CompAct - Adherence Series 2014

1
Adherence (Part 1) - The challenge of non-adherence in
hyperphosphatemia
Phosphate binders have been shown to be effective in regulating phosphorus
levels1,2
and yet according to a recent large observational study,3
50% of patients
have serum phosphorous concentrations outside the target range. Clinical studies
have demonstrated the efficacy of phosphate binders in controlling serum
phosphorus and observational studies confirm their widespread use,1
so to what
extent is the difficult of controlling phosphorus levels caused by non-adherence to
binder regimens?4
Phosphate binders have shown to be effective at controlling phosphorus levels
Phosphate binders are widely used in dialysis patients to control phosphate levels
and observational studies have shown their use to be associated with improved
survival outcomes.
• In a study of 6,797 dialysis patients Cannata-Andia et al. found that patients
prescribed phosphate binders had 29% lower all-cause mortality risk and a
22% lower cardiovascular mortality risk.1
• Treatment with phosphate binders was independently associated with
decreased mortality in an observational study of 10,044 incident dialysis
patients.2
Despite the widespread use of binders, phosphorus levels in general are poorly
controlled, with 50% of patients in a recent study3
found to have poorly controlled
phosphorus levels at baseline. One possible reason for this is the underestimation of
the amount of highly absorbable, ‘hidden’ phosphorus in Western diets, which has
been shown to be particularly high in processed foods.5
Alongside this, there is also
a growing body of evidence highlighting that many dialysis patients are not adhering
to their binder medication.

2
Evidence suggests patient adherence to phosphate binders is poor
Non-adherence is a problem in many chronic diseases, but can be especially
challenging for dialysis patients due to a complex treatment regimen involving both
dietary restrictions and multiple medications. Numerous studies have shown that the
prevalence of patient non-adherence to phosphate binder treatments is high:
• A survey in 2010 found 76% of nephrologists and 63% of dialysis staff thought
non-adherence was the main reason for poor control of phosphorus levels in
patients.6
• In a cross-sectional study, 502 haemodialysis patients responded to a
questionnaire with approximately 70% stating they were non-adherent to
phosphate binders.7
• A recent study of Spanish dialysis patients found that 60% were non-adherent
to their phosphate binder treatment regimens.8
• In another study by the same author, results found that in 165 dialysis
patients, 40% were non-adherent to their treatments and 21% admitted non-
adherence to phosphate binders.9
• A systemic review of 34 studies found non-adherence rates averaged at 51%
and ranged from 22% to 74%. The result of this review highlighted the
variability in measures of adherence.10
These data suggest that non-adherence is an important issue in phosphate binder
therapy and it is a logical step to suggest that improving these adherence rates could
lead to better treatment outcomes for dialysis patients.
This is the first in a series of articles discussing adherence, outcomes & pill
burden in hyperphosphatemia. In our next article we will look at associations
between adherence and improved outcomes.

3
References
1. Cannata-Andía JB, Fernández-Martín JL, Locatelli F, et al. Use of phosphate-binding agents is
associated with a lower risk of mortality. Kidney Int. 2013;84(5):998-1008. doi:10.1038/ki.2013.185.
2. Isakova T, Gutiérrez OM, Chang Y, et al. Phosphorus binders and survival on hemodialysis. J Am
Soc Nephrol JASN. 2009;20(2):388-396. doi:10.1681/ASN.2008060609.
3. https://www.compact-renal.com/2013/06/11/era-edta-2013-cosmos-strengthens-our-understanding-
of-the-relationship-between-bone-mineral-parameters-and-mortality-risk/ (last seen on June 6
th
, 2014)
4. Covic A, Rastogi A. Hyperphosphatemia in patients with ESRD: assessing the current evidence
linking outcomes with treatment adherence. BMC Nephrol. 2013;14:153. doi:10.1186/1471-2369-14-
153.
5. Carrigan A, Klinger A, Choquette SS, et al. Contribution of Food Additives to Sodium and
Phosphorus Content of Diets Rich in Processed Foods. J Ren Nutr. 2014;24(1):13-19.e1.
doi:10.1053/j.jrn.2013.09.003.
6. Toussaint ND, Pedagogos E, Beavis J, Becker GJ, Polkinghorne KR, Kerr PG. Improving CKD-
MBD management in haemodialysis patients: barrier analysis for implementing better practice.
Nephrol Dial Transplant. 2010:gfq602. doi:10.1093/ndt/gfq602.
7. Martins MTS, Silva LF, Kraychete A, et al. Potentially modifiable factors associated with non-
adherence to phosphate binder use in patients on hemodialysis. BMC Nephrol. 2013;14(1):208.
doi:10.1186/1471-2369-14-208.
8. Dolores Arenas M, Pérez-García R, Bennouna M, et al. Improvement of therapeutic compliance in
haemodialysis patients with poor phosphorus control and adherence to treatment with binders:
COMQUELFOS study. Nefrol Publ Of Soc Esp Nefrol. 2013;33(2):196-203.
doi:10.3265/Nefrologia.pre2012.Oct.11726.
9. Arenas MD, Malek T, Gil MT, Moledous A, Alvarez-Ude F, Reig-Ferrer A. Challenge of phosphorus
control in hemodialysis patients: a problem of adherence? J Nephrol. 2010;23(5):525-534.
10. 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. 2008;9(1):2. doi:10.1186/1471-2369-9-2.

