An Update on Phosphate Binders: A Dietitian's Perspective
2016; Elsevier BV; Volume: 26; Issue: 4 Linguagem: Inglês
10.1053/j.jrn.2016.01.009
ISSN1532-8503
Autores Tópico(s)Pharmacological Effects and Toxicity Studies
ResumoControl of serum phosphorus (PO4) has been long recognized as a goal in the nutritional and medical management of the patients with chronic kidney disease. Phosphate-binding compounds were introduced in the 1970s for the treatment of hyperphosphatemia in patients on dialysis after it was observed that oral administration of aluminum hydroxide as an antacid also reduced serum PO4 levels. Forty years later, aluminum is very seldom used as a phosphate binder as many other safer compounds are now available. This article is a comprehensive review, geared to the renal dietitian, of the most common binder categories. It will discuss pharmacokinetics, side effects, initial and optimal doses, phosphate affinity, and controversies of use. It will also review two novel approaches to serum PO4 management in chronic kidney disease patients receiving dialysis and provide a new calculation by which binders can be compared. Control of serum phosphorus (PO4) has been long recognized as a goal in the nutritional and medical management of the patients with chronic kidney disease. Phosphate-binding compounds were introduced in the 1970s for the treatment of hyperphosphatemia in patients on dialysis after it was observed that oral administration of aluminum hydroxide as an antacid also reduced serum PO4 levels. Forty years later, aluminum is very seldom used as a phosphate binder as many other safer compounds are now available. This article is a comprehensive review, geared to the renal dietitian, of the most common binder categories. It will discuss pharmacokinetics, side effects, initial and optimal doses, phosphate affinity, and controversies of use. It will also review two novel approaches to serum PO4 management in chronic kidney disease patients receiving dialysis and provide a new calculation by which binders can be compared. Control of serum phosphorus (PO4) has been long recognized as a goal in the nutritional and medical management of the patients with chronic kidney disease (CKD). The negative sequelae of hyperphosphatemia in the CKD population have been well established.1Block G.A. Klassen P.S. Lazarus J.M. Ofsthun N. Lowrie E.G. Chertow G.M. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis.J Am Soc Nephrol. 2004; 15: 2208-2218Crossref PubMed Scopus (2213) Google Scholar, 2Qunibi W.Y. Nolan C.A. Ayus J.C. Cardiovascular calcification in patients with end-stage renal disease: a century-old phenomenon.Kidney Int Suppl. 2002; 62: S73-S80Abstract Full Text Full Text PDF Scopus (127) Google Scholar, 3Stevens L.A. Djurdjev O. Cardew S. Cameron E.C. Levin A. Calcium, phosphate, and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality: evidence for the complexity of the association between mineral metabolism and outcomes.J Am Soc Nephrol. 2004; 15: 770-779Crossref PubMed Scopus (314) Google Scholar, 4Jamal S.A. Vandermeer B. Raggi P. et al.Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis.Lancet. 2013; 382: 1268-1277Abstract Full Text Full Text PDF PubMed Scopus (348) Google Scholar Current therapies for management include providing renal replacement therapy, limiting dietary PO4, and prescribing phosphate-binding compounds. Management of serum PO4 is a primary responsibility of the renal dietitian by providing the dialysis patient with continual, ongoing education of dietary PO4 sources, and the use of phosphate binders. This education has become more challenging over the past decade as we have learned that the bioavailability of PO4 differs between organic and inorganic sources. The understanding of bioavailability challenges some of the previous education about which foods are highest in PO4. Another challenge is keeping up with the development and approval of new phosphate-binding compounds and identifying the most appropriate binder for individual patients. The number of Food and Drug Administration (FDA) approved phosphate-binding