRF + lanthanum carbonate vs CRF + vehicle, Week 4–22. B. P < 0.05 CRF + lanthanum carbonate vs CRF + vehicle, Week 4–12. 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.
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fig4: Changes in (A) urinary phosphorus and (B) urinary calcium excretion in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. A. P < 0.05 NRF + lanthanum carbonate vs NRF + vehicle, Week 4–22. P < 0.05 CRF + lanthanum carbonate vs CRF + vehicle, Week 4–22. B. P < 0.05 CRF + lanthanum carbonate vs CRF + vehicle, Week 4–12. 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: Lanthanum carbonate treatment resulted in a decrease in urinary phosphorus excretion and an increase in urinary calcium excretion compared with vehicle-treated controls (Figure 4). Indeed, in CRF rats, treatment with lanthanum carbonate reduced urinary phosphorus excretion by ~ 40% compared with vehicle-treated animals (P < 0.05); this reduction was maintained throughout the study.


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 (A) urinary phosphorus and (B) urinary calcium excretion in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. A. P < 0.05 NRF + lanthanum carbonate vs NRF + vehicle, Week 4–22. P < 0.05 CRF + lanthanum carbonate vs CRF + vehicle, Week 4–22. B. P < 0.05 CRF + lanthanum carbonate vs CRF + vehicle, Week 4–12. 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

fig4: Changes in (A) urinary phosphorus and (B) urinary calcium excretion in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. A. P < 0.05 NRF + lanthanum carbonate vs NRF + vehicle, Week 4–22. P < 0.05 CRF + lanthanum carbonate vs CRF + vehicle, Week 4–22. B. P < 0.05 CRF + lanthanum carbonate vs CRF + vehicle, Week 4–12. 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: Lanthanum carbonate treatment resulted in a decrease in urinary phosphorus excretion and an increase in urinary calcium excretion compared with vehicle-treated controls (Figure 4). Indeed, in CRF rats, treatment with lanthanum carbonate reduced urinary phosphorus excretion by ~ 40% compared with vehicle-treated animals (P < 0.05); this reduction was maintained throughout the study.

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