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Concordance, a collaborative planning of treatment regimens fitting patients’ lives, is an under-recognized aspect of sustainable phosphate control. This article describes one academic dialysis center’s patient education intervention, various dosing methods of sevelamer carbonate powder, improved adherence patterns, and phosphate control results.

Pathology and consequences of CKD-MBD

Chronic kidney disease-mineral and bone disorder (CKD-MBD) contributes importantly to cardiovascular and mortality risk for patients with CKD and end-stage renal disease (ESRD).1 Frank hyperphosphatemia is a direct source of cardiovascular risk.2, 3 However, CKD-MBD pathology begins much earlier with the endocrine tradeoffs required to maintain phosphate excretion with decreasing nephron numbers; secondary hyperparathyroidism and increased fibroblast growth factor (FGF)-23 may exert physiologic consequences even while serum phosphate remains normal.4

Uncontrolled CKD-MBD raises mortality risk in CKD and ESRD, especially in the first 90–120 days of dialysis. Several large observational studies support this association. Among 40,538 hemodialysis patients in a study by Block et al. about the mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients, high serum phosphorus and/or parathyroid hormone (PTH) significantly predicted cardiovascular, fracture-related, and any-cause hospitalizations; high serum phosphorus or calcium and moderate/severe PTH increases predicted mortality.5 A second study followed 22,937 incident dialysis patients for two to four years; serum PTH, phosphorus, and calcium levels not achieving the then-current Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines (PTH 150–300 pg/mL, P 3.5–5.5 mg/mL, Ca x P product <55 mg2/dL2) significantly predicted mortality (see Figure 1).1 Patients with parathyroid hormone (PTH), calcium, and phosphate, all in out-of-target range, had 51% greater risk of dying during follow-up than those with all three indicators within target range (the reference group); patients meeting target for 1 of 3 indicators had a 35%–39% greater risk of death and those meeting target for 2 of the 3 indicators had a 15%–21% greater risk of death than the reference group (see Figure 1a). Risk of death decreased with increasing time on-target for any CKD-MBD parameters (see Figure 1b) .1

(FDA approves new phosphate binder Velphoro for dialysis patients)

In the 1999–2007 Dialysis Outcome Practice Pattern Survey,6 the highest categories of serum phosphorus (6.1–7.0 mg/dL or >7.0 mg/dL) increased mortality risk irrespective of calcium or PTH levels. Finally, prevalent coronary artery calcification at dialysis onset was a significant predictor of mortality in the 44-month prospective Renagel in New Dialysis (RIND) study.7 Existing calcifications progressed significantly more in RIND participants randomized to receive calcium-containing binders for 18 months than in those randomized to sevelamer.8 Thus, based on the evidence presented, management of CKD-MBD may be important to cardiovascular risk management and survival on dialysis.


Management of CKD-MBD

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines9 establish treatment goals and recommendations for managing CKD-MBD. KDIGO suggests maintaining serum phosphate within normal range in stages 3–5 CKD or striving toward normal phosphate levels in ESRD and keeping serum calcium within normal range in all stages. In patients with CKD stages 3–5 not on dialysis, intact PTH levels above normal limits for the assay used should prompt evaluation and correction of hyperphosphatemia, hypocalcemia, and vitamin D deficiency. In dialysis recipients, PTH should be maintained between two and nine times the upper limit of normal for the assay used.

Dietary phosphate and calcium guidance is important in KDIGO-based CKD-MBD management. KDIGO recommends limiting dietary phosphate intake with or without additional treatments for hyperphosphatemia in patients with CKD stages 3–5D.9 The calcium Recommended Daily Allowance for general population adults 51 years and older is 1,200 mg/day; the upper tolerable limit is 2,000 mg/day, according to the Institute of Medicine,10 reflecting cardiovascular risk associated with calcium supplementation from inorganic sources, even in people with normal GFR.11 The U.S. K/DOQI commentary on KDIGO guidelines states, “The [KDIGO] recommendations do not provide a specific amount for the upper limit of a safe amount of calcium intake because there are no trial data to support one.”12 K/DOQI 2003 guidelines had stated, “The total dose of elemental calcium provided by the calcium-based phosphate binders should not exceed 1,500 mg/day (opinion), and the total intake of elemental calcium (including dietary calcium) should not exceed 2,000 mg/day.”13

(Find more articles about Renal Nutrition)

