FGF23 Neutralization Improves Chronic Kidney Disease-associated Hyperparathyroidism Yet Increases Mortality

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2012 Jun 26

PMID 22728934

Citations 187

Authors

Victoria Shalhoub

Edward M Shatzen

Sabrina C Ward

James Davis

Jennitte Stevens

Vivian Bi

Lisa Renshaw

Nessa Hawkins

Wei Wang

Ching Chen

Mei-Mei Tsai

Russell C Cattley

Thomas J Wronski

Xuechen Xia

Xiaodong Li

Charles Henley

Michael Eschenberg

William G Richards

Affiliations

Soon will be listed here.

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.

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