4
Adherence (Part 2) - Is adherence to phosphate binder therapy
associated with improved outcomes?
Research and clinical experience suggests that adherence to phosphate binders is
low, but will improving adherence lead to better outcomes? A meta-analysis of 21
studies, in diseases such as HIV, myocardial infarction and type II diabetes, found
that “good adherence to drug therapy is associated with positive health outcomes.”1
But does similar evidence exist for adherence to phosphate binder treatment?
Non-adherence is associated with poor control of phosphorus levels
A number of studies have examined the association between adherence to
phosphate binders and serum phosphorus levels. From the recent literature:
• Arenas et al. found that haemodialysis patients who were non-adherent to
phosphate binders were significantly more likely to have high phosphorus than
adherent patients. Non-adherence to phosphate binders was greater than for
hypotensive agents, suggesting dialysis patients may have increased
difficulty following binder regimens.2
• A study of 76 peritoneal dialysis patients found adherence to phosphate
binders was greatest in patients with low phosphorus levels. Multivariate
analysis showed adherence was the only significant contributor to high
serum phosphorus levels.3
• In an analysis of 8,616 patients, lower adherence was associated with higher
mean phosphorus levels and a lower percentage of patients with serum
phosphorus ≤5.5 mg/dL.4
• At ASN Kidney Week 2012, Tentori et al. presented an analysis of the
DOPPS5
registry showing non-adherence to phosphate binders was
associated with high phosphorus and PTH levels.
Studies such as these suggest that improved adherence may lead to a greater
control of serum phosphorus, and a reduced risk of hyperphosphatemia. Given the
well-documented links between high serum phosphorus levels and increased
mortality in dialysis patients,6
it seems likely that improving adherence to phosphate
binders will have a positive effect on hard outcomes, similar to that seen from
improved adherence in other diseases.

5
Improving adherence may also deliver financial benefits
Poor adherence could also be leading to over-prescription of phosphate binders and
a higher pill burden, as physicians escalate their attempts to control high phosphorus
levels.7
This over-prescription also has the potential to increase medication cost. A
recent review focusing on the cost of adherence in multiple disease areas concluded
that non-adherence is a significant contributor to avoidable healthcare costs in the
US, and improving adherence could save “billions of dollars” per year.8
But how to improve adherence?
Evidence suggests that improved adherence to phosphate binders could improve
outcomes and potentially lower medication costs. But how can clinicians improve
adherence? The starting point for this analysis needs to be an understanding of why
patients are not adhering to phosphate binders, and this will be the focus of our next
few articles on COMPACT Renal.

