Phosphate-control adherence in hemodialysis patients: current perspectives

Figures & data

Table 1 Overview of currently available phosphate binders

Phosphate binder	Mechanism of action	Typical daily pill burden*	Advantages	Disadvantages
Aluminum salts	Aluminum binds to phosphates and forms insoluble precipitate in the GI tract; aluminum hydroxide also forms compounds with phosphate ions in the blood	No safe dose identified	Effective, inexpensive	Associated with cognitive disturbances, osteomalacia, and anemia. Patient requires careful monitoring
Calcium acetate (eg, Phosex)	Dissociations in the GI tract; calcium binds to phosphates and forms insoluble precipitate	4–6 pills (1,000 mg each, equivalent to 250 mg calcium) per day	Effective and inexpensive	Potential for increased hypercalcemia; could lead to vascular calcification; high pill burden
Calcium carbonate (eg, Calcichew)	Dissociation in the GI tract; calcium binds to phosphates and forms insoluble precipitates	Pill number as prescribed per day, (1,250 mg each, equivalent to 500 mg calcium)	Effective and inexpensive	Potential for increased hypercalcemia; could lead to vascular calcifications; high pill burden
Calcium acetate/magnesium carbonate	Dissociation of the active compounds calcium acetate and magnesium carbonate in the GI tract; each binds to phosphate and forms insoluble precipitates	Total: 3–10 pills per day (each pill contains 435 mg calcium acetate/235 mg magnesium carbonate)	Lower calcium uptake versus calcium-based binders; effective; moderate costs	Monitoring of magnesium level required; in some circumstances, moderate increase in serum magnesium level
Sevelamer HCl	Anion exchange resin that exchanges chloride ions for phosphate ions	3 pills (800 mg each) three times daily (total: 9 pills/days)	Effective; lipid-lowering effect; potential cardioprotective effect	Expensive; high pill burden; associated with GI side effects such as abdominal bloating, diarrhea, and constipation. Potential development of metabolic acidosis
Sevelamer carbonate	Anion exchange resin that exchanges chloride ions for phosphate ions	3 pills (800 mg each) three times daily (total: 9 pills/day)	Effective; lipid-lowering effect; potential cardioprotective effect; available as a powder, which may reduce pill burden	Expensive; high pill burden; associated with GI side effects
Lanthanum carbonate	Dissociation in the upper GI tract; lanthanum then binds to phosphates and forms insoluble, nonabsorbable lanthanum phosphate complexes	1 pill (500, 750, or 1,000 mg) three times daily (total: 3 pills/day)	Effective, low pill burden	Expensive; associated with GI side effects such as nausea, vomiting
Sucroferric oxyhydroxide	Ligand exchange between the hydroxyl groups in the sucroferric oxyhydroxide and phosphorus in food lead to elimination of bound phosphate in the stool	3 pills (1,500 mg daily)	Effective, reduced pill burden relative to sevelamer Iron is not absorbed; does not lead to iron overload	Discolored feces, diarrhea, nausea Does not affect the hemoglobin level
Ferric citrate	Increases stool phosphate excretion and reduces intestinal phosphate absorption	6 pills (6,000 mg daily)	Effective, positive hematologic effects; Iron is absorbed	Discolored feces, diarrhea, nausea; Risk of iron overload; Potential risk of aluminum absorption

Notes:

* Timing and dose of phosphate binder to be adjusted in line with timing of meal/snacks and the phosphorus content thereof. Copyright ©2013. Covic and Rastogi; licensee BioMed Central Ltd. Reproduced with permission from Covic A, Rastogi A. Hyperphosphatemia in patients with ESRD: assessing the current evidence linking outcomes with treatment adherence. BMC Nephrol. 2013;14(1):153.¹¹

Abbreviations: GI, gastrointestinal; HCl, hydrochloride.

Table 2 Factors associated with nonadherence and summary of relevant associations (N=38)

Factors	No of studies	Significant association with measures of nonadherencea
		Pre-dialysis phosphorus	Patient self-report	Pill count/medication event monitoring system
Sociodemographic variables
Age	27
Younger		8	8
Older		1	2	1
Gender	22
Male			1
Female			2
Low education (high school)	15		1
Ethnicity (non-Caucasian)	7	1	1	2
Marital status (single, divorced, or widowed)	6		2
Employment status (unemployed)	6		1
Support from healthcare provider	2		2
Family problems (illness interfering with family life)	2		1
Smoker	1	1
Clinical variables
Long-term on hemodialysis	16		3
Comorbidity (DM, HTN)	9	1	1
Number of hospitalizations	2		1
Psychosocial variables
Depressive symptoms	6		4
Beliefs about medicine	5
Concern		1	2
Benefit		1	1
Necessity		1	3
Necessity–concern differential score			2
Health locus of controlb	3	2	1
Autonomous			1
Doctors			1
Emotional representation	1	1
Medication-related factors
Knowledge about medicine	5	1	1
Number of prescribed medicines	3			1
Daily tablet count	2	1	1
Total number of PB prescribed	2	1	1
Total pill burden	2
Pill burden from PB	1			1
PB equivalent dosage	1		1
Regimen complexity (frequency and dosage)	1	1
Drug coverage by insurance	1			1
Healthcare cost (inpatient)	1			1

