Phosphorus reabsorption is primarily regulated by parathyroid hormone. A theoretical, in vitro, and in vivo study, Calcium acetate, an effective phosphorus binder in patients with renal failure, Calcium acetate control of serum phosphorus in hemodialysis patients, Long‐term (6 months) cross‐over comparison of calcium acetate with calcium carbonate as phosphate binder, Calcium acetate as a phosphorus binder in hemodialysis patients, Calcium acetate versus calcium carbonate as phosphate binders in hemodialysis patients, The treatment of uraemic hyperphosphataemia with calcium acetate and calcium carbonate: a comparative study, Control of predialytic hyperphosphatemia by oral calcium acetate and calcium carbonate. As a result, phosphorus binding can be achieved with a lower dose of calcium. Ideally, the best phosphorus binder would be inexpensive, nontoxic, well tolerated, and potent. Although calcium salt binders are efficacious and cost effective, long‐term safety questions about their use arose because of concern about excess calcium absorption, positive calcium balance, hypercalcemia, and their possible relationship to the development of soft‐tissue and cardiovascular calcifications. Mechanism of action. Therefore, phosphorus control with calcium acetate would be more likely to fall within the K‐DOQI calcium restriction guidelines. ).25, Effect of ingestion of calcium carbonate or calcium acetate on absorption of ingested phosphorus and calcium by hemodialysis patients (n = 6). The following sections highlight the differences between these 2 salts. 6 This is primarily because emerging evidence suggests calcium-based binders may accelerate vascular calcification and cardiovascular mortality. Calcium acetate, also called PhosLo, is one commonly used phosphorus binder. Serum calcium increased 9% during the study mostly in the first month of the study. The release of calcium from the skeleton, skeletal buffering of exogenous calcium, bone turnover rate, PTH status, and vitamin D activity are some of the many factors that affect the concentration of blood calcium independently of net calcium balance. Depending on the presence or absence of calcium in their molecular structure, phosphate binders can be classified as calcium-based and calcium-free. Their mechanism of action is based on the binding of dietary phosphate within the gastrointestinal lumen to prevent its absorption. The first is the era of alkaline aluminum salts. In addition, active transcellular phosphorus transport, which is regulated by vitamin D, becomes important when phosphorus intake is low.12 Unabsorbed phosphorus is excreted in the stool and, in healthy adults, the absorbed load of phosphorus is quantitively excreted into the urine. human milk from It can be used in combination with other calcium- and non-calcium-based phosphate binders and active vitamin D sterols. 22 In addition, they can result in over-suppression of parathyroid hormone and the development of adynamic bone. Use the link below to share a full-text version of this article with your friends and colleagues. gradually to reduce blood phosphate levels below 6 mg/dl without causing 58 Furthermore, there is some evidence that sevelamer hydrochloride can attenuate coronary and aortic calcification compared with calcium-based phosphate binders. Calcium citrate is a particularly poor phosphorus binder because the citrate anion competes with phosphorus to bind calcium26 (this is the property of citrate that makes it a critical urinary component for maintaining calcium solubility and reducing the risk of calcium stone formation). 59 Despite these advantages, gastrointestinal disturbances, … hypercalcemia. (2) Does ingestion of large amounts of calcium salts and the resultant positive calcium balance generate cardiovascular disease, or is it a marker for uncontrolled hyperphosphatemia? Phosphorus binders help to pass excess phosphorus out of the body in the stool, reducing the amount of phosphorus that … Critics of these studies (and proponents of calcium-based binders) argue that arterial calcification has not been shown to be associated with mortality in patients with ESRD. They also showed that proportional dietary phosphorus restriction could ameliorate much of this pathologic response. in vivo The aim of the present review is not to illustrate the specific actions produced by calcium-based binders and other drugs, including calcimimetic agents, but rather to focus on the direct and indirect mechanism of action of non-calcium phosphate binders. The results of multiple large long‐term studies of HD patients have confirmed that the dose of elemental calcium, in the form of calcium acetate, required to control serum phosphorus is about half the dose required when calcium carbonate is used.28-33 An important unresolved question is whether this translates to half as much (or even less) calcium absorption. This is where phosphorus binders come in. Administration of calcium acetate (50 mEq of calcium) with a meal (or just before or after—not shown) resulted in significantly greater phosphorus binding and less calcium absorption compared with that with administration of calcium acetate during fasting, n = 6 healthy normal subjects (adapted from Schiller et al.).56. The drug interaction of Phoslo® is characterized by the potential of calcium to bind to drugs with anionic functions (e.g., carboxyl and hydroxyl groups). 