Phosphate binder

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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.

Contents

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 the food we eat; 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 & 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).

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 BinderBrandsAdvantagesDisadvantages
Aluminum salts AlucapsCalcium freeRisk of aluminum toxicity
BasaljelHigh binder efficiency regardless of pHRequires frequent monitoring-extra cost
Cheap
Moderate tablet burden
Calcium carbonate CalcichewAluminum freeCalcium containing-potential risk of hypercalcemia and ectopic calcification
TitralacModerate binding efficacyParathyroid hormone oversuppression
Relatively low costGastrointestinal side effects
Moderate tablet burdenEfficacy pH dependent
Chewable
Calcium acetate Lenal AceAluminum freeCalcium containing-potential risk of hypercalcemia and ectopic calcification
PhosLoHigher efficacy than calcichew/sevelamerParathyroid hormone oversuppression
Moderately cheapGastrointestinal side effects
Lower calcium load than calcium carbonateLarge tablets & capsules, nonchewable formulation
Sevelamer hydrochloride/Sevelamer carbonate RenagelAluminium and calcium freeRelatively costly
RenvelaNo gastrointestinal absorptionHigh pill burden
Moderate efficacyLarge tablets, nonchewable formulation
Reduces total and low-density lipoprotein cholesterolGastrointestinal side effects
Binds fat-soluble vitamins
Lanthanum carbonate FosrenolAluminum and calcium freeRelatively costly
Minimal gastrointestinal absorptionGastrointestinal side effects
High efficacy across full pH rangeLarger tablet size may cause choking if not chewed well
Chewable formulation
Palatable
Low tablet burden
Ferric CitrateAuryxiaIron basedVery costly
Tablets can be toxic to young children
Stool discoloration - may turn them black, obscuring intestinal bleeding

Related Research Articles

<span class="mw-page-title-main">Parathyroid hormone</span> Mammalian protein found in Homo sapiens

Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

<span class="mw-page-title-main">Calcium metabolism</span> Movement and regulation of calcium ions in and out of the body

Calcium metabolism is the movement and regulation of calcium ions (Ca2+) in (via the gut) and out (via the gut and kidneys) of the body, and between body compartments: the blood plasma, the extracellular and intracellular fluids, and bone. Bone acts as a calcium storage center for deposits and withdrawals as needed by the blood via continual bone remodeling.

<span class="mw-page-title-main">Hypocalcemia</span> Low calcium levels in ones blood serum

Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L, while levels less than 2.1 mmol/L are defined as hypocalcemic. Mildly low levels that develop slowly often have no symptoms. Otherwise symptoms may include numbness, muscle spasms, seizures, confusion, or in extreme cases cardiac arrest.

Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemia. Those with a mild increase that has developed slowly typically have no symptoms. In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones or an abnormal heart rhythm including cardiac arrest.

<span class="mw-page-title-main">Hyperparathyroidism</span> Increase in parathyroid hormone levels in the blood

Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands or as response to external stimuli.

Tumor lysis syndrome (TLS) is a group of metabolic abnormalities that can occur as a complication from the treatment of cancer, where large amounts of tumor cells are killed off (lysed) from the treatment, releasing their contents into the bloodstream. This occurs most commonly after the treatment of lymphomas and leukemias and in particular when treating non-Hodgkin lymphoma, acute myeloid leukemia, and acute lymphoblastic leukemia. This is a potentially fatal complication and patients at increased risk for TLS should be closely monitored while receiving chemotherapy and should receive preventive measures and treatments as necessary. TLS can also occur on its own although this is less common.

<span class="mw-page-title-main">Electrolyte imbalance</span> Medical condition

Electrolyte imbalance, or water-electrolyte imbalance, is an abnormality in the concentration of electrolytes in the body. Electrolytes play a vital role in maintaining homeostasis in the body. They help to regulate heart and neurological function, fluid balance, oxygen delivery, acid–base balance and much more. Electrolyte imbalances can develop by consuming too little or too much electrolyte as well as excreting too little or too much electrolyte. Examples of electrolytes include calcium, chloride, magnesium, phosphate, potassium, and sodium.

Hypermagnesemia is an electrolyte disorder in which there is a high level of magnesium in the blood. Symptoms include weakness, confusion, decreased breathing rate, and decreased reflexes. Complications may include low blood pressure and cardiac arrest.

<span class="mw-page-title-main">Hyperphosphatemia</span> Medical condition

Hyperphosphatemia is an electrolyte disorder in which there is an elevated level of phosphate in the blood. Most people have no symptoms while others develop calcium deposits in the soft tissue. Often there is also low calcium levels which can result in muscle spasms.

