Adherence to Therapy: Burden, Complexity, and Perception.

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The lack of adherence to prescribed therapy is a major issue in patients with kidney disease. For instance, non-adherence occurs in a significant proportion of patients with resistant hypertension with or without chronic kidney disease (CKD)., In dialysis patients, the lack of adherence also explains an uncontrolled hyperphosphatemia and hyperparathyroidism., In renal transplantation, non-adherence to immunosuppressive therapies can lead to serious complications, such as acute rejection and graft loss. Studying and understanding non-adherence is thus of importance. Different factors are known to be associated with non-adherence. Among them, pill burden and polypharmacy are well-identified risk factors. The issue of pill burden is well illustrated in the study by Marienne et al. in this issue. Of interest, the authors studied pill burden before and until 1 year after renal transplantation. In this retrospective study, the same patients from 1 center in France were followed before and after transplantation. A comparison with the French registry of dialysis and transplantation showed that the patients included were representative of the CKD population in that country.

In addition to the pill burden, the authors also studied the complexity of the treatment, based on a recognized score, the Medication Regimen Complexity Index. This score varies with the number of drugs prescribed and is based on 3 components: dosage form or administration route, dosing frequency, and additional instructions concerning administration. The authors convincingly show that both the pill burden and the complexity of the treatment are higher after than before transplantation. Also, the authors clearly show that the class of drugs varies from dialysis to transplantation (immunosuppressive drugs becoming the first class of drug after transplantation). The study remains, however, descriptive, and we do not know whether this higher pill burden or complexity will lead to the same degree of non-adherence in patients before and after transplantation. The perception of the patient (but also of the physician) regarding the relevance of the drug is probably important but is difficult to capture in the context of a retrospective study.

The perception of the importance of the drug can be easily illustrated by some examples in which both the patient and the physician will be involved. Indeed, one could reasonably hypothesize that, at the same level of complexity, adherence to immunosuppressive drugs is higher in a transplant recipient than adherence to phosphate binders when the same patient was undergoing dialysis. Immunosuppressive drugs are certainly considered essential to the patients who will keep in mind the risk of returning to dialysis, whereas phosphate binders are prescribed to control hyperphosphatemia, which will have very few direct impacts on patients’ symptoms. In addition, the physician will surely explain (and insist on) the risk of non-adherence to immunosuppression to their patients, probably in a more intense manner than the risk of phosphate binding, for which a definitive evidence of efficacy on clinically relevant outcomes is still lacking. Regardless of the shared perception between physicians and patients, it remains likely that decreasing the pill burden and the complexity of treatment could certainly help to improve adherence of the patients (even if strictly speaking the impact of decreasing complexity on adherence still needs to be proven). As reminded by the authors, a strategy of “polypills” is interesting (even if not always easy to implement), as is a strategy of “deprescribing.”

The potential role of education, social support, or both, and the intervention of pharmacists dedicated to patients with CKD are probably also of interest in all aspects of our specialty., Other straightforward ideas deserved to be explored. First, the concept of medication reconciliation must not be neglected. Albeit obvious and fundamental with regard to medication safety, the notion of medication reconciliation has been well shown to be insufficient in patients with complex conditions such as CKD, especially during care transitions. Medication conciliation is always the first step to improve adherence to therapies. Likewise, in dialysis patients, the directly observed therapy—that is, a drug given directly by the nurse during the dialysis session—should be promoted when possible. We have shown, for example, that directly observed therapy with native vitamin D (cholecalciferol, 25,000 units once a week) was associated with better vitamin D 25-OH concentrations. In the same context, therapies dedicated to the treatment of secondary hyperparathyroidism can be prescribed orally for home use or orally or intravenously during the dialysis session (calcitriol or either cinacalcet or etelcalcetide). The better results obtained in the real life with intermittent therapies is due, at least in part, to the better adherence associated with a directly observed therapy strategy. In transplantation, simple strategies can help to improve adherence —for example, health apps on smartphones, which have been shown to reduce variability in tacrolimus trough concentrations.

Although improving adherence to drug regimens by patients with CKD remains a true and important challenge, the mechanisms underlying adherence and the impact of specific interventions still need to be further clarified.

Disclosure

All the authors declared no competing interests.