compounds continues to grow, each having advantages and disadvantages for use. The renal dietitian must understand the use, dosage, and adverse events of phosphate binders and navigate the world of medication insurance before making a binder recommendation. Phosphate-binding compounds were introduced in the 1970s for the treatment of hyperphosphatemia in patients on dialysis after it was observed that oral administration of aluminum hydroxide as an antacid also reduced serum PO4 levels.5Bailey R.R. Eastwood J.B. Clarkson E.M. et al.The effect of aluminium hydroxide on calcium, phosphorus and aluminium balances and the plasma parathyroid hormone in patients with chronic renal failure.Clin Sci. 1971; 41: 5P-6PCrossref Google Scholar Forty years later, aluminum is almost never used as a phosphate binder as many other safer compounds are now available. Calcium-based binders (calcium bicarbonate and calcium acetate) became the binder of choice in the 1980s and 1990s. They were effective and did not lead to the encephalopathy and bone disease seen with aluminum compounds; however, in more recent years, their use has been linked to the development of cardiac and metastatic calcification.4Jamal S.A. Vandermeer B. Raggi P. et al.Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis.Lancet. 2013; 382: 1268-1277Abstract Full Text Full Text PDF PubMed Scopus (348) Google Scholar, 6Chertow G.M. Burke S.K. Raggi P. Treat to Goal Working GroupSevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients.Kidney Int. 2002; 62: 245-252Abstract Full Text Full Text PDF PubMed Scopus (1331) Google Scholar, 7Block G.A. Spiegel D.M. Ehrlich J. et al.Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis.Kidney Int. 2005; 68: 1815-1824Abstract Full Text Full Text PDF PubMed Scopus (720) Google Scholar, 8Block G.A. Raggi P. Bellasi A. Kooienga L. Spiegel D.M. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.Kidney Int. 2007; 71: 438-441Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar, 9Spiegel D.M. Raggi P. Smits G. Block G.A. Factors associated with mortality in patients new to haemodialysis.Nephrol Dial Transplant. 2007; 22: 3568-3572Crossref PubMed Scopus (49) Google Scholar, 10Zhang Q. Li M. Lu Y. et al.Meta-analysis comparing sevelamer and calcium-based phosphate binders on cardiovascular calcification in hemodialysis patients.Nephron Clin Pract. 2010; 115: c259-c267Crossref PubMed Scopus (22) Google Scholar In 2001, the first nonmetal, nonabsorbable anion exchange binder, sevelamer hydrochloride (SH) was launched.11Genzyme Corporation. About Genzyme. Cambridge, MA. Available at: http://www.genzyme.com/Company/About-Genzyme.aspx Accessed April 1, 2015.Google Scholar, 12[email protected] Approved Drug Products Database. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm Accessed April 1, 2015.Google Scholar SH has the advantage of reducing a patient's exposure to calcium. However, in the ion exchange, hydrochloride (HCl) was released increasing a patient's acid load and contributing to metabolic acidosis. In 2004, lanthanum carbonate was launched as the first chewable non–calcium-based binder (now also available in powder form).12[email protected] Approved Drug Products Database. Available at: http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm Accessed April 1, 2015.Google Scholar, 13Fosrenol [Prescribing Information]. Shire US Inc., Wayne, PA2014Google Scholar Between 2007 and 2015, Phoslyra® (calcium acetate), the first prescription liquid-based binder, and Renvela® (sevelamer carbonate) became available.14Phoslyra [Prescribing Information]. Fresenius Medical Care North America, Waltham, MA2011Google Scholar, 15Renvela [Prescribing Information]. Genzyme Corporation, Cambridge, MA2009Google Scholar Bixalomer another nonmetal, nonabsorbable is available in Japan.16Akizawa T. Origasa H. Kameoka C. Kaneko Y. Kawasaki S. Bixalomer Study GroupRandomized controlled trial of bixalomer versus sevelamer hydrochloride in hemodialysis patients with hyperphosphatemia.Ther Apher Dial. 2014; 18: 122-131Crossref Scopus (29) Google Scholar, 17Akizawa T. Tsuruta Y. Okada Y. et al.Effect of chitosan chewing gum on reducing serum phosphorus in hemodialysis patients: a multi-center, randomized, double-blind, placebo-controlled trial.BMC Nephrol. 