Abstract
Cardiovascular mortality has been considered as the most important risk associated with chronic kidney disease. The mechanisms underlying this include inflammation, poor control of serum phosphate, high serum calcium, increased calcification of the arteries and cardiac valves, hyperlipidemia, diabetes, severe anemia, uric acid accumulation and others. Elevated phosphate levels have been strongly associated with increased mortality, thus phosphate-binding drugs have long been used to control the increase serum phosphate levels. However, phosphate-binding drugs differ considerably and recently numerous publications suggest differences between agents in the effects on overall mortality. The resin-based phosphate binders, comprising sevelamer and colestilan, not only reduce serum phosphate but also do not raise serum calcium. In addition, they reduce serum LDL-C, inflammation, uric acid and high Hba1c values. These differences suggest that not all phosphate binders may be equal in the context of cardiovascular mortality in this patient population.
Financial & competing interests disclosure
F Locatelli has been a member of an advisory board and/or speaker in meetings supported by Abbvie, Amgen, Fresenius Pharma, Keryx, Menarini, Mitsubishi Tanabe Pharma Corporation, Sanofi Aventis and Shire Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Chronic kidney disease is associated with much higher cardiovascular mortality rates than the non-chronic kidney disease population.
The mechanisms responsible may differ from the general population. High phosphorus/increased calcification exacerbated by localized inflammation may be leading contenders. Additional culprits being, involvement of high LDL-C and serum urate, both of which may exacerbate inflammation and other factors as in the general population, such as diabetes, severe anemia and high blood pressure etc.
The resin-based phosphate binders possess multiple actions that could benefit patients in terms of cardiovascular mortality.
The outcome data in this patient pool is suggesting a differential effect of non-calcium binders versus calcium binders.
Key issues remaining would include a better understanding of the relative efficacy of resin-based binders versus other agents, particularly relative effects versus calcium-based binders on vascular calcification and an understanding of the relative importance of high serum lipids versus serum phosphate/vascular calcification at various stages of chronic kidney disease.