Multicenter, prospective, interventional study in HD patients with follow-up at 0, 3, 6, and 12 months.

Adult patients undergoing HD treatment for at least 3 months prior to inclusion who had suboptimal P control were included, defined as serum P levels > 5.5 mg/dl (> 1.78 mmol/l) at the start of the study, or controlled P levels (< 5.5 mg/dl) but requiring high doses of phosphate binders, defined as > 7 pills/day.

Additionally, patients had to be able to comply with the study protocol, which involved following the instructions for phosphate binder administration (without changing the type of binder throughout the study) and attending follow-up visits, as well as completing the required questionnaires. Finally, all participating patients signed an informed consent form to participate in the study.

The study included an intervention group and a control group. Patients were randomly assigned to one of these 2 groups. Patient allocation to the study groups was performed in a randomized manner by research personnel external to the participating centers, with no involvement in patient recruitment or in the application of the intervention at each center. Allocation was consecutive and balanced, ensuring a similar number of patients in the intervention and control groups at each center. No losses occurred after initial assignment. Patients in the intervention group received educational tools specifically designed to improve patient self-care and autonomy, enabling them to assume a more active role in managing their phosphate binder treatment, while the control group did not receive any additional educational intervention and continued with usual management of their treatment.

The educational intervention consisted of a single structured initial interview, conducted by the patient's attending nephrologist following a prior training session aimed at the participating professionals. During this interview, the basic principles of P content and bioavailability in foods were explained, as well as the use of the tool to adjust binder administration according to intake.

No systematic follow-up educational reinforcement program was established, and no other healthcare professionals (nurses or dietitians) were involved in the direct application of the intervention, with the aim of evaluating its feasibility and reproducibility in routine clinical practice in HD units.

As part of the educational tool, patients had access to an explanatory video, which they could view autonomously as many times as they deemed necessary, facilitating the repetition and consolidation of the content.

Patients assigned to the control group continued with the usual P management at each center, without receiving additional structured educational intervention. This management was carried out according to the usual clinical practice of each HD unit, with potential inter-center variations in aspects such as the availability of dietary support or the type of phosphate binder prescribed.

Both cohorts were followed for the same period and the results were compared in terms of P control, number of pills and dose of phosphate binders, and treatment adherence between the 2 groups.

Various demographic, clinical, and treatment variables were collected. Regarding demographic variables, basic data such as age, sex, CKD etiology, time since HD initiation, type of dialysis used, as well as the presence of diabetes mellitus and vascular access type (arteriovenous fistula or catheter) were recorded.

Laboratory variables were measured at several time points during the study (baseline, 1, 3, 6, and 12 months) and included parameters such as mean Kt/V or KT index, serum P, calcium, parathyroid hormone (PTH), vitamin D, albumin, C-reactive protein, and hemoglobin. These variables allowed the evaluation of P control and other key factors in the treatment of HD patients. All laboratory determinations were performed on pre-dialysis samples corresponding to the short interdialytic period, following the standard procedures of each center and in accordance with standard clinical practice in HD.

Data on the pharmacological treatment patients were receiving were also collected, including the administration of vitamin D (cholecalciferol, calcifediol), calcimimetics (etelcalcetide or cinacalcet), paricalcitol, calcitriol, alfacalcidol, rocaltrol, and denosumab. Likewise, erythropoietin (EPO) doses and the daily amount of phosphate binders, as well as the frequency of their use and the type of binder used, were recorded.

The variables used to analyze the effectiveness of the model included serum P levels, which were used to evaluate P control in patients. Secondary variables included the number of pills and daily milligrams of phosphate binder taken. Monitoring of phosphate binder use was performed through a "last week reminder," which patients completed by recording daily doses and the foods with which they took the binders.