2014; 15: 98Crossref Scopus (9) Google Scholar Velphoro® (sucroferric oxyhydroxide), a chewable, iron-based binder with no significant change on iron parameters,18Velphoro [Prescribing Information]. Fresenius Medical Care North America, Waltham, MA2013Google Scholar and Auryxia® (ferric citrate) an iron-based binder with clinically and statistically significant increases in iron parameters.19Auryxia [Prescribing Information]. Keryx Biopharmaceuticals, New York, NY2014Google Scholar Additionally, studies have looked into once daily dosing of sevelamer, the use of niacin/nicotinamide, and the use of a salivary phosphate-binding chewing gum to improve serum PO4 levels.15Renvela [Prescribing Information]. Genzyme Corporation, Cambridge, MA2009Google Scholar, 20Cheng S.C. Young D.O. Huang Y. Delmez J.A. Coyne D.W. A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients.Clin J Am Soc Nephrol. 2008; 3: 1131-1138Crossref PubMed Scopus (87) Google Scholar, 21Block G.A. Persky M.S. Shamblin B.M. et al.Effect of salivary phosphate-binding chewing gum on serum phosphate in chronic kidney disease.Nephron Clin Pract. 2013; 123: 93-101Crossref Scopus (15) Google Scholar Table 1 shows the various FDA-approved compounds to demonstrate comparable efficacy.Table 1Comparison of Phosphate-Binding AgentsAgentCommon NameHow SuppliedStarting DoseEstimated PO4-Binding CapacityAdvantagesPotential Side Effects/DisadvantagesReferencesCalcium carbonateTums, Oscal, Calcichew, CaltrateVaries∼39 mg/gInexpensive, wide variety of products, easily available, no prescription requiredNot covered by insurance, hypercalcemia, hypoparathyroid, metastatic calcification, GI side effects, constipation6Chertow G.M. Burke S.K. Raggi P. Treat to Goal Working GroupSevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients.Kidney Int. 2002; 62: 245-252Abstract Full Text Full Text PDF PubMed Scopus (1331) Google Scholar, 8Block G.A. Raggi P. Bellasi A. Kooienga L. Spiegel D.M. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.Kidney Int. 2007; 71: 438-441Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar, 9Spiegel D.M. Raggi P. Smits G. Block G.A. Factors associated with mortality in patients new to haemodialysis.Nephrol Dial Transplant. 2007; 22: 3568-3572Crossref PubMed Scopus (49) Google Scholar, 27Savica V. Bellinghieri G. Monardo P. Muraca U. Santoro D. An update on calcium metabolism alterations and cardiovascular risk in patients with chronic kidney disease: questions, myths and facts.J Nephrol. 2013; 26: 456-464Crossref Scopus (15) Google ScholarCalcium acetatePhoslo PhoslyraTablet: 667 mg; Gelcap: 667 mg; Liquid: 667 mg per 5 mL2 tablets per meal; 2 gelcaps per meal; 10 mL per meal∼45 mg/gLess Ca absorption than calcium carbonateHypercalcemia, hypoparathyroid, metastatic calcification, GI side effects, constipation6Chertow G.M. Burke S.K. Raggi P. Treat to Goal Working GroupSevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients.Kidney Int. 2002; 62: 245-252Abstract Full Text Full Text PDF PubMed Scopus (1331) Google Scholar, 8Block G.A. Raggi P. Bellasi A. Kooienga L. Spiegel D.M. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.Kidney Int. 2007; 71: 438-441Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar, 9Spiegel D.M. Raggi P. Smits G. Block G.A. Factors associated with mortality in patients new to haemodialysis.Nephrol Dial Transplant. 2007; 22: 3568-3572Crossref PubMed Scopus (49) Google Scholar, 14Phoslyra [Prescribing Information]. Fresenius Medical Care North America, Waltham, MA2011Google Scholar, 27Savica V. Bellinghieri G. Monardo P. Muraca U. Santoro D. An update on calcium metabolism alterations and cardiovascular risk in patients with chronic kidney disease: questions, myths and facts.J Nephrol. 