20 The usual effective dose is 2 to 8 g/day, given in divided doses with meals and with large snacks. With calcium acetate, more calcium was bound to phosphorus, so less calcium was available for absorption. The NKF/K‐DOQI guidelines state that the total dose of elemental calcium provided by calcium‐based phosphate binders should not exceed 1,500 mg/day. Thirty-two percent of patients received phosphate binders during treatment with BALVERSA ®. The pH of the gastrointestinal tract affects both the rate of dissolution of calcium salts and the subsequent binding reaction of the ionized calcium with phosphorus. Representation of systemic action of vitamin K on bone and vasculature in the calcium presence. Absorption. Tums is a form of calcium carbonate, which can also be effective. non-calcium based phosphate binders are thought to reduce cardiovascular mortality in patients with CKD compared to calcium acetate. The acidic conditions required for dissolution impair binding; conversely, at an alkaline pH, which is optimal for binding, the salt will not dissolve. Currently, calcium‐based binders are generally considered first‐line agents for the treatment of hyperphosphatemia in ESRD. 23,26. ... Avoid the use of calcium supplements, including calcium-based nonprescription antacids, concurrently with calcium acetate. Phosphate binder: Binds with dietary phosphate to form insoluble calcium phosphate, which is excreted in feces. This review focuses on calcium binders. When administering an oral medication with Phoslo® where a reduction in the bioavailability of that medication would have a clinica… These agents work by binding to phosphate in the GI tract, thereby making it unavailable to the body for absorption. Electrolyte . This drug activates calcium‐sensing receptors and has a number of effects including major inhibition of PTH secretion. Calcium carbonate. Calcium acetate may be used safely in pregnant women if calcium levels are Phosphate binders can be either calcium-containing compounds or calcium-free compounds, depending on the calcium content in their composition. Shortening of the myocardial action potential leads to decreased QT interval. In contrast, calcium acetate, a much more soluble salt (10,000 times more soluble than calcium carbonate), dissolves readily across the entire pH range. home/digestion health center/digestion a-z list/calcium acetate-oral article. Phosphate binder therapy has recently entered its third era, characterized by the introduction of several novel agents such as lanthanum carbonate (Fosrenol, Shire Pharmaceuticals) and the nonmetallic phosphorus binder sevelamer (Renagel, Genzyme Corporation). Iron arrested further calcification when added on days 7–15 in the presence of high Pi (1.30 ± 0.03 vs 0.61 ± 0.02; OD/mg protein; day 15; Pi vs Pi + Fe, The only reason such salts should be administered at night or when fasting would be that rare situation when a calcium load needs to be administered via the enteral route to a patient with chronic kidney disease. Calcium-based phosphate binders are the most commonly used phosphate binders in developing countries for their relatively low costs. Calcium-containing compounds (calcium carbonate, calcium acetate) have proven to be … Mechanism of Action The calcium-sensing receptor on the surface of the chief cell of the parathyroid gland is the principal regulator of PTH synthesis and secretion. Calcium acetate/magnesium carbonate; Mechanism of action. In all patients, restrict phosphate intake to 600-800 mg daily. The full text of this article hosted at iucr.org is unavailable due to technical difficulties. Hyperphosphatemia in patients with end‐stage renal disease (ESRD) is associated with secondary hyperparathyroidism and renal osteodystrophy, and is independently associated with an increased risk of mortality. while taking calcium acetate. The first effective calcium salt binder was calcium carbonate. Phoslo® may decrease the bioavailability of tetracyclines or fluoroquinolones via this mechanism. Calcium phosphate binders such as calcium carbonate or … Drug Name Confusion: Preventing Medication Errors, Calcium acetate helps reduce phosphate levels in Calcium acetate is a phosphate binder. Drug: Calcium-based phosphate binder Other Names: Calcium carbonate; Calcium acetate; Outcome Measures. Therefore, tight control of serum phosphorus is considered essential in these patients. Learn about our remote access options, Department of Internal Medicine, Baylor University Medical Center, Dallas, Texas. The possibility that long-term treatment could cause such side effects as metastatic calcification will require