6
References
1. Simpson SH, Eurich DT, Majumdar SR, et al. A meta-analysis of the association between
adherence to drug therapy and mortality. BMJ. 2006;333(7557):15. doi:10.1136/bmj.38875.675486.55.
3. Hung K-Y, Liao S-C, Chen T-H, Chao M-C, Chen J-B. Adherence to phosphate binder therapy is
the primary determinant of hyperphosphatemia incidence in patients receiving peritoneal dialysis. Ther
Apher Dial Off Peer-Rev J Int Soc Apher Jpn Soc Apher Jpn Soc Dial Ther. 2013;17(1):72-77.
doi:10.1111/j.1744-9987.2012.01098.x.
4. Wang S, Alfieri T, Ramakrishnan K, Braunhofer P, Newsome BA. Serum phosphorus levels and pill
burden are inversely associated with adherence in patients on hemodialysis. Nephrol Dial Transplant
Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2013. doi:10.1093/ndt/gft280.
5.http://www.abstracts2view.com/asn_2012/view.php?nu=785&terms=&type=abstract (last seen on
June 6
th
, 2014)
6. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism,
mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol JASN. 2004;15(8):2208-
2218. doi:10.1097/01.ASN.0000133041.27682.A2.
7. Chiu Y-W, Teitelbaum I, Misra M, Leon EM de, Adzize T, Mehrotra R. Pill Burden, Adherence,
Hyperphosphatemia, and Quality of Life in Maintenance Dialysis Patients. Clin J Am Soc Nephrol.
2009. doi:10.2215/CJN.00290109.
8. Iuga AO, McGuire MJ. Adherence and health care costs. Risk Manag Healthc Policy. 2014;7:35-44.
doi:10.2147/RMHP.S19801.

7
Adherence (Part 3) - Why do patients not adhere to therapies?
A high percentage of dialysis patients do not adhere to their phosphate binder
medication, which leads to poor control of serum phosphorus levels. What factors
contribute to this non-adherence?
Adherence is a multi-factorial problem
Studies investigating the causes of non-adherence across multiple diseases have
found it to be a multifactorial problem. Not only do adherence rates vary between
patients, they also vary for the same individual over time and across treatments.1
In
fact, most patients are non-adherent at some point in time. 1
Some of the reasons
found for non-adherence to therapies are:
Psychological factors
• Psychosocial factors include patients’ beliefs about their treatment, the
amount of social support they receive and even certain personality traits.
• A systematic review of 34 studies on adherence to phosphate binders found
that psychosocial factors were the most promising predictors of non-
adherence.2
However, pill burden as a predictor of adherence was not
assessed in this review.2
Need for lifestyle modification
• One study found adherence to binders to be lowest in patients who had to
change their lifestyle in order to adhere.3
Cost-to-patient of medication
• In a review of 160 articles, across multiple diseases, on the relationship
between treatment costs-to-patient and adherence, increases in patient cost
sharing were associated with declines in medication adherence, which in turn
were associated with worse health outcomes.4
Demographic variables
• Demographic factors such as age, gender, education and ethnicity have all
been suggested as factors that can influence adherence.
• However, in a systematic review of studies related to phosphate binders, only
age was associated with adherence.2

8
Some factors are particularly relevant to phosphate binder treatment
Two potential causes of non-adherence have particular relevance for patients
prescribed phosphate binders.
High pill burden, combined with regimen complexity
• Dialysis patients have a high pill burden. One study estimated the average pill
burden to be nineteen pills per day, of which phosphate binders contributed
about half. 5
Phosphate binder regimens are also relatively complex, involving
multiple doses per day administered with meals.5
• A recent study has shown that a lower pill burden was associated with greater
adherence.6

9
Medication preference and poor tolerability of binders
• One study found that non-adherence to phosphate binders was associated
with medication preferences. Perhaps unsurprisingly, patients on a phosphate
binder that they did not like showed lower adherence than patients who did
like their treatment.7
• This is a particularly significant factor in haemodialysis patients as many
binders have relatively poor tolerability over time, with patient-reported side
effects a common reason for binder discontinuation.8
Both tolerability and pill burden appear to be practical, modifiable targets for
improving adherence in hyperphosphatemic patients. We will examine these issues
in greater detail in our next articles.
References
1. Horne R, Weinman J, Barber N, Elliott R, Morgan M. Concordance, Adherence and Compliance in
Medicine Taking: Report for the National Co-ordinating Centre for NHS Service Delivery and
Organisation R & D (NCCSDO). NCCSDO; 2005. Available at:
http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0009/64494/FR-08-1412-076.pdf.
2. 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. 2008;9(1):2. doi:10.1186/1471-2369-9-2.
4. Eaddy MT, Cook CL, O’Day K, Burch SP, Cantrell CR. How patient cost-sharing trends affect
adherence and outcomes: a literature review. P T Peer-Rev J Formul Manag. 2012;37(1):45-55.
2009. doi:10.2215/CJN.00290109.
7. Arenas MD, Rebollo P, Malek T, et al. A comparative study of 2 new phosphate binders (sevelamer
and lanthanum carbonate) in routine clinical practice. J Nephrol. 2010;23(6):683-692.
8. Wang S, Anum EA, Ramakrishnan K, Alfieri T, Braunhofer P, Newsome B. Reasons for phosphate
binder discontinuation vary by binder type. J Ren Nutr Off J Counc Ren Nutr Natl Kidney Found.
2014;24(2):105-109. doi:10.1053/j.jrn.2013.11.004.