2013; 26: 456-464Crossref Scopus (15) Google ScholarSevelamer HClRenagelTablet: 400 mg, 800 mg; max dose: 13 g2-4 400 mg per meal; 1-2 800 mg per mealVaries ∼21 mg/gNoncalcium nonmetal binder, not absorbed, reduces serum lipid levelsContraindicated with pts who are at risk for small bowel obstruction, ↑S.Cl, ↓S.CO211Genzyme Corporation. About Genzyme. Cambridge, MA. Available at: http://www.genzyme.com/Company/About-Genzyme.aspx Accessed April 1, 2015.Google Scholar, 15Renvela [Prescribing Information]. Genzyme Corporation, Cambridge, MA2009Google Scholar, 24Daugirdas J.T. Finn W.F. Emmett M. Chertow G.M. Frequent Hemodialysis Network Trial GroupThe phosphate binder equivalent dose.Semin Dial. 2011; 24: 41-49Crossref PubMed Scopus (112) Google Scholar, 45Martin P. Wang P. Robinson A. et al.Comparison of dietary phosphate absorption after single doses of lanthanum carbonate and sevelamer carbonate in healthy volunteers: a balance study.Am J Kidney Dis. 2011; 57: 700-706Abstract Full Text Full Text PDF PubMed Scopus (36) Google ScholarSevelamer carbonateRenvelaTablet: 800 mg; Powder: 800 mg, 2,400 mg; max dose: 13 g1-2 per meal; 0.8-1.6 g per mealVaries ∼21 mg/gSame as aboveContraindicated with pts who are at risk for small bowel obstruction, ↑S.CO2. Not available worldwide11Genzyme Corporation. About Genzyme. Cambridge, MA. Available at: http://www.genzyme.com/Company/About-Genzyme.aspx Accessed April 1, 2015.Google Scholar, 15Renvela [Prescribing Information]. Genzyme Corporation, Cambridge, MA2009Google Scholar, 24Daugirdas J.T. Finn W.F. Emmett M. Chertow G.M. Frequent Hemodialysis Network Trial GroupThe phosphate binder equivalent dose.Semin Dial. 2011; 24: 41-49Crossref PubMed Scopus (112) Google Scholar, 45Martin P. Wang P. Robinson A. et al.Comparison of dietary phosphate absorption after single doses of lanthanum carbonate and sevelamer carbonate in healthy volunteers: a balance study.Am J Kidney Dis. 2011; 57: 700-706Abstract Full Text Full Text PDF PubMed Scopus (36) Google ScholarBixalomerKiklin (Japan)TabletNot knownNoncalcium, nonmetal, reduced GI effects than Renagel, no effect on S. Cl, ↑S.CO2.Less lipid lowering effects than Renagel. Not available worldwide.16Akizawa T. Origasa H. Kameoka C. Kaneko Y. Kawasaki S. Bixalomer Study GroupRandomized controlled trial of bixalomer versus sevelamer hydrochloride in hemodialysis patients with hyperphosphatemia.Ther Apher Dial. 2014; 18: 122-131Crossref Scopus (29) Google Scholar, 17Akizawa T. Tsuruta Y. Okada Y. et al.Effect of chitosan chewing gum on reducing serum phosphorus in hemodialysis patients: a multi-center, randomized, double-blind, placebo-controlled trial.BMC Nephrol. 2014; 15: 98Crossref Scopus (9) Google ScholarLanthanum carbonate (LaCO3)FosrenolChewable tablet: 500 mg, 750 mg, 1000 mg; Powder: 750 mg, 1000 mg500 mg per meal; max dose: 4500 mg/dayVaries on reference 135 mg/g, 45 mg/500 mgReduced pill burden, high binding capacity, noncalcium, crushableGI side effects may interfere with radiocontrast diagnostic results13Fosrenol [Prescribing Information]. Shire US Inc., Wayne, PA2014Google Scholar, 24Daugirdas J.T. Finn W.F. Emmett M. Chertow G.M. Frequent Hemodialysis Network Trial GroupThe phosphate binder equivalent dose.Semin Dial. 2011; 24: 41-49Crossref PubMed Scopus (112) Google Scholar, 29Chertow G.M. Martin K.J. Current and future therapies for the medical management of secondary hyperparathyroidism.Semin Dial. 1998; 11: 267-270Crossref Google ScholarSucroferric oxyhydroxideVelphoroChewable tablet: 500 mg500 mg per meal. Max dose: 3000 mg/day130 mg/tabReduced pill burden, noncalcium, crushableGI side effects18Velphoro [Prescribing Information]. Fresenius Medical Care North America, Waltham, MA2013Google Scholar, 25Daugirdas J.T. Chertow G.M. Larive B. et al.Effects of frequent hemodialysis on measures of CKD mineral and bone disorder.J Am Soc Nephrol. 2012; 23: 727-738Crossref PubMed Scopus (119) Google ScholarFerric citrateAuryxia Riona (Japan)Tablet: 1 g2 g per meal; max dose: 12 g/day46 mg/gramNoncalcium, increases iron parametersGI side effects, contraindicated with patients who have iron overload syndromes such as hemochromatosis19Auryxia [Prescribing Information]. Keryx Biopharmaceuticals, New York, NY2014Google Scholar, 30Daugirdas J.T. Blake P. Ing T. Bone disease.in: Wolters Kluwer Health. Philadelphia, PA Handbook of dialysis. 