Medication adherence in randomized controlled trials evaluating cardiovascular or mortality outcomes in dialysis patients: A systematic review

Background: Medication non-adherence is common among renal dialysis patients. High degrees of non-adherence in randomized controlled trials (RCTs) can lead to failure to detect a true treatment effect. Cardio-protective pharmacological interventions have shown no consistent benefit in RCTs involving dialysis patients. Whether non-adherence contributes to this lack of efficacy is unknown. We aimed to investigate how medication adherence and drug discontinuation were assessed, reported and addressed in RCTs, evaluating cardiovascular or mortality outcomes in dialysis patients. Methods: Electronic database searches were performed in MEDLINE, EMBASE & Cochrane CENTRAL for RCTs published between 2005-2015, evaluating self-administered medications, in adult dialysis patients, which reported clinical cardiovascular or mortality endpoints, as primary or secondary outcomes. Study characteristics, outcomes, methods of measuring and reporting adherence, and data on study drug discontinuation were analyzed. Results: Of the 642 RCTs in dialysis patients, 22 trials (12 placebo controlled), which included 19,322 patients, were eligible. The trialed pharmacological interventions included anti-hypertensives, phosphate binders, lipid-lowering therapy, cardio-vascular medications, homocysteine lowering therapy, fish oil and calcimimetics. Medication adherence was reported in five trials with a mean of 81% (range: 65-92%) in the intervention arm and 84.5% (range: 82-87%) in the control arm. All the trials that reported adherence yielded negative study outcomes for the intervention. Study-drug discontinuation was reported in 21 trials (mean 33.2%; 95% CI, 22.0 to 44.5, in intervention and 28.8%; 95% CI, 16.8 to 40.8, in control). Trials with more than 20% study drug discontinuation, more often yielded negative study outcomes (p = 0.018). Non-adherence was included as a contributor to drug discontinuation in some studies, but the causes of discontinuation were not reported consistently between studies, and non-adherence was listed under different categories, thereby potentiating the misclassification of adherence. Conclusions: Reporting of medication adherence and study-drug discontinuation in RCTs investigating cardiovascular or mortality endpoints in dialysis patients are inconsistent, making it difficult to compare studies and evaluate their impact on outcomes. Recommendations for consistent reporting of non-adherence and causes of drug discontinuation in RCTs will therefore help to assess their impact on clinical outcomes

Evaluating the contributors to treatment nonadherence in patients with kidney failure and adherence improvement strategies: implications for clinical practice

Kidney failure (KF) is an important chronic disease with immense global-health impact due to the excessive mortality, morbidity and treatment costs. Its highly complex therapy demands a high level of self-management, with strict dietary, fluid, dialysis and medication adherence. Nonadherence to all aspects of therapy is common, yet under-recognised. Strategies to improve treatment adherence in KF have not been widely implemented nor well established. This doctoral thesis, presented as a thesis by compilation, evaluates treatment adherence in KF patients. The overarching aim of the thesis was to explore the issues associated with nonadherence in patients with KF on dialysis, focusing on health literacy (HL), cognitive function and depression and analysing adherence improvement strategies. A combination of empirical studies and systematic and narrative literature reviews, using concepts from the WHO adherence framework, were undertaken to achieve these aims

Incidence and factors associated with geographical relocation in patients receiving renal replacement therapy

