Patient non-adherence is a significant, multi-dimensional challenge to securing the best long-term treatment outcomes in hyperphosphatemia of CKD. In a 2010 survey-based study , 76% of nephrologists and 63% of dialysis staff thought non-compliance with phosphate binders was the main reason for poor control of phosphate in patients.
In this article we question:
- How prevalent is non-adherence in CKD-related hyperphosphatemia?
- What is the impact of this non-adherence?
How prevalent is non-adherence?
Available data is scarce, but it appears reasonable to assume that non-adherence to phosphate binders is not lower than the 40% to 50% non-adherence rates seen across other chronic treatment regimens.
A systematic review  of the prevalence of non-adherence was published in BMC Nephrology in 2008. The study identified the mean rate of non-adherence as 51%, although there was wide variation in the reported rates, ranging from 22% to 74% of patients. This variation was in part due to how the source studies defined and measured adherence. Mean rates of non-adherence were higher when patients were assessed through serum phosphorus levels rather than through self-report, at 58% versus 31%.
The review only identified one demographic predictor of non-adherence: young age. By contrast, psychosocial variables, such as patients’ beliefs about medication, social support, and their personality characteristics, were more likely to be associated with non-adherence.
Highlighting the fundamental lack of available evidence on the topic, the review only found 13 studies in a 40-year period between 1967 and 2006 that reported rates of non-adherence to phosphate binders.
A subsequent 2010 cross-sectional cohort study  of 165 Spanish hemodialysis patients by Arenas et al. found 40% of patients non-adherent to their prescribed drugs, with 21% of patients admitting non-adherence to phosphate binders.
Given the lack of specific data, a useful way to validate these findings is through comparison with non-adherence data from other diseases. As referenced in a WHO report, Adherence to Long-term Therapies: Evidence for Action, a number of reviews have found that, “in developed countries, adherence among patients suffering chronic diseases averages only 50%”. This would appear to provide support for the 50% mean range observed in the hyperphosphatemia studies.
What are the impacts of this non-compliance?
There is also limited data available on the impact of non-compliance on treatment outcomes in hyperphosphatemia, as well as on the cost-effectiveness of treatment.
One recent study  of 121 hemodialysis patients taking phosphate binders showed that serum phosphorus levels were significantly higher in patients that did not comply with their treatment regimen versus patients who did. Adherence was assessed in this instance via a patient survey, rather than by serum phosphorus levels.
In addition, this paper suggested that non-adherent patients were more likely to have phosphorus levels >5.5 mg/dL, a widely-used upper boundary of the target range in CKD stage 5 patients.
While the association between adherence and phosphorous control is not surprising, further research is needed to confirm the association. To illustrate this point, another recent study  was unable to demonstrate any relationship between therapy adherence and serum phosphorus levels. The authors of this paper, which also shed light on the association between pill burden and adherence, suggested that physicians were responding to uncontrolled serum phosphorous by prescribing a larger number of phosphate binders to compensate for non-adherence.
In fact, this hints at another impact of non-adherence: escalating costs. Given that cost increases  associated with implementing recent treatment guidelines can be significant, additional studies could also be performed to quantify the cost of non-adherence. Furthermore, estimates for non-adherence rates could also be factored into the cost-effectiveness models of available treatments.
In summary: the available evidence, while scarce, points to a 40%-50% non-adherence rate and an association between non-adherence and poorer treatment outcomes.
In order to improve adherence in hyperphosphatemia, understanding the cause of poor adherence is the first important step in alleviating the situation. In our next blog post (see article May 16th) we will explore some of the factors that are responsible for poor patient compliance in hyperphosphatemia of CKD patients.
What are your experiences of patient adherence to phosphate binders? Let us know by commenting below.
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