further investigation. Furthermore, recent research indicates an important role for other “phosphatonin” hormones such as fibroblast growth factor‐23.13 Adults with normal renal function are generally in zero or slightly negative phosphorus balance. Sevelamer is available as 400- and 800-mg tablets. Go to Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information. Therefore, … There are no empirical data on avoiding drug interactions between calcium acetate or Phoslo® and most concomitant drugs. One hour of in vitro phosphorus binding of calcium acetate approximated the theoretical binding capacity, whereas calcium carbonate binding of phosphorus was very poor (adapted from Sheikh et al.).25. Approximately 70% of patients in the Sensipar arm and 80% of the patients in the placebo arm completed the 6-month studies. Aluminum has potentially serious toxic risks. After 1 hour, calcium acetate had achieved virtual theoretical maximal phosphorus binding at any pH. monitored and kept within normal limits. The purpose of this review is to highlight the major differences among different calcium salts, the most commonly used class of phosphate binders. An overdose of calcium acetate may lead to progressive hypercalcemia, which may require emergency measures. A significant risk factor for cardiovascular disease in patients with ESRD is accelerated vascular calcification [2,3]. Calcium acetate should be stored at room temperature, 15 C to 30 C 241 We studied the effect of iron citrate (iron) on the progression of calcification in high-phosphate (Pi) calcified VSMC. More recently, major concern has been raised about excessive positive calcium balance and the possibility that this contributes to cardiovascular calcification, morbidity, and mortality. Dialysis removes a significant quantity of phosphorus, with a 4‐hour HD treatment removing about 1,000 mg of phosphorus.17 As most patients undergo HD 3 times a week, an estimated 3,000 mg of phosphorus is removed a week, an amount well short of the 5,000–6,000 mg of phosphorous a week that most adults absorb.17,18 Most HD and peritoneal dialysis patients remain hyperphosphatemic unless phosphate binders are used.19 However, longer, more frequent, or nocturnal HD sessions will remove additional phosphorus and may effectively control serum phosphorus.20. Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Absorption: 30-40%; however it is the unabsorbed drug that binds and removes phosphate. Ca = elemental calcium Liquid: calcium lactogluconate syrup: 20 mg ++ Ca /mL Tablets: Chewable (Tums 500 mg Ca ++ carbonate): 200 mg Ca Chewable (Tums Extra Strength 750 mg Ca ++ carbonate): 300 mg Ca Effervescent (Calcium Sandoz ++ Forte): 500 mg Ca Tablet (Oscal, Apo-cal 1250 mg Ca … Aluminium-based phosphate binders were followed by calcium salts (carbonate and acetate), which are the first-line intestinal phosphate binders, for reasons of cost, as well as for their beneficial action on a possible correction of mild hypocalcaemia. sepsis, medications, Not only should half as much calcium be required to provide equal phosphorus binding, but also an even smaller fraction of this smaller load should be absorbed compared with what would occur with calcium carbonate (because more calcium is used to bind phosphorus and therefore unavailable for absorption). (59 F to 86 F). However, compensating mechanisms fail when kidney dysfunction advances, resulting in positive phosphorus balance, which leads to progressive hyperphosphatemia.8,9,14. It works to bind phosphate in the digestive tract. phosphate binders, calcium-based binders are most effective when taken with meals (which also limits calcium absorption) ... Phosphate binders Mechanism of action Form, strength Initial dose Maximum recommended dose Cost per tablet Advantages Disadvantages Aluminium hydroxide Forms insoluble phosphate complexes in the gut 600 mg tablets 1 tablet 3 times a day with meals 2 tablets 3 times a … Fluoride ions promote the formation of fluorapatite in enamel in the presence of calcium and phosphate ions produced during enamel demineralization by plaque bacterial organic acids. Types. Chelates phosphate (& other anions, eg, oxalate) in intestine to form insoluble calcium phosphate, which is excreted in feces. Generic Drugs, Are They as Good as Brand-Names? Recently, iron-based phosphate binders have been proposed in advanced CKD to treat hyperphosphatemia. Aluminum bound virtually all the phosphorus regardless of pH, whereas optimal calcium binding required a pH > 5 (initial concentrations: phosphorous 320 mg/600 mL; calcium or aluminum 75 mEq/600 mL; adapted from Sheikh et al.).25. Calcium-based phosphorus binders have largely replaced aluminum-based binders and may also serve as calcium supplements. Calcium-based phosphate binders are the mainstay of phosphate-lowering therapy in CKD stage 4. If it were possible to accomplish, restriction of dietary phosphorus (in proportion to the reduction in kidney function) could largely prevent hyperphosphatemia. calcium