BACKGROUND: Renal replacement therapy (RRT) places a burden on patients, and geographical relocation for easier access to healthcare facilities is a necessity for some. Incidence and factors associated with relocation has not been comprehensively examined at a national level. We aimed to determine proportion, incidence, characteristics of RRT patients who relocate and relocation rate by remoteness of residence and dialysis modality. METHODS: Retrospective cohort analysis using Australian and New Zealand Dialysis and Transplant Registry to examine RRT patients in Australia from January 2005 to December 2015. Relocation incidence was calculated for remoteness of residence and RRT modality as rate per 100 patient years. Factors associated with relocation were examined using competing risk regression models with death as a competing event. RESULTS: Of 24,676 incident patients on RRT, 5888 (23.9%) relocated with a median time of 1.6 years [IQR 0.7-3.4] years. Relocation incidence was 7.9 per 100 patient years and increased from major cities to very remote regions (7.2 to 48.8 per 100 patient years respectively, p \u3c 0.001). Remoteness of residence was associated with geographical relocation in competing risk analysis especially in remote (SHR 1.20, 95%CI 1.01, 1.41 p = 0.034) and very remote regions (SHR 3.51 95% 3.05, 4.04 p \u3c 0.001). Aboriginal or Torres Strait Islander ethnicity, compared to Caucasian, was independently associated with relocation (SHR 1.18, 95% CI 1.06,1.31, p = 0.002) while transplant patients were less likely to relocate compared to haemodialysis patients (HR 0.37, 95%CI 0.34, 0.39, p \u3c 0.001). CONCLUSIONS: Relocation in patients receiving RRT is associated with remoteness of residence, RRT modality and ethnicity. Reasons for relocation and its impact on patient wellbeing and outcome should be further explored

AngioJetTM rheolytic thrombectomy induced intravascular haemolysis leading to Acute Kidney Injury requiring Dialysis

Background: AngioJetTM rheolytic thrombectomy has been used in the treatment of deep vein thrombosis (DVT) to prevent post-thrombotic syndrome. Though not widely appreciated, it has the potential to cause intravascular haemolysis. Report: A 37 year old man with no previous medical history presented to his GP with a three week history of progressive right upper limb swelling. Doppler imaging confirmed right upper limb DVT and CT scan demonstrated thoracic outlet syndrome. The patient underwent AngioJetTM thrombectomy followed by IV heparin infusion. Successful revascularisation of the occluded vein was achieved. Overnight he developed haematuria, which was initially attributed to IV heparin. Urinalysis however revealed no red cells or casts. Apart from an Hb drop from 134 to 117 his blood profile and blood film showed no abnormality. He subsequently developed progressive oliguria with marked oedema and acute kidney injury (AKI). His creatinine peaked at 1070umol/l at 96 hours post procedure and he was started on intermittent dialysis. He remained dialysis dependent for 6 days. Ultrasound imaging excluded urinary obstruction. Autoimmune and vasculitic serology were negative. Intravascular haemolysis and haemoglobinuria was confirmed by raised LDH (1714u/L) and low haptoglobin (<0.1units). Direct Coomb’s test, Cold agglutinin test and paroxysmal nocturnal haemoglobinuria screen were negative. The patient’s renal function normalised over 3 months. Conclusions: The likely cause of this man’s AKI is heme pigment nephropathy from intra-vascular haemolysis. Increased awareness of this condition may allow early identification and intervention to reduce the risk of renal injury from AngioJetTM associated haemolysis

Comparison of health literacy profile of patients with end-stage kidney disease on dialysis versus non-dialysis chronic kidney disease and the influencing factors: a cross-sectional study