Notes:

a Level of significance (p < 0.05, p < 0.01, and p < 0.001) varies between studies.

b Defined as having high expectation that one’s actions will have a causal relationship with the consequences produced. Copyright ©2015. PLOS. Reproduced from Ghimire S, Castelino RL, Lioufas NM, Peterson GM, Zaidi ST. Nonadherence to medication therapy in haemodialysis patients: a systematic review. PLoS One. 2015;10(12):e0144119.¹²

Abbreviations: DM, diabetes mellitus; HD, hemodialysis; HTN, hypertension; PB, phosphate binders.

Figure 1 Psychosocial predictors of nonadherence to phosphate-binding medication assessed by two or more studies.

Note: ©2008. BioMed Central Ltd. Adapted from Karamanidou et al; licensee BioMed Central Ltd. 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;9:2.¹⁰

Table 3 Motivational interviewing

Motivational factor	Objective	Example	Follow-up
1. Express empathy	To establish rapport and avoid resistance by demonstrating understanding of the patient’s situation	Patient expresses difficulty making all these changes	Remind the patient that current levels put them at risk for more serious diseases
2. Roll with resistance	Avoid magnifying resistance by allowing patient to explore their barriers in a nonjudgmental supportive manner	Patient is reluctant to continue medication since it is hard to remember to take and they no longer feel unwell	Ask the patient where they see themselves in 6 months if they stop taking the medication
3. Elicit/provide reminder/elicit	Find out what the patient already knows, fill in the gaps or correct misconceptions, and explore how the change you suggest will fit into the patient’s life	Elicit: ask patient what they know about managing their CKD	Reminder: for example, to take statins and closely monitor blood pressure Elicit: “what do you think the biggest barrier is for you right now in managing this condition?”
4. Support autonomy	To reduce resistance by assuring patients you know you can’t make them do anything – it is their choice	Emphasize to patient that it is their choice but as their doctor you are concerned if they do not try medication	Reiterate that it is the patient’s choice and they need to consider all the options. Reassure patient that if they do decide to try a particular medication they will be regularly monitored for side effects and dose adjusted accordingly
5. Explore ambivalence	Help patient consider pros and cons of change in a relaxed yet systematic manner	Encourage a discussion about the pros and cons, eg, eating egg whites as part of a low-phosphorus diet	Summarize current situation with the patient and explain that the benefits will outweigh the potential drawbacks associated with an egg-white diet
6. Elicit change talk	To evoke the patient’s reasons, desire, ability, and need for change. This predicts increased commitment to the lifestyle change and good clinical outcome	“What makes it important to you to start an exercise program?” “What benefits would come from losing weight?” “Why do you want to quit smoking?”	Remind patient of the benefits of regular exercise and how well it made them feel previously. These measures will help patient become a good role model for their children and allow them to play sports together
7. Develop an action plan	To help the patient develop a plan that is realistic and suitable for their life	Enquire about the next step for the patient. Ask what they think they can do or are willing to do to improve health and make a difference	Motivate patient to follow plan and reiterate the steps agreed, ie, eat more vegetables, avoid fast foods, exercise more, etc

Note: Copyright ©2013. Dove Medical Press. Reproduced with permission from Kalantar-Zadeh K. Patient education for phosphorus management in chronic kidney disease. Patient Prefer Adherence. 2013;7:379–390.¹⁴

Abbreviation: CKD, chronic kidney disease.