5th ed. Wolters Kluwer Health, Philadelphia, PA2015Google Scholar, 46Wilhelm M. Gaillard S. Rakov V. Funk F. The iron-based phosphate binder PA21 has potent phosphate binding capacity and minimal iron release across a physiological pH range in vitro.Clin Nephrol. 2014; 81: 251-258Crossref PubMed Scopus (40) Google Scholar, 51Van Buren P.N. Lewis J.B. Dwyer J.P. et al.The phosphate binder ferric citrate and mineral metabolism and inflammatory markers in maintenance dialysis patients: results from prespecified analyses of a randomized clinical trial.Am J Kidney Dis. 2015; 66: 479-488Abstract Full Text Full Text PDF PubMed Scopus (39) Google ScholarGI, gastrointestinal; HCl, hydrochloride. Open table in a new tab GI, gastrointestinal; HCl, hydrochloride. This article is a comprehensive review, geared to the renal dietitian, of the most common binder categories. It will discuss pharmacokinetics, side effects, initial and optimal doses, phosphate affinity, and controversies of use. It will also review two novel approaches to serum PO4 management in CKD patients receiving dialysis and provide a new calculation by which binders can be compared. Aluminum and magnesium-based binders are not included in this discussion. Aluminum is rarely used due to its toxic effects on the body, and little is known about the long-term safety and efficacy of magnesium-based binders. Additionally, patients taking magnesium-based binders are at risk for hypermagnesemia.22National Kidney FoundationK/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease.Am J Kidney Dis. 2003; 42: S1-S201Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar All phosphate-binding compounds work by reducing the absorption of dietary PO4 in the gastrointestinal (GI) tract. Compounds use the anionic nature of PO4 for ionic exchange with an active cation to form a nonabsorbable compound that is excreted in the feces.13Fosrenol [Prescribing Information]. Shire US Inc., Wayne, PA2014Google Scholar, 14Phoslyra [Prescribing Information]. Fresenius Medical Care North America, Waltham, MA2011Google Scholar, 15Renvela [Prescribing Information]. Genzyme Corporation, Cambridge, MA2009Google Scholar, 16Akizawa T. Origasa H. Kameoka C. Kaneko Y. Kawasaki S. Bixalomer Study GroupRandomized controlled trial of bixalomer versus sevelamer hydrochloride in hemodialysis patients with hyperphosphatemia.Ther Apher Dial. 2014; 18: 122-131Crossref Scopus (29) Google Scholar, 18Velphoro [Prescribing Information]. Fresenius Medical Care North America, Waltham, MA2013Google Scholar, 19Auryxia [Prescribing Information]. Keryx Biopharmaceuticals, New York, NY2014Google Scholar Calcium-, lanthanum-, and the newer iron-based salts exchange carbonate, acetate, oxyhydroxide, and citrate to bind with PO4. Sevelamer is a nonselective anion that will not only bind with PO4 but also binds with bile salts and other medications.15Renvela [Prescribing Information]. Genzyme Corporation, Cambridge, MA2009Google Scholar, 23Renagel [Prescribing Information]. 2014. Cambridge, MA 02142: Genzyme Inc.Google Scholar To obtain FDA approval for use in the United States, all binders have shown that they are effective in reducing serum PO4 levels in patients with CKD undergoing dialysis. Some companies compared effectiveness with placebo, and others used FDA-approved PO4-binding compounds to compare to current standard of care. Given the number of phosphate-binding agents, comparison between agents is challenging. Researchers in the Frequent Hemodialysis Network Trial faced this challenge when trying to interpret changes in serum PO4 levels. Their question was how much of the change was due to the increase in dialysis frequency and how much was due to the use of various phosphate binders? Daugirdas et al.24Daugirdas J.T. Finn W.F. Emmett M. Chertow G.M. Frequent Hemodialysis Network Trial GroupThe phosphate binder equivalent dose.Semin Dial. 2011; 24: 41-49Crossref PubMed Scopus (112) Google Scholar reviewed stool and urinary in vivo phosphate-binding capacities (PBC) in subjects