It can be difficult to achieve needed CKD-MBD phosphorus restrictions with diet alone. KDIGO suggests using phosphate binders to treat hyperphosphatemia in patients with CKD stages 3–5. U.S. Food and Drug Administration labeling specifies approval of binder use for hyperphosphatemic patients on dialysis. Phosphate binder use beginning in the first 90 days on dialysis is associated with improved survival.14 Cardiovascular calcifications may predict mortality,7 and calcium-based binders appeared to be associated in the RIND study with accelerated progression of calcification;8 KDIGO considered the evidence inconclusive and called for further research on these points.9 KDIGO suggests restricting the dose of calcium-based phosphate binders in patients with persistent hypercalcemia, arterial calcifications, adynamic bone disease, or persistently low PTH.9

Appropriate phosphate, calcium and vitamin D levels are expected to contribute to maintaining PTH levels within KDIGO guidance. When PTH remains persistently high even after treatment to correct these mineral parameters, calcitriol or active vitamin D analogs are suggested for patients not requiring dialysis; calcitriol, active vitamin D analogs, and/or calcimimetics individually or in combination are suggested for those on dialysis.9


Challenges and solutions in phosphate control

Numerous challenges can obstruct phosphate management. Interdisciplinary team members at our academic dialysis center collaborate with patients and their care partners in novel approaches to improve adherence and success in phosphate control. Engaging patients in this way helps fulfill requirements of the Medicare Conditions of Coverage for ESRD for patients to have opportunities to receive education about treatment and to participate in the planning of their care (494.70 and 494.90).15 Health literacy is important in collaborative phosphate management.16

Patients’ adherence to renal diets may vary or be non-optimal for several reasons. Many protein sources are also high in phosphorus.17 However, recent evidence suggests that phosphorus in plant-based sources of protein is less absorbed than that found in animal-based sources and may allow patients to consume more protein without contributing to increased phosphorus levels.18 Chronic Renal Insufficiency Cohort participants who consumed higher proportions of plant protein had lower serum FGF-23 and higher bicarbonate levels, possibly reflecting alleviated impact on CKD-MBD and acid-base regulation.19 Patients may wish to share mainstream cuisine with CKD-unaffected relatives and friends (as is also reported by people with diabetes who dine with or cook for others.20,21) Mass-market processed foods, which are popular in U.S. diets, are often high in inorganic phosphates, which are more absorbable than naturally occurring phosphates and are underrepresented in labels and nutritional databases.22 Replacement of processed foods with fresh natural ingredients is the ideal but may be resisted by patients.

Nutritionally adherent patients may find long-term persistence with renal diets difficult. Consuming enough protein while controlling daily phosphorus intake can be challenging.18 This problem may be compounded by past dietary approaches striving to lower phosphate by restricting protein, rather than the current emphasis on reducing high-phosphate additives.23 Diets achieving a low phosphorus-to-protein ratio may rely heavily on the lowest-phosphorus protein sources, which patients may find less enjoyable with repetition. Diet alone seldom suffices to treat or prevent hyperphosphatemia.18


Figure 1. Effects of uncontrolled CKD-MBD parameters on mortality risk in a cohort of incident dialysis patients.1 Panel A compares the effects of different combinations of PTH, Ca, and P off-target on mortality; Panel B shows the effects of decreasing durations within target ranges on mortality. Republished with permission of the American Society of Nephrology, from Danese MD, Belozeroff V, Smirnakis K, Rothman KJ. Consistent control of mineral and bone disorder in incident hemodialysis patients. Clin J Am Soc Nephrol 3:1423-9, 2008; permission conveyed through Copyright Clearance Center, Inc.

Nonadherence to or misuse of phosphate binders can further compromise phosphate control. A systematic review has found 22–74% nonadherence rates among patients receiving phosphate binders.24 High-quality social support from renal team members, relatives, and friends is associated with greater adherence. Obstacles to adherence include pill burden, difficulty swallowing, chewing fatigue with chewable binders, or taste aversion. Misunderstandings and incorrect dosing of phosphate binders also occur, for instance, when patients take tablets on an empty stomach. Patients may fail to retain knowledge even of the identities, purposes, and prescribers of their medications. In a 1995 study, only 39% of hemodialysis patients and 57% of peritoneal dialysis patients remembered all of their medications, and only 17% of hemodialysis patients and 24% of peritoneal dialysis patients understood the specific indication for a phosphate binder.25

Regimen knowledge is necessary but not always sufficient for adherence.24 In a survey of reasons for binder nonadherence among 129 patients on hemodialysis and 59 on peritoneal dialysis, 37% of participants reported unawareness of the correct prescription, 30% stated they forgot doses, and 8% cited inconvenience using binders when dining out (see Figure 2).26 Because hyperphosphatemia is asymptomatic, no experiential reinforcement results from binder use (unlike, for example, taking aspirin and getting relief from a headache). Thus, laboratory test feedback and patient counseling on successful phosphate control are essential. The Center for Medicare and Medicaid Services ESRD Quality Incentive Program now requires dialysis clinics to attest that 100% of patients have serum phosphate and calcium tested every month.27