Table 4 Factors associated with dietary adherence in adults with ESRD on hemodialysis categorized according to WHO criteria

Study	Patient numbers	Socioeconomic factors	Condition-related factors	Therapy-related factors	Healthcare team and system-related factors	Patient-related factors
Agondi et al^Citation123	117	Higher education level, older age		Shorter dialysis vintage, Dietary knowledge		Positive beliefs regarding the benefits of the diet
Ahrari et al^Citation124	237					Social and family support
Baraz et al, 2010	63	Higher education level, being employed, younger age
Chan et al^Citation17	188	Retired or not working, female gender, older age		Dietary knowledge, short dialysis vintage, diet complexity		Self-efficacy
Clark-Cutaia et al^Citation120	122	Male gender, older age
Dowell et al^Citation125	4			Self-monitoring
Durose et al^Citation126	71		Knowledge of medical complications of dietary nonadherence	Dietary knowledge
Elliott et al^Citation85	95	Minimum of high school education White ethnicity	Better quality of life	Shorter dialysis vintage		Perceived benefits of dietary adherence, self-efficacy
Ford et al^Citation97	70				Intensive patient education
Kara et al^Citation94	160	Older age, being married				Presence of family support; presence of social support
Karavetian and Ghaddar^Citation91	570			Dietary knowledge	Adequate dietitian staffing, experienced renal dietitian
Khalil et al^Citation100	100					Absence of depression
Kugler et al^Citation118	456	Lower education level, female gender, being married				Non-smoking status
Kugler et al^Citation95	916	Female gender, old age		Short dialysis vintage		Family support, non-smoker, non-diabetic status
Lee et al^Citation127	62	Unemployment or non-working status		Shorter dialysis hours per week		Positive attitudes to diet, high residual renal function >300 mL/day
Lindberg et al^Citation34	4,498	Older age		Short dialysis vintage		Higher BMI
Mellon et al^Citation96	50	Older age				Perception that diet fits into lifestyle strategies to manage the diet at social events; positive beliefs and attitudes about the diet
Molaison et al^Citation128	316	Older age, female gender		Self-monitoring
Mok et al^Citation129	50			Long dialysis vintage
Morales López et al^Citation101	34	Adequate finances		Culturally appropriate format of patient education, dietary knowledge	Presence of a dietitian on staff	Presence of family support
O’Connor et al^Citation68	73	Female gender, older age				Adequate psychological coping ability
Pang et al^Citation130	92	Lower family income				Lower comorbid disease burden, presence of social support
Park et al^Citation98	160	Older age				Malnutrition
Poduval et al^Citation131	117	College education		Education about food composition
Sagawa et al^Citation132	10			Self-monitoring
Saran et al^Citation49	7,676	Unemployed, male gender, older age, married		Long dialysis vintage	Presence of a dietitian on staff	Family support, non-smoking status
Sharp et al^Citation133	56				Intensive patient education	Higher self-efficacy
Thomas et al^Citation92	276	White ethnicity, female gender		Dietary knowledge, practical shopping skills		Family support, positive beliefs, and attitudes about the impact of the diet
Tsay et al^Citation134	62			Self-monitoring		High self-efficacy
Welch et al^Citation135	148					Positive beliefs & attitudes about the impact of the diet
Yokoyama et al^Citation136	72				Dialysis staff encouragement	Lower perceived burden of the diet, high self-efficacy, good mental health
Zrinyi et al^Citation99	107	Female gender				High self-efficacy

Note: Adapted from Lambert K, Mullan J, Mansfield K. An integrative review of the methodology and findings regarding dietary adherence in end stage kidney disease. BMC Nephrol. 2017;18:318. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode.¹⁴

Abbreviations: BMI, body mass index; ESRD, end-stage renal disease; WHO, World Health Organization.

Table 5 Strategies to improve control of dietary phosphorus intake and adherence to phosphate binders in ESRD

Patient education	• Introduce education programs, led by nurses or other ancillary healthcare providers, focusing on the:  ◦ physiologic role of phosphate and its presence in different foods  ◦ role of phosphate in ESRD-associated cardiovascular disease  ◦ importance of phosphate binders and their role in lowering serum phosphorus concentrations  ◦ importance of dietary adherence • Involve patients’ families and friends in educational initiatives • Tailor education to patients’ lifestyle, environment, career, ethnicity, cultural background, and socioeconomic status • Educate patients on appropriate food choices and provide training on preparing suitable meals
Patient empowerment	• Introduce initiatives such as the “Phosphate Education Program” which enable patients with hyperphosphatemia to estimate the phosphate content of their meals and adjust their phosphate binder dose accordingly
Improve properties of phosphate binders	• Reduce pill size and burden • Improve palatability • Reduce associated adverse effects • Introduce electronic monitoring devices, which may help patients remember to take their medications and support adherence

Note: Copyright ©2013. ©Covic and Rastogi; licensee BioMed Central Ltd. Reproduced from Covic A, Rastogi A. Hyperphosphatemia in patients with ESRD: assessing the current evidence linking outcomes with treatment adherence. BMC Nephrol. 2013;14(1):153.¹¹

Abbreviation: ESRD, end-stage renal disease.

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