Magnesium salts, such as magnesium hydroxide and magnesium carbonate, can bind dietary phosphorus but are considered less effective than calcium salts. Thus, large doses are often required, and these may result in significant hypermagnesemia, diarrhea, and hyperkalemia. Hypermagnesemia can be prevented by reducing or eliminating magnesium from the dialysate.
An alternative approach is to use a combination of magnesium carbonate and calcium carbonate or magnesium carbonate and calcium acetate, as proposed by Spiegel and colleagues at the 2006 NKF Clinical Spring Meeting (abstract no. 152; available at download.journals.elsevierhealth.com/pdfs/journals/0272-6386/PIIS0272638606002605.pdf, accessed May 21, 2009). These compounds have been used as phosphate binders in the United States and in Europe.
A third combination is magnesium iron hydroxycarbonate (Alpharen; Ineos Healthcare), which contains magnesium and ferric iron.
A phase 2 study in hemodialysis patients showed that almost 50% of the patients taking Alpharen 3 g/day and most patients taking 6 g/day achieved the KDOQI target serum phosphate level, according to a report by McIntyre and colleagues presented at the American Society of Neprhology’s 2006 Renal Week (abstract no. F-PO108; available at www.asn-online.org/education_and_meetings/renal_week/archives/2006-abstracts-archive.pdf, accessed May 21, 2009).
There were no significant differences compared with pre-study standard treatment using either calcium carbonate or sevelamer. The GI effects of Alpharen 3 g/day did not differ significantly from placebo. However, about half of the patients on the 6-g/day dosage withdrew from the study mainly because of GI intolerance.
Nicotinic acid derivatives
Phosphorus transport through the apical membrane of small intestinal epithelial cells is coupled with sodium. Type IIb sodium-dependent phosphate co-transporter is a plasma membrane-bound symporter that mediates the movement into cells of extracellular phosphorus coupled with sodium ions.
A novel approach to controlling intestinal absorption of dietary phosphorus is to inhibit this intestinal co-transporter with nicotinic acid derivatives, such as nicotinamide, MCI-196, or niceritrol. Nicotinamide was found to decrease the transport of phosphorus by reducing the activity of sodium phosphate co-transporter in rodents (Nephrol Dial Transplant. 2005;20:1378-1384). Moreover, nicotinamide has shown some efficacy in a small preliminary human study in Japan (Kidney Int. 2004;65:1099-1104).
Phosphorus may be secreted in the saliva, which when swallowed contributes to hyperphosphatemia. Adding a salivary phosphate binder such as the natural polymer chitosan as a chewing gum may improve treatment of hyperphosphatemia in dialysis patients (J Am Soc Nephrol. 2009;20:639-644). Chitosan is a natural polymer derived from chitin, a polysaccharide found in the exoskeleton of shellfish, such as shrimp, lobster, and crabs, and used in water-purification plants.
Untreated hyperphosphatemia independently increases the risk of mortality in dialysis patients. Evidence suggests that treatment with currently available phosphate binders is suboptimal.
Consequently, there is need for new agents that address some of the challenges associated with current binder therapy. These newer phosphate binders are being evaluated and, when approved, will give our patients a wider range of products to choose from for more effective control of hyperphosphatemia.
Dr. Qunibi is Professor of Medicine and Medical Director of Dialysis Services at the University of Texas Health Sciences Center at San Antonio.