Sevelamer carbonate powder for oral suspension has been demonstrated to be equivalent in phosphate control to sevelamer hydrochloride tablets when dosed at each meal28 and to induce clinically meaningful decreases in serum phosphate even when dosed once-daily with the largest meal29 (see Figure 3). The powder formulation (available in 0.8 g and 2.4 g packets, equivalent to 1 or 3 tablets respectively) provides an additional option for patients who cannot or prefer not to swallow tablets with each meal. Approved labeling specifies suspending each sachet of sevelamer carbonate powder in 60 mL cool water.

Our academic center prescribes predominantly sevelamer carbonate to patients who require phosphate binders, makes extensive use of sevelamer carbonate powder for oral suspension to provide patients a choice of dosage forms, and has explored various administration methods, some of which are off-label. Here we report our experience of patient acceptance, adherence, and phosphate levels during therapy.


Patient education and dosing methods

When our renal team explored how patients actually used their sevelamer (or why they resisted doing so) we gained insight into common dosing errors. Some patients had been applying the dry powder to their tongues (“tastes terrible, too gritty”) or had not stirred powder thoroughly into water before drinking the mixture (powder stuck to the cup bottom). We initially switched patients who reported issues with powder use back to sevelamer carbonate tablets; however, their phosphate control did not come into goal range when using the tablets. A five-minute demonstration by a dietitian resolved our patients’ misunderstandings about powder use.

We have worked with patients prescribed sevelamer carbonate powder to improve concordance, adherence, persistence, and phosphate control outcomes. Concordance is a consultative process in which the patient and health care professional(s) jointly decide on a plan for disease management.30 This approach takes patients’ experience of treatment (which affects sustainability and real-world effectiveness) into account as well as efficacy and safety.21, 30 Concordance is not merely a euphemism for compliance or adherence but a collaborative and non-paternalistic way of planning treatment.21,30 Patients are the experts in their own lives and should be consulted regarding what works for them.21 Engaging patients’ obstacles to medication acceptance and adherence allows design of a more sustainable regimen.

We initiated a trial of therapy on sevelamer powder once a day for a hyperphosphatemic subgroup of patients who had not tolerated other binder options. Among this group who had been 100% out of phosphate goal range, some 60% demonstrated improved phosphorus levels with powder use versus their previous out-of-range levels. We later offered this dosing option to new patients joining our dialysis center; 100% of these new patients initiating once-daily sevelamer powder use as a first-line binder have experienced phosphorus control improvement. Thus, our practice has seen results similar to those in the Fishbane29 study of once-daily powder dosing.


We find that the key factor is patient education. Our patient education segment on sevelamer powder use can be done in 3–5 minutes chair side during dialysis (or when care partners rejoin patients after dialysis) and requires one sachet of sevelamer carbonate powder, a clear plastic glass with 60 mL water, and a spoon. If sevelamer carbonate samples are used, a nurse practitioner must provide them; any/all members of the renal team can participate in subsequent demonstrations. A different voice asking the patient afterward what he or she thought can be a powerful reinforcement.

The demonstrator explains what the drug is for and why it is important, then shows the patient how to open the childproof sachet by folding and tearing along the blue dotted line, pour, and mix it, watching the suspension form and demonstrating how the resin separates from suspension if not mixed immediately before consumption. More medication is in the packet than is needed for the dose to allow for sticking to the sides of the cup. Patients need not retrieve all granules that stick to the sides of the cup after drinking but should stir the mixture up from the bottom if it sits >5 minutes between sips; the texture of the suspension and its propensity to separate are similar to suspensions of powdered fiber laxatives.


Figure 3. Panel A: Serum phosphorus over time in a randomized comparison of thrice-daily sevelamer carbonate powder with thrice-daily sevelamer hydrochloride tablets.28 Reprinted from Fan S, Ross C, Mitra S, et al. A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis. Nephrol Dial Transplant 24:3794-9, 2009, bypermission of the European Renal Association-European Dialysis and Transplantation Association. Panel B: Serum phosphorus over time in a randomized comparison of once-daily sevelamer carbonate
powder with thrice-daily sevelamer hydrochloride tablets. Reprinted from American Journal of Kidney Diseases, volume 55, Fishbane S, Delmez J, Suki WN, et al. A randomized, parallel, open-label study to compare once-daily sevelamer carbonate powder dosing with thrice-daily sevelamer hydrochloride tablet dosing in CKD patients on hemodialysis, pages, 307-15, 2010, with permission from the National Kidney Foundation.

