Non-adherence to immunosuppressive medication is a major risk factor for poor clinical outcomes post-transplantation, including graft rejection and graft loss. However, it remains a common issue. Patients can experience side effects that are problematic and there may be a range of other life and psychosocial factors that interfere with treatment regimens. Withstanding such issues, adherence is vital to provide the kidney with the best chance of survival and function. In addition to patient outcomes, ill health resulting from non-adherence is costly to the NHS, since dialysis services are more expensive than those required to support transplantation. The programme of work within this thesis aims to further explore what is known about adherence in adult transplant recipients in order to drive advances in patient support. A series of studies were designed to assess different elements of adherence. This was achieved through: 1) a systematic review of existing research on adherence; 2) retrospectively considering the relationship between pre and post-transplant adherence in haemodialysis (HD) patients who later go onto receive a solid organ; 3) qualitative enquiry of the views and beliefs of clinical staff in relation to the importance of adherence for kidney transplant wait listing; 4) cross-sectional data collection with transplant recipients about treatment beliefs that may help understand behavioural patterns.
The systematic review provided a comprehensive evidence synthesis of literature exploring non-adherence to immunosuppressants among renal transplant recipients. A total of 60 studies were identified as relevant for inclusion. Studies varied in how they measured adherence, including self-report, electronic monitoring, pharmacy refill, blood levels and collateral report, with some studies combining more than one measure in an attempt to increase reliability. The overall non-adherence prevalence ranged across studies from 0.06% to 89.2%, dependent on how adherence was measured and operationalised. Self-report was the most commonly utilised measurement method to assess adherence behaviour. Meta-analysis of 38 studies revealed the pooled prevalence of self-reported non-adherence was 37.6%. The findings highlight a clear lack of consistency in how adherence is measured and defined, with greater guidelines needed across all measurement types.
A retrospective study examined the relationship between clinical measures of pre and post-transplant adherence in a group of patients who moved from HD to receive a transplant. Little previous research has explored if adherence behaviour transfers across modalities. Data was collected for 88 patients about adherence to HD regimens in the six months prior to transplantation, and for one-year post-transplantation following return transfer to the post-transplant clinic from the transplanting centre. Pre-transplant definitions of non-adherence included if patients: on average shortened their dialysis prescription by >10 minutes; shortened by >15 minutes; missed two or more HD sessions; and had mean serum phosphate levels >1.8mmol/l. Post-transplant definitions of non-adherence included: mean tacrolimus levels outside 5-10ng/mL; missed one or more post-transplant clinic appointments. Non-adherence ranged from 25%-42% pre-transplant and 15.9%-22.7% post-transplant dependent on how it was operationalised. There was little relationship between pre-transplant data and post-transplant adherence, with the exception of a significant relationship between pre-transplant phosphate and post-transplant clinic attendance. Patients who had missed one or more transplant clinic appointments had higher mean pre-transplant phosphate levels. Non-adherent patients with high phosphate levels pre-transplant and missed clinic appointments post-transplant were significantly younger.
Qualitative inquiry was used to gain in-depth understanding of how clinicians recognise non-adherence and whether or not pre-transplant adherence features in their decision making when determining if a patient is eligible for transplant listing. Thirty-six staff members who work closely with renal transplant recipients were recruited across two NHS trusts, and interviewed using a semi-structured interview. Staff members included nephrologists, transplant surgeons, registrars, transplant nurse specialists and pharmacists. Interviews were transcribed verbatim and analysed using thematic analysis. Five main themes were extracted on understanding of non-adherence: “Barriers to adherence” (including risk factors and control in ensuring adherence messages are conveyed), “Striving for normality” (in terms of how patients view transplantation as an opportunity for normality and to avoid dialysis) , “Mutuality in maximising patient adherence” (through ensuring patients receive multi-disciplinary care, addressing barriers to adherence, and promoting patient autonomy through education and peer support), “Complexity in shining light on adherence in wait listing” (highlighting subjectivity in the importance of adherence) and “Post-transplant normalization” (with patients less adherent due to perceptions of wellness and a lack of immediate consequences following missed medication doses). Findings demonstrate that clinicians recognise and understand the barriers that patients face with adherence, and work to try and make treatment management easier. Patient understanding and engagement was considered an effective way to promote adherence. Agreement on how adherence is viewed as part of eligibility for wait listing was lacking, with clinicians managing pre-transplant non-adherence in different ways.
A cross-sectional study further elucidated the relationship between self-reported adherence and markers of adherence obtained from clinical data. Additionally, the association between psychological factors, including illness perceptions and beliefs about medicines, with adherence was explored. Self-report measures used included the Medication Adherence Report Scale (MARS-5), Brief Illness Perceptions Questionnaire (Brief IPQ) and the Beliefs about Medicines Questionnaire (BMQ). Open-ended questions were also utilised to investigate how patients conceptualise their post-transplant treatment. Patients were recruited from one renal unit during the post-transplant weekly clinic, with 128 patients completing questionnaires. Findings showed no correlations between clinical data and MARS-5 adherence score. Certain illness perceptions were highlighted as independently predicting adherence behaviour. Perceptions of personal and treatment control were found to increase adherence. Conversely, perceptions of consequences and emotional representation were found to predict lower adherence. Patients reported higher scores on the necessity sub-scale than the concerns sub-scale of the BMQ, indicating they perceive the “benefits” of immunosuppressant medication to outweigh the “costs”, however, the BMQ sub-scales did not significantly predict MARS-5 adherence. The qualitative comments via open-ended questions provided a mixed view towards experience of transplantation. Those reporting positive experiences had feelings of regained life, however, for some, life after transplant did not meet their expectations due to e.g. symptom burden or side effects. The findings point to areas for potential intervention by considering whether illness perceptions in particular should be assessed to signal patients who may struggle to engage with treatment regimens.
In conclusion, it is clear that non-adherence is a prevalent issue among the renal transplant population. This thesis has advanced clear areas of inconsistency in adherence research, alongside chartering new courses for further research and the development of clinical practice. Clearer definitions and measures of adherence are needed to provide greater reliability in reported non-adherence prevalence rates, and to allow for comparisons to be made across studies. A longitudinal follow-up is necessary to explore how and at which point adherence behaviour changes post-transplant. Agreement is needed across clinicians on how to consider the importance of adherence in transplant eligibility for listing. Finally, promoting patient autonomy to self-manage treatment regimens through education and communication is essential to addressing barriers to adherence