10
Adherence (Part 4) - Why do patients not adhere to phosphate
binders: poor tolerability?
Poor drug tolerability may be a reason why more than half of dialysis patients, on
average, do not adhere to phosphate binder medication.1
With the range of available
phosphate binders likely to expand in the next year,2
physicians may be able to
improve adherence by selecting more appropriate binders for their patients.
A recent paper by Wang et al. identified poor toleration of side-effects as a major
reason for discontinuation of phosphate binder treatment.1
In this study, 30,933
patient records were retrospectively analysed to assess the reasons behind
phosphate binder discontinuation. 50% of records did not contain a reason for
discontinuation and 27% of discontinuations were due to “lab results”. In this latter
category, hypophosphatemia (42%) and hypercalcemia (24%) were the largest
attributed causes of discontinuation due to lab results.
11% of discontinuations, the next largest cohort, were due to “patient not tolerating”
and further analysis of this group presented some interesting findings. Nearly 48% of
these patients discontinued therapy due to gastrointestinal upset and there was
noticeable variation in the reasons for discontinuation between specific binders.
Poor tolerability of binders may be a modifiable cause of non-adherence
While discontinuing therapy, and noting this in the patient record, does not equate to
non-adherence, there is likely to be a high degree of overlap between the two factors.
Results from a cross-sectional study of approximately 500 patients support this
relationship between adherence and tolerability. Almost 15% of patients who were
classified as non-adherent in this study (and approximately 6% of those classified as
adherent) reported that they always or almost always stopped taking phosphate
binders on their own initiative after “feeling worse”.3
This intentional non-adherence to therapy may be modifiable with closer
consideration of the side effects of particular binders. The Wang et al. study
highlights some factors that clinicians may wish to consider when selecting a
phosphate binder for an individual patient. Such individualization of treatment could
be rewarded with increased medication adherence and, potentially, improved
outcomes. This process is also likely to be supported in future by a wider range of
available therapy options, with different tolerability profiles.2

11
References
1. Wang S, Anum EA, Ramakrishnan K, Alfieri T, Braunhofer P, Newsome B. Reasons for phosphate
binder discontinuation vary by binder type. J Ren Nutr Off J Counc Ren Nutr Natl Kidney Found.
2014;24(2):105-109. doi:10.1053/j.jrn.2013.11.004.
2. Ketteler M, Biggar PH. Use of phosphate binders in chronic kidney disease: Curr Opin Nephrol
Hypertens. 2013;22(4):413-420. doi:10.1097/MNH.0b013e32836214d4.
3. Martins MTS, Silva LF, Kraychete A, et al. Potentially modifiable factors associated with non-
adherence to phosphate binder use in patients on hemodialysis. BMC Nephrol. 2013;14(1):208.
doi:10.1186/1471-2369-14-208.

12
Adherence (Part 5) - Why do patients not adhere to phosphate
binders: high pill burden?
Pill burden is recognized as a factor that can affect adherence in a number of
diseases, such as HIV.1
For dialysis patients, the daily pill intake is very high, with a
large proportion of this burden comprised of phosphate binders.2
Given that non-
adherence to phosphate binders is common, is there evidence that shows a direct
association between pill burden and adherence in dialysis patients?
Studies show that high pill burden affects adherence in phosphate binder
treatment
In a cross-sectional study of 233 US dialysis patients, Chiu et al. found that 62% of
patients were non-adherent and adherence decreased significantly with pill count.2
The study results also suggested that low adherence could lead to over-prescription
of phosphate binders and so to a greater pill burden. This clinical approach
potentially creates a self-fulfilling, repeating cycle of low adherence, poor phosphorus
control and dose escalation.

