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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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Changes in (A) serum phosphorus, (B) ionized calcium and (C) calcium × phosphorus product in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. A. *P = not significant, CRF + lanthanum carbonate vs NRF groups. † P < 0.05 vs all other groups. B. *P = not significant, CRF + lanthanum carbonate vs NRF groups. P < 0.05, CRF + lanthanum carbonate vs CRF + vehicle, Week 0–22. C. *P = not significant, CRF + lanthanum carbonate vs NRF groups. P < 0.05, CRF + lanthanum carbonate vs CRF + vehicle, Week 4–22. Calcium × phosphorus product was calculated using total calcium. 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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fig2: Changes in (A) serum phosphorus, (B) ionized calcium and (C) calcium × phosphorus product in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. A. *P = not significant, CRF + lanthanum carbonate vs NRF groups. † P < 0.05 vs all other groups. B. *P = not significant, CRF + lanthanum carbonate vs NRF groups. P < 0.05, CRF + lanthanum carbonate vs CRF + vehicle, Week 0–22. C. *P = not significant, CRF + lanthanum carbonate vs NRF groups. P < 0.05, CRF + lanthanum carbonate vs CRF + vehicle, Week 4–22. Calcium × phosphorus product was calculated using total calcium. 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: Serum phosphorus, ionized calcium and calcium × phosphorus product (Ca × P) decreased slightly over time in NRF rats (Figure 2); lanthanum carbonate treatment did not significantly influence levels of these parameters. The induction of CRF resulted in significant increases in serum phosphorus and Ca × P, and a decrease in ionized calcium compared with NRF animals. When CRF rats were switched to the 0.1% adenine maintenance diet, levels improved slightly but remained abnormal. Treatment with lanthanum carbonate significantly reduced serum phosphorus (by ~ 50% vs vehicle) and increased ionized calcium such that at some time points, levels were not significantly different from those observed in NRF rats. Ca × P was also significantly reduced in CRF rats treated with lanthanum carbonate, compared with vehicle-treated controls (P < 0.05).


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) serum phosphorus, (B) ionized calcium and (C) calcium × phosphorus product in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. A. *P = not significant, CRF + lanthanum carbonate vs NRF groups. † P < 0.05 vs all other groups. B. *P = not significant, CRF + lanthanum carbonate vs NRF groups. P < 0.05, CRF + lanthanum carbonate vs CRF + vehicle, Week 0–22. C. *P = not significant, CRF + lanthanum carbonate vs NRF groups. P < 0.05, CRF + lanthanum carbonate vs CRF + vehicle, Week 4–22. Calcium × phosphorus product was calculated using total calcium. 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

fig2: Changes in (A) serum phosphorus, (B) ionized calcium and (C) calcium × phosphorus product in rats with normal renal function or chronic renal failure during 22 weeks of treatment with vehicle or lanthanum carbonate. A. *P = not significant, CRF + lanthanum carbonate vs NRF groups. † P < 0.05 vs all other groups. B. *P = not significant, CRF + lanthanum carbonate vs NRF groups. P < 0.05, CRF + lanthanum carbonate vs CRF + vehicle, Week 0–22. C. *P = not significant, CRF + lanthanum carbonate vs NRF groups. P < 0.05, CRF + lanthanum carbonate vs CRF + vehicle, Week 4–22. Calcium × phosphorus product was calculated using total calcium. 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: Serum phosphorus, ionized calcium and calcium × phosphorus product (Ca × P) decreased slightly over time in NRF rats (Figure 2); lanthanum carbonate treatment did not significantly influence levels of these parameters. The induction of CRF resulted in significant increases in serum phosphorus and Ca × P, and a decrease in ionized calcium compared with NRF animals. When CRF rats were switched to the 0.1% adenine maintenance diet, levels improved slightly but remained abnormal. Treatment with lanthanum carbonate significantly reduced serum phosphorus (by ~ 50% vs vehicle) and increased ionized calcium such that at some time points, levels were not significantly different from those observed in NRF rats. Ca × P was also significantly reduced in CRF rats treated with lanthanum carbonate, compared with vehicle-treated controls (P < 0.05).

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