Management of Hyperphosphatemia in Chronic Kidney Disease

Neenoo Khosla, Stuart M Sprague
US Nephrology, 2011;6(1):16-20
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Abstract

Early in the development of chronic kidney disease (CKD), most patients develop significant disorders in bone and mineral metabolism, which is referred to as chronic kidney disease-mineral bone disorder (CKD-MBD). Phosphate retention appears to be a central causal perturbation in the development of CKD-MBD. Furthermore, the role of phosphate in the development of vascular calcification and its association with an increased relative risk for death for those with various degrees of hyperphosphatemia in CKD is of particular concern. Treatment for patients with hyperphosphatemia includes dietary phosphate restriction, the use of phosphate binders, and/or increasing the frequency or duration of dialysis. However, phosphate binder therapy is the primary therapeutic intervention to control serum phosphate concentrations in patients with CKD. The ideal phosphate binder is one that is maximally effective in dietary phosphate binding, has minimal systemic absorption and adverse effects, and has a low cost and low pill burden. Over the years, the use of phosphate binder therapy has evolved in order to fulfill these goals with variable success. This review will survey the current landscape of the available phosphate binders as well as briefly discuss some emerging therapies.
Keywords
Hyperphosphatemia, phosphate binders, chronic kidney disease-mineral bone disorder, vascular calcification, phosphorous, sevelamer, lanthanum, calcium
Disclosure Stuart M Sprague, DO, FASN, FACP, has received research funding from Abbott, Shire, Mitsubishi, and Ineos, and has served as a consultant to Shire and Ineos. Neenoo Khosla has no conflicts of interest to declare.
Received: April 06, 2011 | Accepted May 26, 2011 | Citation US Nephrology, 2011;6(1):16-20
Correspondence: Stuart M Sprague, DO, FASN, FACP, Division of Nephrology and Hypertension, North Shore University HealthSystem, University of Chicago Pritzker School of Medicine, 2650 Ridge Avenue, Evanston, Illinois 60201. E: stuartmsprague@gmail.com

Phosphate is essential to signal transduction, cell membrane function, and energy exchange. The normal Western diet usually contains 1,000– 2,000 mg of phosphate daily and 60–80 % of this is absorbed into the gastrointestinal (GI) tract. The average adult maintains phosphate balance via renal excretion and the serum phosphate is a reflection of dietary absorption, renal excretion, net flux into and out of tissues, and intracellular stores.

The development of chronic kidney disease (CKD) is associated with decreased phosphate excretion, resulting in a positive phosphate balance. The compensatory mechanism to prevent phosphate accumulation includes decreases in calcitriol,1,2 as well as increases in parathyroid hormone (PTH)1,2 and fibroblast growth factor 23 (FGF-23).3 However, hyperphosphatemia does not occur until advanced CKD, usually late CKD stage 4 disease.1,2 The development of phosphate retention and hyperphosphatemia is central in the development of chronic kidney disease-mineral bone disorder (CKD-MBD).4

Of particular concern is the role of phosphate in the development of vascular calcification, a central feature in the high cardiovascular mortality associated with CKD.5,6 The important role of phosphate was highlighted by the numerous studies of patients with end-stage kidney disease (ESKD), which demonstrated the increased relative risk for death for those with various degrees of hyperphosphatemia (see Table 1).5–12

The recognition of pathophysiologic effects of hyperphosphatemia has resulted in several approaches to therapy; unfortunately no single approach has effectively controlled the problems associated with hyperphosphatemia. Treatment for patients with hyperphosphatemia includes dietary phosphate restriction, the use of phosphate binders, and/or increasing the frequency or duration of dialysis. Use of phosphate-restricted diets in combination with oral phosphate binders has become well established for the management of hyperphosphatemia in patients with CKD stages 3–5 and 5D. However, phosphate-restricted diets are of limited value as severe phosphate restriction would lead to protein malnutrition13 and diets would be generally unpalatable. The use of phosphate binders is associated with side effects, most commonly of GI origin. In dialysis patients, phosphate binders may account for up to 50 % of the high pill burden these patients have to deal with.14 Phosphate binder therapy has evolved to be the primary therapeutic intervention to control serum phosphate concentrations in patients with CKD.

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