If our patients vocalized dislike for the taste of sevelamer carbonate powder suspended in plain water as directed on the label, some have found suspension with cold water more tolerable than room temperature. If this was not successful for a patient, then potential off-label use of other cold fluids was considered. Patients at our clinic have experimented with mixing the medication with carbonated beverages (grape, orange, or lemon-lime), green tea, flavored water, or Crystal Light instant beverage (first dissolving Crystal Light powder in water, then stirring the sevelamer into the solution; some patients found the mixture too sweet if an entire packet of Crystal Light was used). Some of our patients desired high-phosphate beverages such as cola or milk and elected to mix sevelamer carbonate powder into these to moderate the impact on serum phosphate. Other patients have put sevelamer powder suspension into a water bottle and sipped it all day (e.g., on the road or at work), being certain to shake the bottle before drinking. Some have only achieved phosphate control within goal range by the sipping-all-day method, although it is off-label. Some patients who experienced continued distaste after trying various mixing methods elected to suspend powder in 2–4 ounces of cold water, drink it very quickly, then chase it with the beverage of their choice. Hot liquids (e.g., coffee or tea) cannot be used to dilute sevelamer, as clumping results.

A recent in vitro study31 has used simulated stomach and intestinal pH conditions to examine phosphate binding by sevelamer carbonate powder mixed into foods for different time periods. Tested foods included regular and diet ginger ale, applesauce, reconstituted instant oatmeal, scrambled eggs, baked boneless-skinless chicken breast, and whey protein powder. Phosphate binding was similar whether sevelamer was pre-mixed in and let stand on food for 30 minutes or added to food immediately before simulated digestive tract exposure. Among our patients who have tried adding sevelamer off-label to foods, mixing powder into foods has been successful but sprinkling it on top of foods has been less accepted. Some of our patients have used vanilla pudding or lemon sorbet, either of which has been perceived to combine pleasantly with the citrus flavor of the powder.

The majority of our patients need 2–3 powder packets (2.4 g sevelamer each) once a day to maintain phosphorus levels. Our academic setting takes a step-therapy approach to this dosing so the patient will develop comfort with the medication and what to mix it with. This may take up to one to two weeks, but our data reveals that step-therapy allows patients the control to use the medication and become accustomed to it. Across all phosphate binders, on average 75%–85% of our patients achieve serum phosphate within the K/DOQI range. In a group of our previously hyperphosphatemic (and intolerant or nonadherent to other binders) patients who began a trial of sevelamer carbonate powder therapy with 0% in-range phosphorus, 60% achieved in-range phosphate control on the powder regimen. For comparison, DOPPS 2 data6 had shown that an average of 49.2% of U.S. dialysis patients were within K/DOQI range, and a 1998 retrospective study of U.S. Renal Data Systems cohorts found that 50% of patients had serum phosphorus >6.5 mg/dL.2


Prescriber understanding and intensive patient education on dosing methods with sevelamer powder and consultation has improved concordance and phosphate control for many patients at our academic renal center who had prior histories of nonadherence to approved binder tablet formulations and persistent hyperphosphatemia.

(Find more articles from the November 2013 issue of NN&I)


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15.       Electronic Code of Federal Regulations. Part 494. Conditions for Coverage of End-Stage Renal Disease Facilities. Sections 494.70 and 494.90, 2008. Center for Medicare and Medicaid Services,, accessed August 13, 2012

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24.       Karamanidou C, Clatworthy J, Weinman J, Horne R. A systematic review of the prevalence and determinants of nonadherence to phosphate binding medication in patients with end-stage renal disease. BMC Nephrol 9:2, 2008

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27.       Medicare program; end-stage renal disease quality incentive program. Final rule. Fed Regist 76:627–46, 2011

28.       Fan S, Ross C, Mitra S, et al. A randomized, crossover design study of sevelamer carbonate powder and sevelamer hydrochloride tablets in chronic kidney disease patients on haemodialysis. Nephrol Dial Transplant 24:3794–9, 2009

29.       Fishbane S, Delmez J, Suki WN, et al. A randomized, parallel, open-label study to compare once-daily sevelamer carbonate powder dosing with thrice-daily sevelamer hydrochloride tablet dosing in CKD patients on hemodialysis. Am J Kidney Dis 55:307–15, 2010

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31.       Hanus M, Zhorov E, Brommage D, et al. Assessment of phosphate binding by sevelamer carbonate powder for oral suspension mixed in foods. Nephrol Nurs J 39:239–43, 55, 2012