Tags

Type your tag names separated by a space and hit enter

FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality.
J Clin Invest. 2012 Jul; 122(7):2543-53.JCI

Abstract

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is associated with secondary hyperparathyroidism (HPT) and serum elevations in the phosphaturic hormone FGF23, which may be maladaptive and lead to increased morbidity and mortality. To determine the role of FGF23 in the pathogenesis of CKD-MBD and development of secondary HPT, we developed a monoclonal FGF23 antibody to evaluate the impact of chronic FGF23 neutralization on CKD-MBD, secondary HPT, and associated comorbidities in a rat model of CKD-MBD. CKD-MBD rats fed a high-phosphate diet were treated with low or high doses of FGF23-Ab or an isotype control antibody. Neutralization of FGF23 led to sustained reductions in secondary HPT, including decreased parathyroid hormone, increased vitamin D, increased serum calcium, and normalization of bone markers such as cancellous bone volume, trabecular number, osteoblast surface, osteoid surface, and bone-formation rate. In addition, we observed dose-dependent increases in serum phosphate and aortic calcification associated with increased risk of mortality in CKD-MBD rats treated with FGF23-Ab. Thus, mineral disturbances caused by neutralization of FGF23 limited the efficacy of FGF23-Ab and likely contributed to the increased mortality observed in this CKD-MBD rat model.

Authors+Show Affiliations

Department of Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22728934

Citation

Shalhoub, Victoria, et al. "FGF23 Neutralization Improves Chronic Kidney Disease-associated Hyperparathyroidism yet Increases Mortality." The Journal of Clinical Investigation, vol. 122, no. 7, 2012, pp. 2543-53.
Shalhoub V, Shatzen EM, Ward SC, et al. FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality. J Clin Invest. 2012;122(7):2543-53.
Shalhoub, V., Shatzen, E. M., Ward, S. C., Davis, J., Stevens, J., Bi, V., Renshaw, L., Hawkins, N., Wang, W., Chen, C., Tsai, M. M., Cattley, R. C., Wronski, T. J., Xia, X., Li, X., Henley, C., Eschenberg, M., & Richards, W. G. (2012). FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality. The Journal of Clinical Investigation, 122(7), 2543-53. https://doi.org/10.1172/JCI61405
Shalhoub V, et al. FGF23 Neutralization Improves Chronic Kidney Disease-associated Hyperparathyroidism yet Increases Mortality. J Clin Invest. 2012;122(7):2543-53. PubMed PMID: 22728934.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality. AU - Shalhoub,Victoria, AU - Shatzen,Edward M, AU - Ward,Sabrina C, AU - Davis,James, AU - Stevens,Jennitte, AU - Bi,Vivian, AU - Renshaw,Lisa, AU - Hawkins,Nessa, AU - Wang,Wei, AU - Chen,Ching, AU - Tsai,Mei-Mei, AU - Cattley,Russell C, AU - Wronski,Thomas J, AU - Xia,Xuechen, AU - Li,Xiaodong, AU - Henley,Charles, AU - Eschenberg,Michael, AU - Richards,William G, Y1 - 2012/06/25/ PY - 2011/10/11/received PY - 2012/05/10/accepted PY - 2012/6/26/entrez PY - 2012/6/26/pubmed PY - 2012/9/12/medline SP - 2543 EP - 53 JF - The Journal of clinical investigation JO - J Clin Invest VL - 122 IS - 7 N2 - Chronic kidney disease-mineral and bone disorder (CKD-MBD) is associated with secondary hyperparathyroidism (HPT) and serum elevations in the phosphaturic hormone FGF23, which may be maladaptive and lead to increased morbidity and mortality. To determine the role of FGF23 in the pathogenesis of CKD-MBD and development of secondary HPT, we developed a monoclonal FGF23 antibody to evaluate the impact of chronic FGF23 neutralization on CKD-MBD, secondary HPT, and associated comorbidities in a rat model of CKD-MBD. CKD-MBD rats fed a high-phosphate diet were treated with low or high doses of FGF23-Ab or an isotype control antibody. Neutralization of FGF23 led to sustained reductions in secondary HPT, including decreased parathyroid hormone, increased vitamin D, increased serum calcium, and normalization of bone markers such as cancellous bone volume, trabecular number, osteoblast surface, osteoid surface, and bone-formation rate. In addition, we observed dose-dependent increases in serum phosphate and aortic calcification associated with increased risk of mortality in CKD-MBD rats treated with FGF23-Ab. Thus, mineral disturbances caused by neutralization of FGF23 limited the efficacy of FGF23-Ab and likely contributed to the increased mortality observed in this CKD-MBD rat model. SN - 1558-8238 UR - https://www.unboundmedicine.com/medline/citation/22728934/FGF23_neutralization_improves_chronic_kidney_disease_associated_hyperparathyroidism_yet_increases_mortality_ L2 - https://doi.org/10.1172/JCI61405 DB - PRIME DP - Unbound Medicine ER -