13
Importantly, overall pill burden was associated with a low physical component
summary score of the SF-36 QoL (Quality of Life) assessment. Increasing the
number of pills prescribed did not improve control of serum phosphorus levels and
further reduced the patient’s quality of life assessment. 2
Recently, Wang et al also found that increasing pill burden was associated with non-
adherence, and non-adherence in turn was associated with poorly controlled serum
phosphorus levels.3
Using data from a pharmacy management program, the
investigators tracked dialysis patients on phosphate binder monotherapy over time.
8,616 haemodialysis patient records were analysed, and their medication possession
ratio (MPR) and pill burdens were calculated.
The Medication Possession Ratio is the proportion of days the patient has
sufficient medication available to have taken the medication as prescribed. It is
commonly used as an indirect measure of adherence, with a low MPR implying
low adherence. An MPR of 100% would suggest perfect adherence.
The Wang et al. study found that:
• Weighted MPR levels were low overall, ranging from 51% to 42% in different
cohorts ,
• MPR increased as pill burden decreased, with adherence strongest (51%) in
the group with the lowest pill burden (0-3 pills per day), and
• Higher MPR was associated with worse control of phosphorus to target
ranges.
These results suggest that a lower pill burden results in greater adherence and lower
phosphorus levels. The MPR levels of 40% to 50% align well with other real-world,
medication adherence data, lending eight to this observational study.
While high pill burden is only one of several factors that may be contributing to poor
adherence in dialysis patients, reducing this pill burden is a practical and achievable
goal. Switching the type of binders used in patients to those which require less pills
per day may deliver some of the improvements in adherence and outcomes that
clinicians are seeking.

14
References
1. Nachega JB, Parienti J-J, Uthman OA, et al. Lower Pill Burden and Once-daily Dosing Antiretroviral
Treatment Regimens for HIV Infection: A Meta-Analysis of Randomized Controlled Trials. Clin Infect
Dis Off Publ Infect Dis Soc Am. 2014. doi:10.1093/cid/ciu046.
2009. doi:10.2215/CJN.00290109.

15
Adherence (Part 6) - Improving adherence through treatment
optimization and simplifying regimens
Patients can find it challenging to adhere to complicated treatment regimens. For
example, elderly patients who have cognitive or memory impairments may find
therapy compliance difficult,1
and younger patients may struggle to adapt their
lifestyle to treatment demands.2
This article will look at different ways in which
treatment strategies can be adjusted in order to reduce regimen complexity and
potentially improve adherence.
Simplifying dosing demands
Kripalani et al. analysed 37 randomized controlled trials, across multiple chronic
diseases, which described interventions intended to enhance patient adherence to
self-administered medications. The review found that the most effective approaches
were behavioural interventions that simplified dosing demands.3
A systematic review of 76 studies also showed that simpler, less frequent dosing
regimens are associated with better adherence in a variety of diseases.4
Similarly, a
Cochrane Review of hypertensive patients also found that reducing the number of
daily doses increases adherence.5
However, reducing the frequency of phosphate binder dosing is particularly
challenging as pills must be taken at every meal. Despite this it may be possible to:
1. Reduce the number of phosphate binders that need to be taken at each meal,
and
2. Rationalize the dosing regimens of binder and non-binder medications, for
example by equating a “morning” dose to “with breakfast”.
Reminder systems
A randomized clinical trial found that a personalized cell phone reminder system was
capable of improving adherence to antiretroviral therapy in 23 HIV patients.6
Similarly
a Cochrane review of interventions to improved adherence to lipid lowing drugs found
that the most effective interventions were based on reminder systems.7
Dose packaging strategies
A systematic review of the adherence benefits of packaging pills with a calendar
and/or pill organisers found that six out of ten trials reported higher adherence.
However in only one study did this relate to clinically significant improvement.8