Overall pharmacological treatment compliance was measured using the Simplified Medication Adherence Questionnaire (SMAQ), a validated tool for assessing pharmacological adherence in patients with chronic diseases, including CKD and the HD population.9,10 The SMAQ consists of 6 questions that allow patients to be classified as adherent or non-adherent based on their responses. Adherence to phosphate binder treatment was assessed using the SMAQ questionnaire at each scheduled visit (0, 3, 6, and 12 months). Given its dichotomous nature, any response indicative of non-compliance classified the patient as non-adherent.

The response alternatives are dichotomous; any response in the direction of non-compliance is considered non-adherence to treatment.

A training session was held for the participating nephrologists, addressing communication skills and instructions for using the tool. The importance of the different sources of P (organic and inorganic) and their bioavailability was emphasized, in order to train nephrologists to convey this information to patients and empower them in managing their disease.

Each nephrologist conducted an interview with the patients, during which the tool was delivered and explained. This tool included figures designed for individualized treatment and to promote patient empowerment, providing guidance on how to take phosphate binders in relation to the foods consumed, adjusting doses according to the type of meal, and including intermediate snacks (Fig. 1).

Fig. 1.

Images of the materials delivered to patients. A) Information from the A4-sized magnet. B) Image of the foldable accordion card (business card size).

The educational intervention was based on a tool developed specifically for this study, called "Patient Empowerment in Phosphorus Control (Empower-PHOS)," aimed at facilitating the understanding of P content in foods and the autonomous adjustment of binders according to intake. The "Empower-PHOS" tool consisted of a series of materials with illustrations about the P content of different foods and practical information serving as a guide on how to dose binders according to intake at each meal, adjusting the dose in relation to the amount and type of foods consumed during both main meals and intermediate snacks. The materials delivered to patients consisted of: (1) an A4-sized magnet with information to optimize the administration of the prescribed binders (Fig. 2A) (2) a business card-sized foldable accordion card with synthesized information (for the patient to always carry with them when eating outside the home) (Fig. 2B), and (3) an explanatory video of the materials.

Fig. 2.

Flowchart of patient inclusion, randomization, and follow-up. Of the 122 patients included and randomized, all were evaluated at 3 months. The number of patients evaluated decreased progressively at 6 and 12 months due to follow-up losses inherent to the hemodialysis population. The number of patients with complete data available for analysis at 12 months is indicated in each group.

The satisfaction assessment was carried out through structured questionnaires, which included items on overall perception, usefulness of the materials, and care experience, differentiated for patients and healthcare professionals.

The study was approved by the Ethics Committee of Fundación Jiménez Díaz (reference code: PIC007-22_FJD). All patients signed written informed consent before inclusion.

Sample size calculation: According to published data, approximately 75% of HD patients have low adherence to phosphate binders. It was estimated that the educational intervention could reduce the proportion of non-adherent patients by 20%. Considering a significance level of 5%, a power of 80%, and an estimated loss of 15%, it was calculated that 174 patients (87 per group) would be needed to detect differences between groups. The final number of included patients was conditioned by the actual availability of participants at the centers.

Qualitative variables were expressed as absolute frequencies and percentages and compared using the chi-squared test. The distribution of quantitative variables was assessed using the Shapiro-Wilk test. Quantitative variables were described as mean and standard deviation (SD) if they followed a normal distribution, or as median and interquartile range (IQR: 25th–75th percentile) otherwise. For baseline comparison between the control and intervention groups, Student's t-test for independent samples or the Mann–Whitney U test for independent samples was used for non-normally distributed data.

Cochran's Q test was applied to assess possible changes in treatment adherence across the 4 study time points (0, 3, 6, and 12 months). Comparisons at 0, 3, 6, and 12 months were performed using Student's t-test for paired samples or the Wilcoxon signed-rank test, as appropriate. These tests were applied both to the intra-group analysis (intervention and control) and to the subgroups defined by treatment adherence within each group (according to the second SMAQ questionnaire measurement in each pairwise comparison).

