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Phosphate binders are medications used to reduce the absorption of dietary phosphate; they are taken along with meals and snacks. They are frequently used in people with chronic kidney failure (CKF), who are less able to excrete phosphate, resulting in an elevated serum phosphate.

Mechanism of action

These agents work by binding to phosphate in the GI tract, thereby making it unavailable to the body for absorption. Hence, these drugs are usually taken with meals to bind any phosphate that may be present in the ingested food. Phosphate binders may be simple molecular entities (such as magnesium, aluminium, calcium, or lanthanum salts) that react with phosphate and form an insoluble compound.

Calcium carbonate

Calcium-based phosphate binders, such as calcium carbonate, directly decrease phosphate levels by creating insoluble calcium–phosphate complexes which gets eliminated in the feces.^[1]

Lanthanum carbonate

Non-calcium-based phosphate binders, including lanthanum carbonate, form insoluble complexes with phosphates in food, thereby reducing the amount of phosphate in the body.^[1]

Sevelamer carbonate

Sevelamer is an insoluble polymeric amine, which is protonated once in the intestines and this allows it to bind dietary phosphate. Phosphates are eliminated along with sevelamer, leading to a decrease in the body's phosphate levels.^[1]

Medical use

For people with chronic kidney failure, controlling serum phosphate is important because it is associated with bone pathology and regulated together with serum calcium by the parathyroid hormone (PTH).^[1]

Adverse effects

Calcium carbonate

GI effects (nausea, vomiting, constipation)^[2]
Risk of cardiovascular calcification^[3]
Risk of hypercalcemia^[3]

Lanthanum carbonate

GI obstruction^[2]
Bile duct obstruction^[2]
Hepatic impairment^[2]
No hypercalcemia risk^[3]

Sevelamer carbonate

GI effects (nausea, vomiting, constipation, flatulence)^[2]
No hypercalcemia risk^[3]

Choice of agent

There have been limited trials comparing phosphate binders to placebo in the treatment of hyperphosphatemia in people with chronic kidney disease. When compared with people receiving calcium-based binders, people taking sevelamer have a reduced all-cause mortality.^[4]

Types

Summary of Common Oral Phosphate Binders^[5]
Phosphate Binder	Brands	Advantages	Disadvantages
Aluminum salts	Alucaps	Calcium free	Risk of aluminum toxicity
	Basaljel	High binder efficiency regardless of pH	Requires frequent monitoring-extra cost
		Cheap
		Moderate tablet burden
Calcium carbonate	Calcichew	Aluminum free	Calcium containing-potential risk of hypercalcemia and ectopic calcification
	Titralac	Moderate binding efficacy	Parathyroid hormone oversuppression
		Relatively low cost	Gastrointestinal side effects
		Moderate tablet burden	Efficacy pH dependent
		Chewable
Calcium acetate	Lenal Ace	Aluminum free	Calcium containing-potential risk of hypercalcemia and ectopic calcification
	PhosLo	Higher efficacy than calcichew/sevelamer	Parathyroid hormone oversuppression
		Moderately cheap	Gastrointestinal side effects
		Lower calcium load than calcium carbonate	Large tablets & capsules, nonchewable formulation
Sevelamer hydrochloride/Sevelamer carbonate	Renagel	Aluminium and calcium free	Relatively costly
	Renvela	No gastrointestinal absorption	High pill burden
		Moderate efficacy	Large tablets, nonchewable formulation
		Reduces total and low-density lipoprotein cholesterol	Gastrointestinal side effects
			Binds fat-soluble vitamins
Lanthanum carbonate	Fosrenol	Aluminum and calcium free	Relatively costly
		Minimal gastrointestinal absorption	Gastrointestinal side effects
		High efficacy across full pH range	Larger tablet size may cause choking if not chewed well
		Chewable formulation
		Palatable
		Low tablet burden
Ferric Citrate	Auryxia	Iron based	Very costly
			Tablets can be toxic to young children
			Stool discoloration - may turn them black, obscuring intestinal bleeding

Calcium acetate/magnesium carbonate

References

^ ^a ^b ^c Daoud, Kirollos; Anwar, Nihad; Nguyen, Timothy (2023). "The Role of Iron-Based Phosphate Binder in the Treatment of Hyperphosphatemia". Nephrology Nursing Journal. 50 (2): 140. doi:10.37526/1526-744x.2023.50.2.140. ISSN 1526-744X.
^ ^a ^b ^c ^d ^e Daoud, Kirollos; Anwar, Nihad; Nguyen, Timothy (2023). "The Role of Iron-Based Phosphate Binder in the Treatment of Hyperphosphatemia". Nephrology Nursing Journal. 50 (2): 140. doi:10.37526/1526-744x.2023.50.2.140. ISSN 1526-744X.
^ ^a ^b ^c ^d Jadav, Paresh R.; Husain, S. Ali; Mohan, Sumit; Crew, Russell (May 2022). "Non calcium phosphate binders - Is there any evidence of benefit". Current Opinion in Nephrology & Hypertension. 31 (3): 288–296. doi:10.1097/MNH.0000000000000796. ISSN 1062-4821 – via Ovid.
^ Patel, L; Bernard, LM; Elder, GJ (14 December 2015). "Sevelamer versus calcium-based binders for treatment of hyperphosphatemia in CKD: a meta-analysis of randomized controlled trials". Clinical Journal of the American Society of Nephrology. 11 (2): 232–244. doi:10.2215/CJN.06800615. PMC 4741042. PMID 26668024.
^ Burtis, C.A.; Ashwood, E.R. and Bruns, D.E. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th Edition. Elsevier. pp1552

^ Lederer E, Ouseph R, Erbeck K. Hyperphosphatemia, eMedicine.com, URL: Hyperphosphatemia: Practice Essentials, Background, Pathophysiology, Accessed on July 14, 2005.
^ Spiegel, David M.; Farmer, Beverly; Smits, Gerard; Chonchol, Michel (2007). "Magnesium Carbonate is an Effective Phosphate Binder for Chronic Hemodialysis Patients: A Pilot Study". Journal of Renal Nutrition. 17 (6): 416–22. doi:10.1053/j.jrn.2007.08.005. PMID 17971314.

External links

High Phosphate Control - Official Fosrenol Homepage
Phosphate Binders: What Are They And How Do They Work? - American Association of Kidney Patients*
Phosphate Binders - National Kidney Foundation
Phosphate Binders - Northwest Kidney Centers - a center that provides services for people with ESRD in the Seattle area.
High Phosphate - Phosphorus Control - Information for healthcare professionals on the treatment and management of hyperphosphatemia