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Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels.
Br J Pharmacol 2009; 156(8):1267-78BJ

Abstract

BACKGROUND AND PURPOSE

Various complications consequent on disordered calcium and phosphate homeostasis occur frequently in chronic kidney disease (CKD) patients. Particularly, vascular calcification has high morbidity and mortality rates. There is a clear need for a better CKD model to examine various aspects of this disordered homeostasis.

EXPERIMENTAL APPROACH

Oral dosing with adenine induced CKD in rats in only 10 days. Serum calcium, phosphate and parathyroid hormone were measured and calcification in aorta was assessed histologically. The effects of varying phosphorus content of diet or treatment with phosphate binders or active vitamin D(3) on these parameters were examined.

KEY RESULTS

After adenine dosing, significant hyperphosphatemia, hypocalcemia and secondary hyperparathyroidism (2HPT) were observed during the experimental period of 15 weeks. Aortic calcification was detected in only some of the animals even at 15 weeks (approximately 40%). Treatment with vitamin D(3) for 18 days, even at a low dose (100 ng x kg(-1), 3-4 times week(-1), p.o), caused aortic calcification in all animals and increases in serum calcium levels up to the normal range. The vitamin D(3)-induced calcification was significantly inhibited by phosphate binders which lowered serum phosphate levels and the calcium x phosphate product, although serum calcium levels were elevated.

CONCLUSIONS

These data suggest that rats dosed orally with adenine provide a more useful model for analysing calcium/phosphate homeostasis in severe CKD. Controlling serum calcium/phosphate levels with phosphate binders may be better than vitamin D(3) treatment in hyperphosphatemia and 2HPT, to avoid vascular calcification.

Authors+Show Affiliations

Diabetic Complications Department, Pharmacology Research Lab., Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan. kazuhiro.terai@jp.astellas.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19302594

Citation

Terai, K, et al. "Vascular Calcification and Secondary Hyperparathyroidism of Severe Chronic Kidney Disease and Its Relation to Serum Phosphate and Calcium Levels." British Journal of Pharmacology, vol. 156, no. 8, 2009, pp. 1267-78.
Terai K, Nara H, Takakura K, et al. Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels. Br J Pharmacol. 2009;156(8):1267-78.
Terai, K., Nara, H., Takakura, K., Mizukami, K., Sanagi, M., Fukushima, S., ... Okada, M. (2009). Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels. British Journal of Pharmacology, 156(8), pp. 1267-78. doi:10.1111/j.1476-5381.2008.00108.x.
Terai K, et al. Vascular Calcification and Secondary Hyperparathyroidism of Severe Chronic Kidney Disease and Its Relation to Serum Phosphate and Calcium Levels. Br J Pharmacol. 2009;156(8):1267-78. PubMed PMID: 19302594.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vascular calcification and secondary hyperparathyroidism of severe chronic kidney disease and its relation to serum phosphate and calcium levels. AU - Terai,K, AU - Nara,H, AU - Takakura,K, AU - Mizukami,K, AU - Sanagi,M, AU - Fukushima,S, AU - Fujimori,A, AU - Itoh,H, AU - Okada,M, Y1 - 2009/03/19/ PY - 2009/3/24/entrez PY - 2009/3/24/pubmed PY - 2010/1/6/medline SP - 1267 EP - 78 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 156 IS - 8 N2 - BACKGROUND AND PURPOSE: Various complications consequent on disordered calcium and phosphate homeostasis occur frequently in chronic kidney disease (CKD) patients. Particularly, vascular calcification has high morbidity and mortality rates. There is a clear need for a better CKD model to examine various aspects of this disordered homeostasis. EXPERIMENTAL APPROACH: Oral dosing with adenine induced CKD in rats in only 10 days. Serum calcium, phosphate and parathyroid hormone were measured and calcification in aorta was assessed histologically. The effects of varying phosphorus content of diet or treatment with phosphate binders or active vitamin D(3) on these parameters were examined. KEY RESULTS: After adenine dosing, significant hyperphosphatemia, hypocalcemia and secondary hyperparathyroidism (2HPT) were observed during the experimental period of 15 weeks. Aortic calcification was detected in only some of the animals even at 15 weeks (approximately 40%). Treatment with vitamin D(3) for 18 days, even at a low dose (100 ng x kg(-1), 3-4 times week(-1), p.o), caused aortic calcification in all animals and increases in serum calcium levels up to the normal range. The vitamin D(3)-induced calcification was significantly inhibited by phosphate binders which lowered serum phosphate levels and the calcium x phosphate product, although serum calcium levels were elevated. CONCLUSIONS: These data suggest that rats dosed orally with adenine provide a more useful model for analysing calcium/phosphate homeostasis in severe CKD. Controlling serum calcium/phosphate levels with phosphate binders may be better than vitamin D(3) treatment in hyperphosphatemia and 2HPT, to avoid vascular calcification. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/19302594/Vascular_calcification_and_secondary_hyperparathyroidism_of_severe_chronic_kidney_disease_and_its_relation_to_serum_phosphate_and_calcium_levels_ L2 - https://doi.org/10.1111/j.1476-5381.2008.00108.x DB - PRIME DP - Unbound Medicine ER -