with non-CKD and CKD. From here, they devised the “relative phosphate-binding coefficient” (RPBC) and the “phosphate binder equivalentdose” (PBED) to compare phosphate-binding capabilities in terms of milligrams of PO4 bound per gram of compound or per gram of active ingredient (lanthanum, sucroferric oxyhydroxide, and ferric citrate), arbitrarily choosing 1 g of calcium carbonate as the standard. Results from the Frequent Hemodialysis Network Trial suggest that patients with CKD and little urine output receiving conventional thrice weekly hemodialysis require approximately 6 g/day of a calcium carbonate to control serum PO4, and equivalent number of tablets required was established.24Daugirdas J.T. Finn W.F. Emmett M. Chertow G.M. Frequent Hemodialysis Network Trial GroupThe phosphate binder equivalent dose.Semin Dial. 2011; 24: 41-49Crossref PubMed Scopus (112) Google Scholar, 25Daugirdas J.T. Chertow G.M. Larive B. et al.Effects of frequent hemodialysis on measures of CKD mineral and bone disorder.J Am Soc Nephrol. 2012; 23: 727-738Crossref PubMed Scopus (119) Google Scholar Table 2 shows the RPBC, PBED, and the number of tablets required to reach the 6 g/day dose.Table 2Dosages of Selected Phosphorus Binders Required to Reach a Phosphorus Binder Equivalent Dose of 6.0 g/dayPhosphorus BinderUnit Dose Size (mg)Phosphate Binder Equivalent Dose of One Tablet to 1 g Ca CarbonateDose of Binder Needed to Reach a PBED of 6 g/dayApproximate Number of Tablets to Reach PBED of 6 g/dayg of Calcium in a 6 g PBED DoseCalcium carbonate7500.756.082.4Calcium acetate6670.676.091.5Osvaren (Mg carbonate + Ca acetate)435/235∗Each tablet contains 435 mg Mg carbonate and 235 mg Ca acetate.0.75—80.5Lanthanum500†Tablets are sold by weight of lanthanum and not of lanthanum carbonate.1.03.060Sevelamer carbonate8000.608.0100Sucroferric oxyhydroxide (Velphoro)5001.61.53.750Ferric citrate2100.642.090The equivalent dose of PA21 is based on a single randomized controlled trial versus sevelamer (Floege, 2014), and thus, the equivalent dose is not as precise as for some of the other binders, where multiple studies were considered. Ferric citrate numbers were obtained from a single clinical randomized controlled trial versus sevelamer and calcium acetate (Lewis et al. 2014); Osvaren is not available in the United States.Reproduced with permission from Wolter Kluwer.∗ Each tablet contains 435 mg Mg carbonate and 235 mg Ca acetate.† Tablets are sold by weight of lanthanum and not of lanthanum carbonate. Open table in a new tab The equivalent dose of PA21 is based on a single randomized controlled trial versus sevelamer (Floege, 2014), and thus, the equivalent dose is not as precise as for some of the other binders, where multiple studies were considered. Ferric citrate numbers were obtained from a single clinical randomized controlled trial versus sevelamer and calcium acetate (Lewis et al. 2014); Osvaren is not available in the United States. Reproduced with permission from Wolter Kluwer. The RPBC is a useful tool for practitioners switching between agents as a starting dose. Serum PO4 levels should be monitored, and dose titration was made per FDA package insert recommendations to reach optimal serum PO4 levels. For example, if a patient is prescribed six (6) 750-mg calcium carbonate tablets per day (4.5 g), the sevelamer equivalent dose would be ∼4 tablets per day.6tablets×750mg=4500mg(4.5grams)ofcalciumcarbonate4.5gramsofcalcium×0.75(sevelamerequivalentdose)=3.375gramsofsevelamer3375mgsevelamer÷800mg/tablet=4.2tablets Daugirdas et al. caution that the PBED is an estimate as the PBC studies showed an inverse relationship between PBC and binder dose. For example, urinary excretion studies using sevelamer revealed higher PBC with lower doses of sevelamer (1.6 gm/day sevelamer = 50 mg/g PBC) than with higher doses of sevelamer (7.5 gm/day sevelamer = 33 mg/g PBC), and urinary studies using lanthanum carbonate showed PBC of 96 mg/g with 1.93 g lanthanum versus 75 mg/g with 2.65 g lanthanum.24Daugirdas J.T. Finn W.F. Emmett M. Chertow G.M. Frequent Hemodialysis Network Trial GroupThe phosphate