Special Report
Phosphate Homeostasis in CKD: Report of a Scientific Symposium Sponsored by the National Kidney Foundation

https://doi.org/10.1053/j.ajkd.2013.03.042Get rights and content

Chronic kidney disease (CKD)–mineral and bone disorder is associated with diverse metabolic and endocrine disturbances that ultimately may contribute to further loss of kidney function, bone demineralization, and fatal or nonfatal cardiovascular events. Recent insights into the pathophysiology of the events that unfold during the development of this disorder suggest that disturbances in phosphate metabolism are pivotal. The consequences of abnormal phosphate homeostasis are evident at estimated glomerular filtration rates <70 mL/min/1.73 m2, long before serum phosphate levels increase. Healthy individuals with blood phosphate levels in the top quartile of the normal range have an increased risk of developing CKD, reaching end-stage renal disease, and experiencing cardiovascular events. Substantial public health consequences may be related to increased dietary phosphorus exposure from additives that contain phosphate in the food supply and from modest increases in serum phosphate levels; however, it remains to be established whether interventions aimed at these targets can impact on the development of adverse clinical outcomes. Current approaches involving dietary intervention and intestinal phosphate binders are based on principles and assumptions that need to be examined more rigorously. Compelling animal, observational, and clinical data indicate that interventions directed at lowering phosphate exposure and serum phosphate levels should be subject to rigorous clinical trials that use appropriate placebo comparators and focus on key clinical outcomes, such as cardiovascular events, progression of CKD, fractures, quality of life, and mortality.

Section snippets

Overview

Despite guidelines recommending the restriction of dietary phosphorus in patients with CKD who manifest hyperphosphatemia or secondary hyperparathyroidism, there are few data that directly address the relationship between dietary phosphorus intake and clinical outcomes in CKD. Furthermore, the ability of dietary phosphorus modification to alter serum phosphate levels in patients with CKD has not been studied adequately. It is common to describe CKD as a state of phosphate “overload”; however,

Overview

The limited ability of interventions to reduce serum phosphate levels highlights the limitations of what is known regarding phosphate regulation. Phosphorus is an essential element for multiple cellular functions, including cell membrane structure, energy metabolism, protein modification, and as a second messenger. As such, there are duplicative mechanisms to conserve phosphate. Under stable conditions, the key determinants of phosphate balance are intestinal phosphate absorption, skeletal bone

Clinical Trial Design

The consistency of the in vitro, animal, observational, and human data certainly indicate that clinical trials aimed at intervening in phosphate regulation in an attempt to modify clinical outcomes in patients with CKD are warranted. Multiple studies have demonstrated that higher serum phosphate concentrations are associated with CVD events, CVD-related death, and all-cause death.15, 19, 23, 90, 91 Some of the available studies suggest that the relationship of higher phosphate concentrations

Summary

A substantial body of evidence suggests that disordered phosphate homeostasis is central to CKD-MBD. Phosphate dysregulation begins early in the course of CKD and is associated with maladaptive CV changes and loss of bone structural integrity. Clinical consequences may include further loss of kidney function, CV events, and fractures. These disturbances in phosphate metabolism, which do not necessarily lead to an increase in total-body phosphate, are mediated by a series of complex changes to

Acknowledgements

The NKF acknowledges CM&D Pharma, Cytochroma, Sanofi, and Vifor for their support of the conference; Kerry Willis, PhD, and Tom Manley of the NKF, who assisted in meeting logistics and manuscript preparation; and Doug Chauncey at XTEC media, who assisted with graphic design.

Conference participants are as follows. Stephen Appelbee, London, UK; Joseph Bender, MD, Cambridge, MA; Geoffrey Block, MD, Denver, CO; Mona Calvo, PhD, Laurel, MD; Ricardo Carvajal, MS, JD, Washington, DC; Dolph

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    Originally published online June 13, 2013.

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