16
Individualized treatment plans
Healthcare professionals can also draft specific treatment plans for patients. A
Cochrane review by Gray et al. showed that individualized care planning improved
adherence in glaucoma patients.9
Personal treatment plans may also have greater
importance in patients with multiple comorbidities, where each condition has its own
treatment regimen. Pharmacists have an increasing role to play in developing these
plans, through programs such as Medicare’s Medication Therapy Management.10
References
1. Andrade ASA, McGruder HF, Wu AW, et al. A programmable prompting device improves
adherence to highly active antiretroviral therapy in HIV-infected subjects with memory impairment. Clin
Infect Dis Off Publ Infect Dis Soc Am. 2005;41(6):875-882. doi:10.1086/432877.
2. Horne R, Weinman J, Barber N, Elliott R, Morgan M. Concordance, Adherence and Compliance in
Medicine Taking: Report for the National Co-ordinating Centre for NHS Service Delivery and
Organisation R & D (NCCSDO). NCCSDO; 2005. Available at:
http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0009/64494/FR-08-1412-076.pdf.
3. Kripalani S, Yao X, Haynes RB. Interventions to enhance medication adherence in chronic medical
conditions: a systematic review. Arch Intern Med. 2007;167(6):540-550.
doi:10.1001/archinte.167.6.540.
4. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens
and medication compliance. Clin Ther. 2001;23(8):1296-1310.
5. Schroeder K, Fahey T, Ebrahim S. Interventions for improving adherence to treatment in patients
with high blood pressure in ambulatory settings. Cochrane Database Syst Rev. 2004;(2):CD004804.
doi:10.1002/14651858.CD004804.
6. Hardy H, Kumar V, Doros G, et al. Randomized controlled trial of a personalized cellular phone
reminder system to enhance adherence to antiretroviral therapy. AIDS Patient Care STDs.
2011;25(3):153-161. doi:10.1089/apc.2010.0006.
7. Schedlbauer A, Davies P, Fahey T. Interventions to improve adherence to lipid lowering medication.
Cochrane Database Syst Rev. 2010;(3):CD004371. doi:10.1002/14651858.CD004371.pub3.
8. Zedler BK, Kakad P, Colilla S, Murrelle L, Shah NR. Does packaging with a calendar feature
improve adherence to self-administered medication for long-term use? A systematic review. Clin Ther.
2011;33(1):62-73. doi:10.1016/j.clinthera.2011.02.003.
9. Gray TA, Orton LC, Henson D, Harper R, Waterman H. Interventions for improving adherence to
ocular hypotensive therapy. Cochrane Database Syst Rev. 2009;(2):CD006132.
doi:10.1002/14651858.CD006132.pub2.
10. http://www.cms.gov/Medicare/Prescription-Drug-Coverage/PrescriptionDrugCovContra/MTM.html
(last seen on May 22
nd
, 2014)

17
Adherence (Part 7) - Improving adherence through increased
patient education
Educational interventions have been found to increase adherence in multiple
diseases, although reported effects have been inconsistent and studies have largely
been short-term.1
In this article we review whether patient education can similarly
improve adherence to phosphate binder medication.
Educational programmes can improve patient adherence
Several studies have shown that educational sessions or programs regarding
phosphate management have led to improved adherence and/or treatment
outcomes.
• In a randomized controlled trial of 56 dialysis patients, those who attended
one-to-one teaching sessions, aimed at improving patients’ knowledge of
phosphate management, showed a significant reduction in serum phosphorus
concentrations compared to control.2
• Gardulf et al. studied 43 CKD patients (most on dialysis) attending a 2-month
educational program regarding calcium and phosphate balance, food intake
and phosphate binders. The group exhibited significantly reduced plasma
phosphate for up to 12 months afterwards.3
• A nurse-led educational and counselling session provided to 41 patients on
phosphate binders resulted in an increase in adherence from 83% to 94%
after 13 weeks. The control group’s adherence decreased from 86% to 76%.4
• Another nurse-led education program over 12 weeks saw a significant
improvement in the proportion of patients who took their phosphate binder
correctly, increasing from 44 to 72%, although this did not lead to a statistically
significant change in clinical markers.5
• A “Phosphate Education Program” in children with CKD used ‘phosphorus
units’ to allow patients to quickly estimate phosphorus content in foods and
self-adjust binder dosing. Within 6 weeks after training, the percentage of
children with serum phosphate outside of the target range dropped from 63%
to 31%.6
While these studies suggest benefits from patient education regarding phosphate
management, there is a clear need for a randomized controlled trial evaluating
educational interventions over an extended period. This is in line with a 2008
Cochrane Review of interventions for enhancing adherence across multiple
conditions, which concluded that “high priority should be given to fundamental and
applied research concerning innovations to assist patients to follow medication
prescriptions for long-term medical disorders.”1