Renal osteodystrophy is currently defined as an alteration of bone morphology in patients with chronic kidney disease (CKD). It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder (CKD-MBD). The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.

<span class="mw-page-title-main">Sevelamer</span> Chemical compound

Sevelamer (rINN) is a phosphate binding medication used to treat hyperphosphatemia in patients with chronic kidney disease. When taken with meals, it binds to dietary phosphate and prevents its absorption. Sevelamer was invented and developed by GelTex Pharmaceuticals. Sevelamer is marketed by Sanofi under the brand names Renagel and Renvela.

Lanthanum carbonate, La2(CO3)3, is the salt formed by lanthanum(III) cations and carbonate anions. It is an ore of lanthanum metal (bastnäsite), along with monazite.

<span class="mw-page-title-main">Secondary hyperparathyroidism</span> Medical condition

Secondary hyperparathyroidism is the medical condition of excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcemia, with resultant hyperplasia of these glands. This disorder is primarily seen in patients with chronic kidney failure. It is sometimes abbreviated "SHPT" in medical literature.

<span class="mw-page-title-main">Tertiary hyperparathyroidism</span> Medical condition

Tertiary hyperparathyroidism is a condition involving the overproduction of the hormone, parathyroid hormone, produced by the parathyroid glands. The parathyroid glands are involved in monitoring and regulating blood calcium levels and respond by either producing or ceasing to produce parathyroid hormone.

Phosphate nephropathy or nephrocalcinosis is an adverse renal condition that arises with a formation of phosphate crystals within the kidney's tubules. This renal insufficiency is associated with the use of oral sodium phosphate (OSP) such as C.B. Fleet's Phospho soda and Salix's Visocol, for bowel cleansing prior to a colonoscopy.   

<span class="mw-page-title-main">Milk-alkali syndrome</span> Medical condition

Milk-alkali syndrome (MAS), also referred to as calcium-alkali syndrome, is the third most common cause of hypercalcemia. Milk-alkali syndrome is characterized by elevated blood calcium levels, metabolic alkalosis, and acute kidney injury.

<span class="mw-page-title-main">Nephrocalcinosis</span> Medical condition caused by the deposition of calcium salts in the kidneys

Nephrocalcinosis, once known as Albright's calcinosis after Fuller Albright, is a term originally used to describe the deposition of poorly soluble calcium salts in the renal parenchyma due to hyperparathyroidism. The term nephrocalcinosis is used to describe the deposition of both calcium oxalate and calcium phosphate. It may cause acute kidney injury. It is now more commonly used to describe diffuse, fine, renal parenchymal calcification in radiology. It is caused by multiple different conditions and is determined by progressive kidney dysfunction. These outlines eventually come together to form a dense mass. During its early stages, nephrocalcinosis is visible on x-ray, and appears as a fine granular mottling over the renal outlines. It is most commonly seen as an incidental finding with medullary sponge kidney on an abdominal x-ray. It may be severe enough to cause renal tubular acidosis or even end stage kidney disease, due to disruption of the kidney tissue by the deposited calcium salts.

Familial hypocalciuric hypercalcemia (FHH) is an inherited condition that can cause hypercalcemia, a serum calcium level typically above 10.2 mg/dL; although uncommon. It is also known as familial benign hypocalciuric hypercalcemia (FBHH) where there is usually a family history of hypercalcemia which is mild, a urine calcium to creatinine ratio <0.01, and urine calcium <200 mg/day.

Calcium acetate/magnesium carbonate is a fixed-dose combination drug that contains 110 mg calcium and 60 mg magnesium ions and is indicated as a phosphate binder for dialysis patients with hyperphosphataemia. It is registered by Fresenius Medical Care under the trade names Renepho (Belgium) and OsvaRen.

Sucroferric oxyhydroxide, sold under the brand name Velphoro, is a non-calcium, iron-based phosphate binder used for the control of serum phosphorus levels in adults with chronic kidney disease (CKD) on haemodialysis (HD) or peritoneal dialysis (PD). It is used in form of chewable tablets.

References

  1. 1 2 3 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.
  2. 1 2 3 4 5 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.
  3. 1 2 3 4 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.
  4. 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.
  5. Burtis, C.A.; Ashwood, E.R. and Bruns, D.E. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th Edition. Elsevier. pp1552
  1. ^ Lederer E, Ouseph R, Erbeck K. Hyperphosphatemia, eMedicine.com, URL: Hyperphosphatemia: Practice Essentials, Background, Pathophysiology, Accessed on July 14, 2005.
  2. ^ 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.

Common Phosphate Binders