Treatment Options in the Management of Phosphate Retention*

Hyperphosphatemia is an independent risk factor for mortality and cardiovascular events in patients with chronic kidney disease (CKD). For patients who cannot control their serum phosphate levels adequately with diet, agents that limit gastrointestinal phosphate uptake are indicated. The use of phosphate-binding agents has changed over the years as more is learned about the mechanisms that underlie the clinical effects of hyperphosphatemia and pharmacologic effects of the agents themselves. Calcium-containing oral agents largely replaced aluminum-based products because the latter, although effective, were associated with serious toxicities. A growing body of evidence suggests that calcium-based phosphate binders may increase the calcium load in patients with CKD, accelerating arterial calcification and increasing cardiovascular risk. Sevelamer hydrochloride and lanthanum carbonate are non–calcium-containing phosphate binders currently available for the management of hyperphosphatemia. In addition, several new therapeutic approaches are emerging as the understanding of vascular calcification evolves. (Adv Stud Med. 2007;7(5):146-151) H yperphosphatemia is associated with a range of complications in patients with chronic kidney disease (CKD), such as hyperparathyroidism, osteodystrophy, anemia, and soft-tissue calcification. The need for effective management of serum phosphate levels in end-stage renal disease (ESRD) has long been recognized as a treatment priority, and various management strategies have been used over the years. When controlling phosphate intake by dietary restriction and dialysis are not sufficient, binders that reduce intestinal absorption of phosphate are the mainstay of treatment to control high serum phosphorus. Aluminum-based agents were among the first phosphate-binding agents used. Although they were effective in reducing serum phosphate levels, they also were associated with serious toxicities. Calcium-containing oral preparations replaced the aluminum-based binders and have been used extensively since the late 1980s and early 1990s. However, recent evidence suggests that calciumbinding agents, by contributing an excess calcium load, may exacerbate vascular calcification. As discussed in the article by Drs Middleton and Malluche earlier in this monograph, both hyperphosphatemia and vascular calcification are associated with increased risk of cardiovascular mortality in patients with ESRD. Thus, alternatives to calcium-containing preparations may be important to reducing the cardiovascular risk in this vulnerable population. Sevelamer hydrochloride and lanthanum carbonate are calciumand aluminum-free agents with proven efficacy in the reduction of serum phosphate levels. Preliminary evidence indicates that these agents are not associated with increased vascular calcification. This paper will compare the safety, efficacy, and tolerability profiles of calcium binders, sevelamer, and lanthanum. Data regarding rates of arterial calcification in patients using these agents will be discussed in the PROCEEDINGS