acetate in December 1990. Bone turnover rate may have a greater impact on the development of hypercalcemia in dialysis patients than the dose of calcium salt.39, Vitamin D analogues, used to suppress parathyroid hormone secretion, have a major impact on serum calcium concentration and frequency of hypercalcemia. There is no theoretical reason that smaller doses of multiple agents would not prove to be the best approach. Calcium acetate may decrease the absorption of The results of these studies, and their limitations, are described in the next section. The prevention and the treatment of hyperphosphatemia is today far to be satisfactory. Which drugs or supplements interact with calcium acetate? However, dietary restriction alone is generally unsuccessful because phosphorus is such a ubiquitous component of most foodstuffs, and proteins are especially rich in phosphorus.15 This makes it virtually impossible to provide a nutritious and palatable diet and simultaneously markedly restrict phosphorus. Phosphorus binders (also called phosphate binders) prevent the body from absorbing the phosphorus from the food you eat. patients is 2 tablets or capsules with each meal. Pharmacokinetics. Bioavailability: 25-35%; food increases absorption 10-30%; antacid action dependent on gastric emptying time. Calcium-based binders (acetate and carbonate) bind phosphate ionically and are effective 21 and inexpensive, but their administration results in hypercalcemia in up to 50% of patients, especially when co-administered with vitamin D analogs. Patients with chronic kidney disease are often hypo‐ or achlorhydric as a result of gastritis and/or the frequent use of H2 receptor blockers or proton pump inhibitors.34 In theory, this could adversely affect the dissolution and efficacy of calcium carbonate. Kidney Int. Other calcium salts, including calcium citrate (Citracal, Mission Pharmaceuticals), calcium lactate, calcium gluconate and calcium salts of essential keto acid analogues, have been investigated as potential phosphorus binders.45-50 It has been shown that none of these has any advantage over calcium carbonate or acetate. Monitor the following parameters within 3 months after initiation of therapy or after dose adjustment, … The average serum calcium concentration and the frequency of hypercalcemia can be reduced by lowering the dialysate calcium concentration.42,43 Another advance likely to have a major impact in this arena is the calcimimetic drug cincalcet HCl (Sensipar, Amgen). Kidney Int. Secondary hyperparathyroidism is a frequently encountered problem in the management of patients with chronic kidney disease (CKD). 2 This is now believed to be the major mechanism of fluoride ion’s action in preventing enamel demineralization. 23 They have been … using calcium acetate. CKD affects about 1 in 9 adults, and about 300,000 patients with end‐stage renal disease (ESRD) in the United States require chronic dialysis therapy.1 The mortality rate among U.S. dialysis patients approaches 20% annually, with cardiovascular disease the single most important cause of death.2 The risk of cardiovascular mortality is especially great among young dialysis patients, exceeding that of age‐matched controls by more than 100‐fold.3. Calcium acetate more readily permits optimal phosphorus binding within these guidelines. Nonetheless, an extending range of phosphate binders are now available. Nonetheless, the available evidence indicates that calcium acetate is probably a more efficient calcium salt binder and may generate a lower calcium balance. Calcium based phosphate binders are known to reduce the levels of adsorbed phosphate by directly coupling reaction in the gastro-intestinal tract. Some of the renal causes of kidney failure include Treatment with the phosphate binder was discontinued for patients from the open-label study, and those patients whose serum phosphorus exceeded 5.5 mg/dL were eligible for entry into a double-blind, placebo-controlled, cross-over study. Bioavailability: 25-35%; food increases absorption 10-30%; antacid action dependent on gastric emptying time. Most patients require 3-4 tablets or capsules with each meal. The most important advantage of calcium acetate in comparison with calcium carbonate is that it binds equal amounts of phosphorus with a dose of elemental calcium only one half as large as that required for calcium carborare. Recognition of aluminum toxicity ushered in the second phosphate binder era, when calcium salts replaced alkaline aluminum salt binders. It also has become increasingly apparent that hyperphosphatemia plays a major role in the high morbidity and mortality associated with kidney dysfunction and failure.4-6 The association of hyperphosphatemia and kidney dysfunction has been known for more than 80 years,7 but the clinical impact and toxicity of hyperphosphatemia was not well recognized or understood until the early 1970s.8,9 At that time, Bricker et al.8,9 delineated the pathophysiologic cascade triggered by hyperphosphatemia.