18
Patients would like more information about phosphate management
This need for further research is especially apparent when we consider patients’
current levels of understanding about their treatment goals. In one study, 84% of
surveyed patients had heard of phosphate, but 42% were unsure of high phosphate
foods and 46% were unaware of consequences of elevated phosphate.7
This
Australian study also revealed an interesting symmetry between patients and
nephrologists:
• 74% of patients wanted to know more about CKD-MBD (40% via written
material),
• 84% of nephrologists believed that their patients wanted to know more about
CKD-MBD, but
• Only 28% provided written patient materials on CKD-MBD.
Adherence to phosphate binders: a quick summary
We have reviewed the topic of adherence over the past few weeks on COMPACT
Renal. In summary:
• Adherence to phosphate binder therapies in dialysis patients is poor, with
approximately half of patients non-adherent
• Non-adherence to phosphate binders is associated with poor control of serum
phosphorus which is associated in turn with worse disease outcomes
• While non-adherence is a complex, multifactorial problem, there are a number
of potentially modifiable factors that clinicians could address in order to
improve compliance
• Reducing pill burden and optimizing therapies to improve tolerability are two
possible approaches that may bring specific benefits in dialysis patients
• Simplifying dosing regimens and improving patient education may also lead to
improved medication adherence

19
References
1. Haynes RB, Ackloo E, Sahota N, McDonald HP, Yao X. Interventions for enhancing medication
adherence. In: Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd; 2008.
2. Ashurst I de B, Dobbie H. A randomized controlled trial of an educational intervention to improve
phosphate levels in hemodialysis patients. J Ren Nutr Off J Counc Ren Nutr Natl Kidney Found.
2003;13(4):267-274.
3. Gardulf A, Pålsson M, Nicolay U, Swedish Renal Nurse Group. Education for dialysis patients
lowers long-term phosphate levels and maintains health-related quality of life. Clin Nephrol.
2011;75(4):319-327.
4. Van Camp YP, Huybrechts SA, Van Rompaey B, Elseviers MM. Nurse-led education and
counselling to enhance adherence to phosphate binders. J Clin Nurs. 2012;21(9-10):1304-1313.
doi:10.1111/j.1365-2702.2011.03967.x.
5. Sandlin K, Bennett PN, Ockerby C, Corradini A-M. The impact of nurse-led education on
haemodialysis patients’ phosphate binder medication adherence. J Ren Care. 2013;39(1):12-18.
doi:10.1111/j.1755-6686.2013.00343.x.
6. Ahlenstiel T, Pape L, Ehrich JHH, Kuhlmann MK. Self-adjustment of phosphate binder dose to meal
phosphorus content improves management of hyperphosphataemia in children with chronic kidney
disease. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2010;25(10):3241-
3249. doi:10.1093/ndt/gfq161.
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20
Adherence (Part 8) – CompAct expert view: Dr Stuart Sprague on
the importance of low pill burden in the treatment of
hyperphosphatemia
In a new video interview for COMPACT, Dr Stuart Sprague from the University of
Chicago discusses the optimal approach to phosphate management in dialysis
patients. Dr Sprague highlights that effective, tolerable, and low pill burden
phosphate binders are key to patient adherence in this highly medicated patient
population.
Transcript
Hello, I'm Dr Stuart Sprague. I'm currently at North Shore University Health Systems
and on the faculty at University of Chicago Pritzker School of Medicine.
I'd like to take a few minutes right now and talk to you about the optimal, integrated
approach towards phosphate management in dialysis patients.
I'm sure we all realize that regulating serum phosphate is very important for a
patient's optimal health and outcome, and it's become a very difficult aspect for many
patients to do. Generally, the integrated approach toward phosphate management
includes:
• Dietary counselling and the restriction of foods that are high in inorganic
phosphates, without excessively restricting protein.
• The use of adequate dialysis.
• The appropriate use of medication, such as vitamin D compounds so we don't
enhance phosphate absorption.
• Appropriate management of parathyroid hormone and adequate dialysis.
However, the mainstay and probably the most important feature of taking care of
these patients is that of using phosphate binders.
When we want to approach phosphate binders, we want to make sure that they have
low GI side effects, that patients do tolerate them, and that they're able to take them
with their meals, and probably one of the biggest aspects is that of patient
compliance and adherence, [which is related to] the number of phosphate binders the
patient has to take.

21
If we consider that many dialysis patients take well over 20 pills a day, and frequently
half of those pills are phosphate binders, we then can appreciate how difficult it may
be for patients to become compliant or adherent with their phosphate binders, as it
becomes difficult to take 2, 3, or 4 pills with each meal, especially these pills that
affect the taste of the meal in a negative way.
So therefore, patient adherence and compliance is something that we have to
accomplish by using phosphate binders that are effective, tolerable, and require a
low pill burden. Having patients having a low pill burden will then enhance their ability
to take these binders as prescribed.

CompAct - Adherence Series 2014

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