Objectives: Lower health literacy (HL) is associated with poor outcomes in patients with kidney disease. Since HL matches the patient\u27s competencies with the complexities of the care package, the level of HL sufficient in earlier stages of chronic kidney disease (CKD) may be inadequate for patients with end-stage kidney disease (ESKD) on dialysis. We aimed to analyse the HL profile of patients with ESKD and non-dialysis CKD and examine if there were significant associations with covariates which could be targeted to address HL deficits, thereby improving patient outcomes. Design and setting: Cross-sectional study of patients with CKD and ESKD from a single Australian health district. Methods: We assessed the HL profile of 114 patients with CKD and 109 patients with ESKD using a 44-item multidomain Health Literacy Questionnaire (HLQ) and examined its association with demographic factors (age, gender, race), smoking, income, education, comorbidities, carer status, cognitive function and depression. Using multivariable logistic regression models, HL profiles of patients with CKD and ESKD were evaluated after adjusting for covariates. Results: Patients with ESKD had similar demographics and educational levels compared with patients with CKD. ESKD had significantly higher frequency of vascular disease, cognitive impairment and depression. Patients with ESKD had better HL scores for the social support domain (37.1% vs 19.5% in higher HLQ4 tertile, p=0.004), whereas all other HL domains including engagement with healthcare providers were comparable to CKD. Depression was independently associated with nearly all of the HL domains (HLQ1: OR 2.6, p=0.030; HLQ2: OR 7.9, p=\u3c0.001; HLQ3: OR 7.6, p\u3c0.001; HLQ4: OR 3.5, p=0.010; HLQ5: OR 8.9, p=0.001; HLQ6: OR 3.9, p=0.002; HLQ7: OR 4.8, p=0.001; HLQ8: OR 5.3, p=0.001) and education with HL domains relevant to processing health-related information (HLQ8: OR 2.6, p=0.008; HLQ9: OR 2.5, p=0.006). Conclusions: Despite very frequent interactions with health systems, patients with ESKD on dialysis did not have higher HL in engagement with health providers and most other HL domains, compared with patients with CKD. Strategies promoting patient-provider engagement and managing depression which strongly associates with lower HL may address the impact of HL deficits and favourably modify clinical outcomes in renal patients

Strategies to improve dietary, fluid, dialysis or medication adherence in patients with end stage kidney disease on dialysis: A systematic review and meta-analysis of randomized intervention trials

BACKGROUND:In patients with end stage kidney disease (ESKD) on dialysis, treatment non-adherence is common and results in poor health outcomes. However, the clinical benefits of interventions to improve adherence in dialysis patients are difficult to evaluate since trialled interventions and reported outcomes are highly diverse/ heterogeneous. This review summarizes existing literature on randomized controlled trials (RCTs) evaluating adherence interventions in ESKD patients focusing on the intervention category, outcome efficacy and persistence of benefit beyond the intervention. METHODS:We performed electronic database searches in Medline, Embase & Cochrane CENTRAL upto 1st July 2018 for RCTs evaluating interventions to improve diet, fluid, medication or dialysis adherence in ESKD patients. Study characteristics including category of interventions, outcomes, efficacy and follow-up were assessed. Meta-analysis was used to compute pooled estimates of the effects on the commonest reported outcome measures. RESULTS:From 1311 citations, we included 36 RCTs (13 cluster-randomized trials), recruiting a total of 3510 dialysis patients (mean age 55.1 ± 5.8 years, males 58.1%). Overall risk of bias was 'high' for 24 and of 'some concern' for 12 studies. Most interventions (33 trials, 92%) addressed patient related factors, and included educational/cognitive (N = 11), behavioural / counselling (N = 4), psychological/affective (N = 4) interventions or a combination (N = 14) of the above. A majority of (28/36) RCTs showed improvement in some reported outcomes. Surrogate measures like changes in phosphate (N = 19) and inter-dialytic weight gain (N = 15) were the most common reported outcomes and both showed significant improvement in the meta-analysis. Sixteen trials reported follow-up (1-12 months) beyond intervention and the benefits waned or were absent in nine trials within 12 months post-intervention. CONCLUSIONS:Interventions to improve treatment adherence result in modest short-term benefits in surrogate outcome measures in dialysis patients, but significant improvements in trial design and outcome reporting are warranted to identify strategies that would achieve meaningful and sustainable clinical benefits. LIMITATIONS:Poor methodological quality of trials. Frequent use of surrogate outcomes measures. Low certainly of evidence

Treatment adherence in clinical trials evaluating cardiovascular or mortality outcomes in dialysis patients: a systematic review

Abstract of an oral presentation at the 51st Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology, 7-9 September 2015, National Convention Centre, Canberra, Australia

What is the health literacy of renal patients? Results of a cross sectional study

Abstract of a poster that presented at the 50th Annual Scientific Meeting of the Australian and New Zealand Society of Nephrology, 25-27 August 2014, Melbourne Convention and Exhibition Centre Melbourne, Australia