Due to the pragmatic nature of the study and the progressive loss of follow-up during the 6- and 12-month evaluations, an analysis based on intra-group pairwise comparisons at each time point was chosen, in order to use the available information from patients evaluated at each visit. Although linear mixed models could have allowed a more complete longitudinal analysis, their application was limited by the variability in the number of patients available at the different follow-up time points.

A p value ≤ 0.05 was considered statistically significant. The analysis was performed using IBM SPSS® Statistics v29.0, and graphical representations were created with Microsoft Excel® 2021.

In the intervention group, P levels decreased significantly at 3 months (p ≤ 0.001) and at 12 months (p = 0.010), without changes in the number of pills or daily dose (Table 2). In the control group, there were no significant changes in P; only a reduction in the number of pills (p = 0.029) and dose (p = 0.021) was observed at 12 months. Additionally, the percentage of patients with serum P levels < 5.5 mg/dl was analyzed at each time interval. In the control group, the percentages of patients with controlled P were 34.5% at baseline, 37.0% at 3 months, 38.2% at 6 months, and 40.0% at 12 months. In the intervention group, these percentages were 31.3% at baseline, 50.0% at 3 months, 45.3% at 6 months, and 51.7% at 12 months. Overall, the intervention group showed a higher percentage of patients with controlled serum P (<5.5 mg/dl) at all time points after study initiation.

Although the main analysis focused on intra-group changes throughout follow-up, no statistically significant inter-group differences were observed in absolute serum P values or total binder dose at the different time points. Nevertheless, serum P decreases without concomitant dose increases were more consistent in the intervention group.

Adherence assessed by the SMAQ questionnaire did not show significant changes throughout follow-up in either group (Cochran's Q: control group p = 0.153; intervention group p = 0.112). The proportion of adherent and non-adherent patients remained stable across all time point evaluations, with no relevant differences between groups.

Adherence did not show significant changes throughout the study in either group (Cochran's Q: control p = 0.153; intervention p = 0.112).

Both groups showed a significant reduction in P, more marked and sustained in the intervention group (Table 3). In the intervention group, the median baseline value went from 5.7 to 4.8 mg/dl at 3 months (p = 0.005); 4.8 ± 1.9 mg/dl at 6 months (p = 0.013); 5.3 ± 1.1 at 12 months (p = 0.004). In the control group, the median went from 5.7 to 5.1 mg/dl at 3 months (p = 0.004); from 6.0 ± 1.5 to 5.0 ± 1.2 at 12 months (p = 0.023).

Among adherent patients in the intervention group, there were no changes in the number or dose of binders, whereas in the control group both parameters decreased significantly at 12 months (Table 3).

Only the intervention group showed a significant reduction in P at 12 months (6.4 ± 1.2 → 5.8 ± 1.2 mg/dl; p = 0.015). In the control group, P levels remained elevated without significant changes at any time point (Table 3).

Regarding treatment, among non-adherent patients in the intervention group, there was a significant reduction between 0 and 3 months in both the number of pills (p = 0.043) and the dose (p = 0.037), remaining stable thereafter. In the control group, there were no changes.

Overall, adherent patients in both groups had lower P levels than non-adherent patients, although differences in binder use were more pronounced in the control group.

The overall patient rating was high, with a mean of 8.2/10, participation 8.5/10, and willingness to recommend the intervention also 8.5/10. The materials were perceived as easy to use (4/5) and useful for remembering and understanding the information (3.6–3.8/5).

Responses were obtained from 20 of 27 professionals (74%), who rated the strategy as effective (3.9/5) and easy to implement (4/5), although they rated its impact on improving adherence more modestly (2.8/5). Overall satisfaction with the intervention was high (8.6/10). In qualitative comments, professionals noted initial difficulties in adjusting the dose and explaining to the patient how to match binders to meals; however, once the regimen was internalized, the simplification of the process proved beneficial. They also emphasized that the intervention is especially useful for reinforcing and consolidating adherence in already-adherent patients, but less effective for modifying behaviors in those with low baseline adherence.