Exploring the Agreement Between Self-Reported Medication Adherence and Pharmacy Refill-Based Measures in Patients with Kidney Disease.

Aim: To assess the quantitative and categorical agreement between two methods of measuring medication adherence: pharmacy refill-based medication possession rates and self-reported medication adherence scale. Background: Categorisation of adherence metrics using empirical cut-off scores can lead to misclassification, which can be overcome by expressing adherence as a continuous variable. Pharmacy refill-based adherence can be reported as actual rates, but the validity of expressing self-reported medication adherence scores as a continuous variable to reflect adherence is unknown and its quantitative agreement with refill-based adherence rates untested. Methods: Patients with kidney disease, including dialysis patients, from Illawarra Shoalhaven region of New South Wales, Australia were recruited between January 2015 and June 2016 to this cross-sectional study. Medication adherence was assessed using the self-reported Morisky Medication Adherence Scale (MMAS) and two pharmacy refill-based measures, Medication Possession Ratio (MPR) and Proportion of Days Covered (PDC) for antihypertensives and cardiometabolic drugs. Categorical and quantitative agreement between self-reported adherence and pharmacy refill-based adherence were assessed using tests of trend, analysis of covariance (ANCOVA), Cohen's kappa and Bland-Altman analysis. Results: We recruited 113 patients. There was a significant declining trend of MPR (p < 0.001) and PDC (<0.001 for antihypertensives, p = 0.004 for cardiometabolic) scores among categories with worsening MMAS adherence. Adjusted ANCOVA showed significant association between self-report and pharmacy refill-based adherence (p < 0.001). Weighted Cohen's kappa statistics showed fair agreement between the self-report and pharmacy refill-based categories. Bland-Altman's analysis showed less than 5% of cases were outside the limits of agreement (-0.36 to 0.27) and the bias for MMAS was negative (-0.05 to -0.09), indicating MMAS did not overestimate adherence. Conclusion: There is modest agreement between pharmacy refill-based measures and self-report MMAS measures when assessed categorically or quantitatively. Assessing adherence as a continuous variable should be considered to overcome the challenges associated with categorization of adherence based on arbitrary thresholds.

Elevated renal resistive index is independently predicted by older age, but not by the presence of chronic kidney disease: a retrospective cohort study.

BACKGROUND: Renal resistive index (RRI), which reflects intrarenal arterial impedance, is routinely measured when undertaking renal Doppler ultrasonography (RDU). Increased RRI has been suggested to reflect renal parenchymal disease and imply risk of kidney disease progression. But this has been disputed and extra-renal haemodynamic factors rather than intra-renal factors have been proposed to determine RRI. AIMS: To investigate the relationship between elevated RRI and presence of chronic kidney disease (CKD), and examine whether elevated RRI at baseline is associated with decline in estimated glomerular filtration rate (eGFR) on follow up. METHODS: This retrospective observational study examined the association of elevated RRI (>0.7) with the presence of CKD (eGFR < 60 mL/min for >3 months), demographic and clinical factors in multivariable models. We also examined the effect of elevated RRI on eGFR decline on follow up using mixed models. RESULTS: Of the 346 patients undergoing RDU (median age 69.7 years; 46.2% male), 180 had elevated RRI. There was a strong inverse association between RRI and eGFR at baseline, 1 and 2 years (rho = -0.53, -0.51, -0.53, all P < 001). Elevated RRI was independently predicted by older age (odds ratio 3.29; 95% confidence interval 2.25-4.8; P < 0.001) and diabetes (odds ratio 2.65; 95% confidence interval 1.21-5.80; P = 0.015), but not CKD using multivariate logistic regression. Decline of eGFR was not different between RRI categories on follow up. CONCLUSION: Elevated RRI was predicted by older age and diabetes, but not by the presence of CKD. Baseline RRI was not associated with eGFR decline.

Changes in measures of cognitive function in patients with end-stage kidney disease on dialysis and the effect of dialysis vintage: A longitudinal cohort study.

INTRODUCTION: Prevalence of cognitive impairment increases with worsening severity of chronic kidney disease (CKD) and majority of end-stage kidney disease (ESKD) patients on dialysis have cognitive impairment. Trends of cognitive function (CF) in this population are less well known with published studies reporting conflicting results. METHODS: We assessed CF in a cohort of non-dialysis CKD and ESKD patients undergoing dialysis using modified mini-mental state examination (3MS), trail-making test (TMT-A & B) scores and Stroop task, and evaluated demographics, comorbidities and depression using Beck depression inventory at baseline. We repeated tests of CF and depression ≥ 1-year after baseline in both groups and compared change scores in CF and depression between ESKD/ CKD sub-groups. Among ESKD patients we compared change scores between patients with dialysis vintage of <1-year and >1-year. Analysis of covariance was used to adjust for the effect of age on these change scores. RESULTS: At baseline (N = 211), compared to CKD (N = 108), ESKD (N = 103) patients had significantly worse CF based on 3MS and TMT-A & B scores, and depression scores. On follow-up (N = 160) 3MS scores, especially the memory subscale significantly improved in ESKD, but worsened in CKD, with no significant changes in TMT A /TMT-B, or depression scores after adjusting for age. Among ESKD patients, 3MS, especially memory subscale improved in patients with dialysis vintage <1-year compared to >1-year. The 51 patients who discontinued after baseline assessment had worse baseline CF scores suggesting differential attrition. CONCLUSION: Though baseline cognitive scores were worse in ESKD patients on dialysis, compared to CKD, their 3MS, especially memory subscale improved on follow-up. Among ESKD patients, the improvement was significant only in patients who have been on dialysis for less than one-year which may indicate a beneficial effect of clearance of uraemic toxins. Differential attrition of study subjects may have impacted the observed results.

Breaking the adherence barriers: Strategies to improve treatment adherence in dialysis patients.

Nonadherence to therapy (dietary/fluid restrictions, medications, and dialysis treatment), is common in patients with end-stage kidney disease (ESKD) undergoing dialysis. It is associated with a higher risk of mortality and adverse outcomes. Clinical trials evaluating adherence improvement interventions have largely addressed patient-related factors by employing educational/cognitive, counselling/behavioral, psychological strategies, or combinations thereof. A major barrier to progress in addressing ESKD-related adherence is the difficulty in comparing these trials due to the highly diverse nature of interventions and adherence outcomes. Surrogate outcomes like changes in inter-dialysis weight gain or phosphate levels are frequently used without adjusting for confounders, with the potential for biased efficacy estimates. A majority of trials reported improvement in some adherence measures, but some of the same studies showed no improvement in other adherence markers, questioning the validity of outcome measurement. Among the interventions, cognitive/behavioral strategies, combination strategies, and individually delivered interventions may have some advantages. Relapse of nonadherence, which is common on follow-up, should be managed to sustain long-term adherence. Technology-based interventions hold great future potential for addressing ESKD nonadherence. Streamlining intervention strategies and standardizing outcome measures in future clinical trials will provide reliable guidance to manage nonadherence effectively, which may improve clinical outcomes in dialysis 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.

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.