binder equivalent dose.Semin Dial. 2011; 24: 41-49Crossref PubMed Scopus (112) Google Scholar The estimated RPBC and PBED described for all phosphate binders provide tools practitioners can use to compare binders and determine initial phosphate binder prescriptions. Please note that on-label indications provide starting doses for each compound and are included in each section. Calcium-based–binding agents are the most commonly used medication for serum PO4 control despite multiple studies linking them to coronary and metastatic calcification.6Chertow G.M. Burke S.K. Raggi P. Treat to Goal Working GroupSevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients.Kidney Int. 2002; 62: 245-252Abstract Full Text Full Text PDF PubMed Scopus (1331) Google Scholar, 8Block G.A. Raggi P. Bellasi A. Kooienga L. Spiegel D.M. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.Kidney Int. 2007; 71: 438-441Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar, 9Spiegel D.M. Raggi P. Smits G. Block G.A. Factors associated with mortality in patients new to haemodialysis.Nephrol Dial Transplant. 2007; 22: 3568-3572Crossref PubMed Scopus (49) Google Scholar, 10Zhang Q. Li M. Lu Y. et al.Meta-analysis comparing sevelamer and calcium-based phosphate binders on cardiovascular calcification in hemodialysis patients.Nephron Clin Pract. 2010; 115: c259-c267Crossref PubMed Scopus (22) Google Scholar KDIGO and KDOQI guidelines recommend limiting or avoiding the use of calcium binders in patients who have elevated serum calcium levels, have low serum parathyroid levels, or have known calcification.22National Kidney FoundationK/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease.Am J Kidney Dis. 2003; 42: S1-S201Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar, 26Kidney Disease: Improving Global Outcomes (KDIGO) CKD–MBD Work GroupKDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).Kidney Int. 2009; 79: S1-S130Google Scholar Some studies have shown that many patients have calcification before dialysis is initiated calling into question the use calcium-based binders even in earlier stages of CKD.27Savica V. Bellinghieri G. Monardo P. Muraca U. Santoro D. An update on calcium metabolism alterations and cardiovascular risk in patients with chronic kidney disease: questions, myths and facts.J Nephrol. 2013; 26: 456-464Crossref Scopus (15) Google Scholar, 28Spiegel D.M. Block G.A. Should we be using calcium-containing phosphate binders in patients on dialysis?.Nat Clin Pract Nephrol. 2008; 4: 118-119Crossref PubMed Scopus (7) Google Scholar Despite the research, practitioners continue to use calcium-based binders to control serum PO4 and for its ability to lower parathyroid.29Chertow G.M. Martin K.J. Current and future therapies for the medical management of secondary hyperparathyroidism.Semin Dial. 1998; 11: 267-270Crossref Google Scholar Calcium carbonate is available over-the-counter without a prescription and is inexpensive. Various strengths are available; therefore, it is important to review with the patient the appropriate strength to use because approximately 20% to 30% of the elemental calcium will be absorbed.30Daugirdas J.T. Blake P. Ing T. Bone disease.in: Wolters Kluwer Health. Philadelphia, PA Handbook of dialysis. 5th ed. Wolters Kluwer Health, Philadelphia, PA2015Google Scholar There are multiple studies comparing the effectiveness of calcium carbonate with calcium acetate as a phosphate binder.31Pflanz S. Henderson I.S. McElduff N. Jones M.C. Calcium acetate versus calcium carbonate as phosphate-binding agents in chronic haemodialysis.Nephrol Dial Transplant. 1994; 9: 1121-1124PubMed Google Scholar, 32Choy B.Y. Lo W.K. Cheng I.K.P. Effectiveness of calcium acetate as a phosphate binder in patients undergoing continuous ambulatory peritoneal dialysis.Hong Kong Med J. 1998; 4: 23-26Google Scholar, 33Saif I. Halim A. Altaf A. et al.Comparison of calcium acetate with calcium carbonate as phosphate binder in patients on maintenance haemodialysis.J Ayub Med Coll Abbottabad. 2007; 19: 26-28Google Scholar
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