Evaluation of morbidity and mortality data related to cardiovascular calcification from calcium-containing phosphate binder use in patients undergoing hemodialysis

Abstract

Cardiovascular disease is the leading cause of death among patients with stage 5 chronic kidney disease. Several mechanisms are thought to contribute to vascular calcification and subsequent cardiovascular disease in patients who require hemodialysis. One of these mechanisms is the use of calcium-containing phosphate binders to treat hyperphosphatemia. Although most phosphate binding occurs in the gastrointestinal tract, some calcium is inevitably absorbed and has the potential to perpetuate the calcium-phosphorus product and the development of vascular and soft tissue calcification. Some phosphate binders such as sevelamer hydrochloride do not contain calcium and therefore may not carry the same risks. We examined the cardiovascular calcification effect and morbidity and mortality data with calcium-containing phosphate binders compared with sevelamer hydrochloride when given to patients with stage 5 chronic kidney disease for the treatment of hyperphosphatemia. A literature search using the MEDLINE and PubMed databases identified relevant articles from 1989-2009; nine studies compared vascular calcification between a calcium-containing phosphate binder and sevelamer hydrochloride. Three mortality studies were also identified. Seven of the nine studies reported a statistically significant increase in vascular calcification in patients taking calcium-containing phosphate binders as measured by coronary artery calcification scores and aortic calcification scores. In two trials, lower mortality rates were observed in the patients receiving sevelamer hydrochloride compared with calcium-containing phosphate binders. No significant difference in the mortality rate was observed in the third trial. Based on the current literature, it appears that calcium-containing phosphate binders promote the progression of vascular calcification to a greater extent than does sevelamer hydrochloride. In addition, some evidence suggests that sevelamer hydrochloride may reduce all-cause mortality rates in patients undergoing hemodialysis, particularly those aged 65 years or older. Thus, although sevelamer hydrochloride appears to be the more appropriate choice of phosphate binder for patients undergoing hemodialysis in whom cardiovascular calcification is a concern, more clinical trials are needed to further guide practitioners on the selection of phosphate binders.